Evaluating the predictive validity of MCAT scores across diverse applicant groups

PURPOSE: To examine the predictive validity of MCAT scores, alone and in combination with other preadmission data, for medical students grouped by race/ethnicity and sex. METHOD: This study included two samples: 1,109 students who entered in 1992 any of the 14 medical schools participating in the MCAT Predictive Validity Study; and all 11,279 students who entered medical school in 1992 and took the USMLE Step 1 in June 1994. Criterion measures included each student's cumulative GPA in the first two years of medical school and his or her pass/fail status on Step 1. Differential predictive validity was examined by comparing prediction errors across racial/ethnic and sex groups. For cumulative GPA; residuals were compared, and for Step 1, classification errors were studied. RESULTS: The patterns of prediction errors observed across the groups indicated that, on average, (1) no difference between the sexes in prediction errors was evident; (2) performances of the three racial/ethnic minority groups tended to be overpredicted, with significant findings for Asians and Hispanics; and (3) Caucasians' performance tended to be underpredicted, although the magnitude of this underprediction was quite small. When USMLE Step 1 scores were the criterion for success in medical school, the majority of errors were overprediction errors. CONCLUSION: The authors caution that although MCAT scores, alone and in combination with undergraduate GPA, are good predictors of medical school performance, they are not perfect. The authors encourage future research exploring additional predictor variables, such as diligence, motivation, communication skills, study habits, and other relevant characteristics. Similarly, they indicate that high grades and Step 1 scores are not the only indicators of success in the medical profession and call for studies examining other important qualities, such as integrity, interpersonal skills, capacity for caring, willingness to commit to lifelong learning, and desire to serve in underserved areas.     

Crossover study of the haematological effects and pharmacokinetics of glycosylated and non-glycosylated G-CSF in healthy volunteers

A cross-over study of glycosylated and non-glycosylated G-CSF was performed in 20 healthy male volunteers to compare the effects of the different forms of G-CSF, the extent of inter-individual progenitor cell mobilization and to determine whether any differences observed were related to the serum concentrations of G-CSF attained. The peak WBC achieved during 6 d of G-CSF administration at a dose of 5 microg/kg/d was significantly higher with the glycosylated than the non-glycosylated product (P = 0.02) as was the peak level of granulocyte-monocyte colony forming cells (GM-CFC) (P=0.03). The average GM-CFC count on days 5, 6 and 7 was 28% higher with the glycosylated product (P=0.003). Serum concentrations of G-CSF achieved were significantly higher with the non-glycosylated G-CSF, however, suggesting that the difference in bio-efficacy was not due to a difference in G-CSF stability. Marked inter-individual variation in progenitor mobilization was observed, but this was not related to serum G-CSF levels. The G-CSF concentrations on day 6 were approximately one third of those on day 1, with both forms of G-CSF.     

Acute pulmonary toxicity of urban particulate matter and ozone

We have investigated the acute lung toxicity of urban particulate matter in interaction with ozone. Rats were exposed for 4 hours to clean air, ozone (0.8 ppm), the urban dust EHC-93 (5 mg/m3 or 50 mg/m3), or ozone in combination with urban dust. The animals were returned to clean air for 32 hours and then injected (intraperitoneally) with [3H]thymidine to label proliferating cells and killed after 90 minutes. The lungs were fixed by inflation, embedded in glycol methacrylate, and processed for light microscopy autoradiography. Cell labeling was low in bronchioles (0.14 +/- 0.04%) and parenchyma (0.13 +/- 0.02%) of air control animals. Inhalation of EHC-93 alone did not induce cell labeling. Ozone alone increased (P < 0.05) cell labeling (bronchioles, 0.42 +/- 0.16%; parenchyma, 0.57 +/- 0.21%), in line with an acute reparative cell proliferation. The effects of ozone were clearly potentiated by co-exposure with either the low (3.31 +/- 0.31%; 0.99 +/- 0.18%) or the high (4.45 +/- 0.51%; 1.47 +/- 0.18%) concentrations of urban dust (ozone X EHC-93, P < 0.05). Cellular changes were most notable in the epithelia of terminal bronchioles and alveolar ducts and did not distribute to the distal parenchyma. Enhanced DNA synthesis indicates that particulate matter from ambient air can exacerbate epithelial lesions in the lungs. This may extend beyond air pollutant interactions, such as to effects of inhaled particles in the lungs of compromised individuals.     

