Effect of ambulatory utilization review on referrals from generalists to specialists

We studied whether ambulatory utilization review (UR) alters how many patients internal medicine residents refer to sub-specialists, and whether the effect persists without reinforcement. We compared referral rates of residents from a firm that held UR meetings (intervention firm residents, n = 20) with those of residents from a firm that did not (control firm residents, n = 21). We then compared referral rates of 17 intervention firm residents while they were participating in UR with their rates after not participating for at least 4 weeks. Intervention firm residents submitted 30% fewer referrals than control firm residents (9% vs 13%, p = .05). However, the effect was short-lived; after 4 weeks without UR, intervention firm resident referral rates were similar to control firm referral rates.     

Correcting the bias of clerkship timing on academic performance

OBJECTIVES: To document the time-of-year bias in National Board of Medical Examiners subject examination (NBME) scores in a third-year pediatrics clerkship and to develop a grading method that neutralizes the bias. DESIGN: Interventional modeling of final grades. SETTING: University-based medical school. SUBJECTS AND METHODS: During each of the past 3 academic years, we conducted six 2-month pediatric clerkships for third-year students. To counter the time-of-year bias, NBME scores, clinical evaluations, and departmental examination scores for the current rotation were pooled with those from the rotations from the same time of year during the previous 2 years. Final grades for the current rotation were determined by cutoff points derived from that entire 3-year pool. We analyzed this approach by testing the time-of-year effects on NBME scores, clinical evaluations, and final grades while maintaining step 1 of the US Medical Licensing Examination as a preclinical baseline control. RESULTS: The scores for step 1 of the US Medical Licensing Examination did not differ significantly by time of year. Clinical evaluations and NBME scores showed significant upward trends as the academic year progressed. By contrast, according to design, final grades showed no significant time-of-year trend. CONCLUSIONS: Our results support previous reports of significant improvements in NBME scores across the academic year. Our method of computing final grades corrects for this time-of-year bias by judging students only in relation to those who took the rotation at the same time of year. It is our belief that the prevalence and significance of the time-of-year trend warrants such an adjustment in grading to help minimize the academic disadvantage faced by students early in their clinical training.     

Selective convective brain cooling during normothermic cardiopulmonary bypass in dogs

BACKGROUND: Neurologic complications, primarily resulting from ischemic insults, represent the leading cause of morbidity and disability, and the second most common source of death, after cardiac operations. Previous studies have reported that increases (as occur during the rewarming phase of cardiopulmonary bypass [CPB]) or decreases in brain temperature of a mere 0.5 degrees to 2 degrees C can significantly worsen or improve, respectively, postischemic neurologic outcome. The purpose of the present study was to evaluate a novel approach of selectively cooling the brain during hypothermic CPB and subsequent rewarming. METHODS: Sixteen dogs were anesthetized with either intravenous pentobarbital or inhaled halothane (n = 8 per group). Normocapnia (alpha stat technique) and a blood pressure near 75 mm Hg were maintained. Temperatures were monitored by placing thermistors in the esophagus (i.e., core), parietal epidural space, and brain parenchyma at depths of 1 and 2 cm beneath the dura. During CPB, core temperature was actively cycled from 38 degrees C to 28 degrees C, and then returned to 38 degrees C. Forced air pericranial cooling (air temperature of approximately 13 degrees C) was initiated simultaneous with the onset of CPB, and maintained throughout the bypass period. Brain-to-core temperature gradients were calculated by subtracting the core temperature from regional brain temperatures. RESULTS: In halothane-anesthetized dogs, brain temperatures at all monitoring sites were significantly less than core during all phases of CPB, with one exception (2 cm during systemic cooling). Brain cooling was most prominent during and after systemic rewarming. For example, during systemic rewarming, average temperatures in the parietal epidural space, and 1 and 2 cm beneath the dura, were 3.3 degrees +/- 1.3 degrees C (mean +/- standard deviation), 3.2+/-1.4 degrees C, and 1.6 degrees +/-1.0 degrees C, cooler than the core, respectively. Similar trends, but of a greater magnitude, were noted in pentobarbital-anesthetized dogs. For example, during systemic rewarming, corresponding brain temperatures were 6.5 degrees +/-1.7 degrees C, 6.3 degrees +/-1.6 degrees C, and 4.2+/-1.3 degrees C cooler than the core, respectively. CONCLUSIONS: The magnitude of selective brain cooling observed in both study groups typically exceeded the 0.5 degrees to 2.0 degrees C change previously reported to modulate ischemic injury, and was most prominent during the latter phases of CPB. When compared with previous research from our laboratory, application of cold forced air to the cranial surface resulted in brain temperatures that were cooler than those observed during hypothermic CPB without pericranial cooling. On the basis of the assumption that similar beneficial brain temperature changes can be induced in humans, we speculate that selective convective brain cooling may enable clinicians to improve neurologic outcome after hypothermic CPB.     

