Structure of the 3'-hairpin of the TYMV pseudoknot: preformation in RNA folding

The solution structure of an RNA-hairpin present in the pseudoknot, which is found at the 3'-terminus of turnip yellow mosaic virus genomic RNA, has been solved by nuclear magnetic resonance spectroscopy. The loop, which contains the sequence 5'-GGGUCA-3', was found to be highly structured and, contrary to expectations, does not attain its stability through GA or GC base pair formation but by triple interactions between the tilted adenosine and the minor groove sides of the first two guanosines. Interestingly, a very similar conformation was found for the cognate pseudoknot, implying that the 3'-hairpin is preformed for folding into a pseudoknotted structure. These findings suggest a mechanism of 'predetermined-fit' as a principle in RNA folding.     

Dynamic axial external fixation in the surgical treatment of tibia vara

Osteotomy is the well-established treatment of Blount's disease (tibia vara), although the types of fixation used vary considerably. The use of dynamic axial external fixation to stabilize osteotomies for tibia vara until solid union occurs without the use of supplemental casting has not been reported by other authors. From 1985 until the present, we have used osteotomy with dynamic axial external fixation as treatment of 31 tibiae in 23 patients. All osteotomies healed and there was no postoperative loss of correction. There was an average correction of 20 degrees between the pre- and postoperative mechanical axis. Advantages of dynamic axial external fixation include ease of application, adjustability, early weight bearing, the ability to lengthen the extremity, and no second operation for removal of hardware. Based on our results, we believe that dynamic axial external fixation is an excellent form of osteotomy stabilization in the surgical treatment of tibia vara.     

Neonatology radiology casebook. Tracheal agenesis

BACKGROUND: Biliary tract diseases are frequent in heart transplant recipients, with significant morbidity and mortality. Since the first presentation of gallstones in this population is often acute cholecystitis, asymptomatic cholelithiasis should not be considered benign. PATIENTS AND METHODS: We retrospectively reviewed 18 heart transplant recipients who underwent cholecystectomy from January 1991 to June 1997. We intentionally chose to perform a straightforward open procedure when acute cholecystitis was suspected (3 patients). A laparoscopic cholecystectomy was performed in all the other cases (15 patients) without conversion to open procedure. CONCLUSION: Since no significant complications were observed in our patients, we believe that transplant recipients with cholelithiasis should undergo laparoscopic cholecystectomy in their posttransplantation course regardless of the symptomatic status of their biliary tract.     

Knowledge and attitudes of health-care providers toward cancer pain management: a comparison of physicians, nurses, and pharmacists in the state of New Hampshire

The knowledge and attitudes toward cancer pain management of physicians, nurses, and pharmacists in the state of New Hampshire were examined through the use of a statewide survey. Many of the providers who completed the survey, and thus indicated that they treated patients with cancer pain on a regular basis, were not pain or oncology specialists. Most of these providers were quite well informed about the fundamentals of cancer pain management. Approximately 90% of providers in all three groups were not concerned about addiction among cancer patients. Yet, there was a small percentage of providers who responded in less than optimal ways to items dealing with opioid pharmacology, pain assessment, and the importance of pain relief. Comparison of responses among provider groups indicated that nurses were the most knowledgeable and pharmacists the least knowledgeable about pain assessment. Physicians were the most knowledgeable regarding opioid pharmacology but seemed the least committed to providing optimal pain relief. Further analysis identified a small group of physicians that included a disproportionately high percentage of family practitioners and surgeons who consistently responded in less than optimal ways to items dealing with the importance of pain relief. The results of this study indicate a continuing need for broad-based educational programs in cancer pain management and for new initiatives focused on practitioners who see relatively few cancer patients and may have difficulty accessing traditional educational programs.     

The threat of funding cuts for graduate medical education: survey of decision makers

OBJECTIVE: To assess the potential actions of medical school deans, graduate medical education (GME) committee chairs, and hospital chief executive officers (CEOs) regarding future funding reductions for residency training. Specifically, institutions with emergency medicine (EM) residencies were surveyed to see whether EM training was disproportionally at risk for reductions. METHODS: An anonymous 2-page survey was used. Ninety-eight EM residency programs were identified using the American Medical Association Graduate Medical Education Directory 1994-95. Seventy deans, 102 GME chairs, and 97 hospital CEOs were identified. The survey posed a hypothetical 25% forced reduction in residency positions and asked the decision makers for their responses. Options included: 1) proportional reductions of training positions from all residencies, 2) proportional reductions in either primary care or specialty residency positions, or 3) reduction or elimination of specific training programs. The survey asked for a first and second choice of residencies to be reduced or eliminated from an alphabetical list of 17. The survey elicited explanations for each program reduction. RESULTS: 200 (74%) of 269 surveys were returned. Eighty-four responders selected specific residencies to be reduced or eliminated. EM was selected 8 times, making EM the seventh most vulnerable residency to be targeted for reductions. The decision makers who selected proportional reductions chose to reduce across all residencies 32 times, among only the specialty residencies 129 times, and among only the primary care residencies 3 times. CONCLUSIONS: In the setting of anticipated residency cuts, favored proportional reductions in specialty residencies would likely affect EM training. However, most GME decision makers with an existing EM residency program do not consider the EM residency a top choice to be reduced or eliminated.     

The Homothorax homeoprotein activates the nuclear localization of another homeoprotein, extradenticle, and suppresses eye development in Drosophila

The Extradenticle (Exd) protein in Drosophila acts as a cofactor to homeotic proteins. Its nuclear localization is regulated. We report the cloning of the Drosophila homothorax (hth) gene, a homolog of the mouse Meis1 proto-oncogene that has a homeobox related to that of exd. Comparison with Meis1 finds two regions of high homology: a novel MH domain and the homeodomain. In imaginal discs, hth expression coincides with nuclear Exd. hth and exd also have virtually identical, mutant clonal phenotypes in adults. These results suggest that hth and exd function in the same pathway. We show that hth acts upstream of exd and is required and sufficient for Exd protein nuclear localization. We also show that hth and exd are both negative regulators of eye development; their mutant clones caused ectopic eye formation. Targeted expression of hth, but not of exd, in the eye disc abolished eye development completely. We suggest that hth acts with exd to delimit the eye field and prevent inappropriate eye development.     

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.