Phase I trial of continuous infusion flavopiridol, a novel cyclin-dependent kinase inhibitor, in patients with refractory neoplasms

PURPOSE: We conducted a phase I trial of the cyclin-dependent kinase inhibitor, flavopiridol (National Service Center [NSC] 649890), to determine the maximum-tolerated dose (MTD), toxicity profile, and pharmacology of flavopiridol given as a 72-hour infusion every 2 weeks. PATIENTS AND METHODS: Seventy-six patients with refractory malignancies with prior disease progression were treated with flavopiridol, with first-cycle pharmacokinetic sampling. RESULTS: Forty-nine patients defined our first MTD, 50 mg/m2/d x 3 with dose-limiting toxicity (DLT) of secretory diarrhea at 62.5 mg/kg/d x 3. Subsequent patients received antidiarrheal prophylaxis (ADP) to define a second MTD, 78 mg/m2/d x 3 with DLT of hypotension at 98 mg/m2/d x 3. Other toxicities included a proinflammatory syndrome with alterations in acute-phase reactants, particularly at doses >50 mg/ m2/d x 3, which in some patients prevented chronic therapy every 2 weeks. In some patients, ADP was not successful, requiring dose-deescalation. Although approximately 70% of patients displayed predictable flavopiridol pharmacology, we observed unexpected interpatient variability and postinfusion peaks in approximately 30% of cases. At the two MTDs, we achieved a mean plasma flavopiridol concentration of 271 nM (50 mg/m2/d x 3) and 344 nM (78 mg/m2/d x 3), respectively. One partial response in a patient with renal cancer and minor responses (n=3) in patients with non-Hodgkin's lymphoma, colon, and renal cancer occurred. CONCLUSION: The MTD of infusional flavopiridol is 50 mg/m2/d x 3 with dose-limiting secretory diarrhea at 62.5 mg/m2/d x 3. With ADP, 78 mg/m2/d x 3 was the MTD, with dose-limiting hypotension at 98 mg/m2/d x 3. Based on chronic tolerability, 50 mg/m2/d x 3 is the recommended phase II dose without ADP. Antitumor effect was observed in certain patients with renal, prostate, and colon cancer, and non-Hodgkin's lymphoma. Concentrations of flavopiridol (200 to 400 nM) needed for cyclin-dependent kinase inhibition in preclinical models were achieved safely.     

Interleukin-10 inhibits the in vitro proliferation of human activated leukemic CD5+ B-cells

Umbilical cord blood mononuclear cells isolated by density centrifugation are contaminated by erythrocytes and nucleated erythroid precursors which may exceed 50% of the total cell population, and thus interfere with phenotypic, functional and mRNA analyses. Lysis with hypotonic ammonium chloride can overcome this problem, but interferes with lysosomal function and should be avoided when cell preparations are intended for functional studies. The aim of this study was to develop a technique for removing erythroid cells from cord blood mononuclear cell preparations that would be as effective as ammonium chloride lysis but would not affect cellular function. This paper describes a method using 10F7, a mouse monoclonal antibody against human glycophorin A, and magnetic beads coated with anti-mouse immunoglobulin. The population of cord blood mononuclear cells recovered using this technique was of high purity, good yield and viability, and the cells responded appropriately to stimulation in vitro. To maximise cost-effectiveness, purification with magnetic beads could be performed after two density separations to reduce the quantity of beads required.     

Clinical utility of long-term enalapril/diltiazem ER in stage 3-4 essential hypertension. Long-term Use of Enalapril/Diltiazem ER in Stage 3-4 Hypertension Group

The use of angiotensin converting enzyme inhibitors and calcium channel blockers, as monotherapies and in combination, is common in the management of hypertension. Clinical studies have documented the augmentation of blood pressure reduction when these agents are combined compared with the individual agents, in short-term studies. In the present investigation, 93 patients with stage 3-4 essential hypertension, who successfully completed a short-term double-blind study, participated in a 40-week open-label treatment phase. The patients were maintained on their previous doses of enalapril/diltiazem ER (E/D) with or without additional antihypertensive medications. Doses of medication could be adjusted as necessary for blood pressure control. Of the 93 patients, 68% were male and 82% were white; they averaged 52.7 years of age and had a baseline mean sitting blood pressure (SiBP) of 167/111 mmHg. The use of E/D alone (n = 14) reduced mean SiBP by 14.5/14.4 mmHg from baseline, whereas the use of E/ D with other agents (n = 79) decreased it by 27/20.5 mmHg from baseline. E/D alone or in combination with other drugs was well-tolerated, and no serious adverse events were noted. This long-term open-label study demonstrated that the E/D combination alone or with the addition of other antihypertensive drugs was effective, safe, and well-tolerated after prolonged administration.     

Cost minimization analysis of various treatment options for surgical stage I endometrial carcinoma

A rapid bioluminometric technique for real-time detection of known single-base changes is presented. The concept relies on the measurement of the difference in primer extension efficiency by a DNA polymerase of a matched over a mismatched 3' terminal. The rate of the DNA polymerase-catalyzed primer extension is measured by an enzymatic luminometric inorganic pyrophosphate (PPi) detection assay (ELIDA) (P. Nyrén (1987) Anal. Biochem. 167, 235-238). The PPi formed in the polymerization reaction is converted to ATP by ATP sulfurylase and the ATP production is continuously monitored by the firefly luciferase. In the single-base detection assay, immobilized single-stranded DNA fragments are used as template. Two detection primers differing with one base at the 3' end are designed, one precisely complementary to the nonmutated DNA sequence and the other precisely complementary to the mutated DNA sequence. The primers are hybridized with the 3'-termini over the base of interest and the primer extension rates are, after incubation with DNA polymerase and deoxynucleotides, measured with the ELIDA. We show that the relative mismatch extension efficiency is strongly decreased by substituting the alpha-thiotriphosphate analog for the next correct natural deoxynucleotide after the 3'-mismatch termini. The possibility of using the technique for studies of mismatch extension kinetics for two polymerases lacking exonucleolytic activity is shown.     