The min K channel underlies the cardiac potassium current IKs and mediates species-specific responses to protein kinase C

A clone encoding the guinea pig (gp) min K potassium channel was isolated and expressed in Xenopus oocytes. The currents, gpIsK, exhibit many of the electrophysiological and pharmacological properties characteristic of gpIKs, the slow component of the delayed rectifier potassium conductance in guinea pig cardiac myocytes. Depolarizing commands evoke outward potassium currents that activate slowly, with time constants on the order of seconds. The currents are blocked by the class III antiarrhythmic compound clofilium but not by the sotalol derivative E4031 or low concentrations of lanthanum. Like IKs in guinea pig myocytes, gpIsK is modulated by stimulation of protein kinase A and protein kinase C (PKC). In contrast to rat and mouse IsK, which are decreased upon stimulation of PKC, myocyte IK and gpIsK in oocytes are increased after PKC stimulation. Substitution of an asparagine residue at position 102 by serine (N102S), the residue found in the analogous position of the mouse and rat min K proteins, results in decreased gpIsK in response to PKC stimulation. These results support the hypothesis that the min K protein underlies the slow component of the delayed rectifier potassium current in ventricular myocytes and account for the species-specific responses to stimulation of PKC.     

Allelic diversity in the merozoite surface protein-1 and epidemiology of multiple-clone Plasmodium falciparum infections in northern Tanzania

Allelic diversity in the merozoite surface protein-1 (MSP-1) of Plasmodium falciparum, a major malaria vaccine candidate, was examined in clinical isolates from holoendemic northern Tanzania. The variable blocks 2, 4a, 4b, 6, and 10 of the MSP-1 gene were typed by allelic type-specific polymerase chain reaction. Twenty-four possible MSP-1 gene types were defined as unique combinations of allelic types detected in each variable block. Thirteen gene types were identified, and 187 P. falciparum populations were fully typed among 79 isolates. In contrast with recent findings in Vietnam, we were unable to detect nonrandom associations between allelic types in the typed variable blocks. Most patients (60%) harbored more than 1 genetically distinct parasite population (average: 2.37 populations per isolate) and, in 1 patient, 6 different versions of this single-copy gene were found. Statistical analysis suggests that parasites carrying different MSP-1 gene types are not independently distributed in the host population. The epidemiological consequences of these findings are discussed.     

Impaired tumorigenicity of IL-4-producing murine neuroblastoma cells in immunodeficient nude mice

OBJECTIVE: Our purpose was to evaluate the clinical utility of serum uric acid measurements in the hypertensive diseases of pregnancy. STUDY DESIGN: We performed a nested case-control study to assess the clinical utility of serum uric acid measurements in women with hypertensive diseases of pregnancy. We identified 344 women who had serum uric acid measurements at term and categorized them into five diagnostic groups according to definitions of hypertensive diseases in pregnancy published by the National Working Group on Hypertension in Pregnancy: transient hypertension of pregnancy (n = 69), preeclampsia (n = 130), chronic hypertension (n = 23), chronic hypertension with superimposed preeclampsia (n = 29), and normal (n = 93). We compared the mean uric acid concentration for each group with use of a one-way analysis of variance and Scheffe's post hoc test and calculated the sensitivities and specificities in diagnosing preeclampsia as well as the likelihood ratios for serum uric acid values of 5.5, 6.0, and 6.5 mg/dl. We also examined the correlation between serum uric acid levels and several clinical outcome measures in women with hypertensive diseases of pregnancy. RESULTS: The mean serum uric acid values for women with preeclampsia (6.2 +/- 1.4 mg/dl) and transient hypertension (5.6 +/- 1.7 mg/dl) were significantly higher than those of controls (4.3 +/- 0.8 mg/dl, p < 0.05). The difference in mean serum uric acid values between women with chronic hypertension (4.9 +/- 1.0 mg/dl) and superimposed preeclampsia (5.8 +/- 1.4 mg/dl) were not statistically significant. The likelihood ratio of having preeclampsia with a serum uric acid value of 5.5 mg/dl was 1.41 in gestational hypertension of pregnancy and 2.5 in chronic hypertension. With use of a receiver-operator characteristic curve, we were unable to identify a serum uric acid value that could be used to differentiate various hypertensive diseases of pregnancy. There was a weak correlation between serum uric acid values and several clinical outcome measures of preeclampsia (r = 0.06 to 0.26). CONCLUSION: Although mean serum uric acid values are elevated in women with preeclampsia, the clinical utility of serum uric acid values in differentiating various hypertensive diseases of pregnancy appears to be limited. In the setting of chronic hypertension, however, a serum uric acid level of > or = 5.5 mg/dl could identify women with an increased likelihood of having superimposed preeclampsia.     