Serum creatinine concentration and risk of cardiovascular disease: a possible marker for increased risk of stroke

BACKGROUND AND PURPOSE: Elevated serum creatinine has been associated with increased mortality in hypertensive persons, the elderly, and patients with myocardial infarction or stroke in whom cardiovascular disease is the major cause of death. We have examined the relationship between serum creatinine concentration and the risk of major ischemic heart disease and stroke events and all-cause mortality in a general population of middle-aged men. METHODS: We present a prospective study of middle-aged men (aged 40 to 59 years) drawn from 24 British towns who have been followed up for an average of 14.75 years. Data on serum creatinine were available for 7690 men in whom there were 287 major stroke events, 967 major ischemic heart disease events, and 1259 deaths from all causes during follow-up. RESULTS: The median serum creatinine concentration was 98 micromol/L (95% range, 76 to 129 micromol/L). Stroke risk was significantly increased at levels above 116 micromol/L (90th percentile) even after adjustment for a wide range of cardiovascular risk factors (relative risk [RR], 1.6; 95% CI, 1.1 to 2.1; > 116 micromol/L versus the rest). Risk of a major ischemic heart disease event was significantly increased at or above 130 micromol/L (97.5 percentile), but this was attenuated after adjustment (RR, 1.2; 95% CI, 0.8 to 1.7; > or = 130 micromol/L versus the rest). There was a weak but significant positive association between diastolic blood pressure and creatinine concentration. However, elevated creatinine concentration (> or = 116 micromol/L) was associated with a significant increase in stroke in both normotensive and hypertensive men. All-cause mortality and overall cardiovascular mortality were significantly increased only above the 97.5 percentile, and no significant association was seen with cancer or other noncardiovascular mortality. CONCLUSIONS: A high serum creatinine concentration within the normal range is a marker for increased risk of cerebrovascular disease in both normotensive and hypertensive subjects. These findings support the evidence indicating that subtle impairment of renal function is a factor for increased risk of stroke and suggest mechanisms in the pathogenesis of stroke that warrant further investigation.     

Refined mapping and YAC contig construction of the X-linked cleft palate and ankyloglossia locus (CPX) including the proximal X-Y homology breakpoint within Xq21.3

STUDY OBJECTIVES: To investigate topographical changes in electroencephalographic (EEG) frequencies and spectral power density in relation to different surgical procedures (abdominal hysterectomy versus mastectomy) during steady-state isoflurane-nitrous oxide (N2O) anesthesia. DESIGN: Prospective, nonrandomized, open study. SETTING: University hospital. PATIENTS: 34 ASA status I and II patients scheduled for elective abdominal hysterectomy or mastectomy. INTERVENTIONS: 12 patients were studied without surgery (Group I, control). 22 patients were studied for the first 14 minutes following skin incision during hysterectomy (Group 2, n = 11) or mastectomy (Group 3, n = 11). MEASUREMENTS AND MAIN RESULTS: Anesthesia was maintained with 0.6% isoflurane in 66% N2O in oxygen (O2). EEG was recorded via 17 channels followed by calculation of spectral power densities in selected frequency bands for each recording site. In addition, heart rate, mean arterial pressure (MAP), end-tidal carbon dioxide tensions, and isoflurane concentration were recorded. Total observation time was 20 minutes in all groups. At baseline, EEG variables were comparable in all groups. The EEG demonstrated slow wave activity superimposed with alpha waves. Start of surgery resulted in increases of slower waves and decreases in alpha activity. In both surgical groups, these EEG changes were most pronounced at frontal recording sites (p < 0.05) with differences in the frequency content. In Group 2 (hysterectomy), delta-activity became dominant, whereas in Group 3 (mastectomy), a shift to theta waves was observed. During surgery MAP was increased by 40% (Group 2; p < 0.05) and 21% (Group 3; p < 0.05), respectively. CONCLUSIONS: These results show that specific surgical procedures may induce EEG slow wave activity to a different degree. The EEG response varied in relation to the surgical procedure and/or the intensity of noxious stimulation. Mastectomy resulted in the appearance of theta activity whereas, during laparotomy, the EEG frequency content was shifted to delta waves. The topographical analysis indicates spatial inhomogeneities in the EEG responses with a dominance at frontal areas. From this findings, it may be concluded that the electrode montage used for intraoperative EEG recordings has to be carefully selected.