Surface properties of TiFe and TiFe-Nb 6.8 at.% electrodes in aqueous solution

Even at ambient pressure and temperature TiFe and TiFe-Nb 6.8 at.% compounds display their outstanding abilities for absorbing hydrogen when cathodically polarized in an aqueous solution. Electrochemical reaction is also highly activated on electrodes made of these intermetallic compounds. This paper describes the results of electrochemical measurement and the surface properties of both TiFe and TiFe-Nb 6.8 at.% electrodes in comparison with those obtained using TiNi_n and TiCo_n (n = 1, 2, 3), emphasizing catalytic activity for the reaction of hydrogen evolution. It was concluded that the electrochemically active site of TiFe or TiFe-Nb 6.8 at.% electrode surface could be formed only after a specified area of the electrode had been covered with hydrogen of one or a few atomic layers. At the same time, this site acts as an entrance and exit for hydrogen into and out of the electrode.     

Oxidation of mixed copper-iron sulfide

. A rectangular plate of mixed copper-iron sulfide composed of bornite (Cu₅FeS₄) and troilite (FeS) was oxidized in an O₂-Ar mixed gas stream at 1023 to 1123 K. At the start of the oxidation, iron was preferentially oxidized with the rapid formation of a dense Fe₃O₄ layer of about 10 μm thickness on the sample surface, without the evolution of SO₂ gas. Following this reaction, layers of both Fe₃O₄ and Fe₂O₃ grew on the sulfide surface in accordance with the parabolic rate law. The diffusion of iron through the oxide layers was assumed to control the oxidation rate during this stage. The effect of oxygen partial pressure on the parabolic rate constants was minor and an apparent activation energy of 126 kJ/mol was obtained. During the later stages of the reaction, when the sulfur activity in the inner sulfide core increased, the oxidation proceeded irregularly to the interior of the remaining sulfide with the formation of a porous oxide and the evolution of gaseous SO2. The remaining sulfide core was found to be a mixture of bornite (Cu₅FeS₄) and djurleite (Cu_1.96S). H. TSUKADA, former Graduate Student at Kyoto University     

Purification and properties of human N-acetylgalactosamine-6-sulfate sulfatase

1. Human N-acetylgalactosamine-6-sulfate sulfatase (EC 3.1.6.-) from human placenta has been purified more than 3000-fold by gel filtration, ion-exchange and substrate affinity chromatography. The enzyme has a molecular weight of 90 000 by gel filtration chromatography and 85 000 by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis. Enzyme purified from cultured human skin fibroblasts has similar properties. 2. The tritium-labeled chrondroitin 6-sulfate trisaccharide N-acetylgalactosamine 6-sulfate-(beta, 1-4)-glucuronic acid-(beta, 1-3(-N-acetyl[1-3H]galactosaminitol 6-sulfate as substrate demonstrated a Km of 0.12 mM at pH 4.5. Sulfate was hydrolyzed only from the non-reducing terminal of this disulfated trisaccharide. Hyaluronic acid, dermatan sulfate, chondroitin 4-sulfate, heparin and chondroitin 6-sulfate tetrasaccharide were slightly inhibitory, whereas 6-sulfated pentasaccharides and heptasaccharides were strongly inhibitory. The enzyme dose not hydrolyze sulfate from N-acetylglucosamine 6-sulfate.