Report from the Council of Emergency Medicine Residency Directors subcommittee on graduate medical education funding: effects of decreased medicare support.

INTRODUCTION: Recent changes by the Health Care Financing Administration (HCFA) have resulted in decreased Medicare support for emergency medicine (EM) residencies. OBJECTIVE: To determine the effects of reduced graduate medical education (GME) funding support on residency size, resident rotations, and support for a fourth postgraduate year (PGY) of training and for residents with previous training. METHODS: A 36-question survey was developed by the Council of Emergency Medicine Residency Directors (CORD) committee on GME funding and sent to all 122 EM program directors (PDs). Responses were collected by the Society for Academic Emergency Medicine (SAEM) office and blinded with respect to the institution. RESULTS: Of 122 programs, 109 (89%) responded, of which 78 were PGY 1-3 programs, 19 were PGY 2-4, and 12 were PGY 1-4. The PDs were asked specifically whether there were changes in program size due to changes in Medicare reimbursement. Although few programs (12%) decreased their size or planned to decrease their size, 39% had discussions regarding decreasing their size. Thirty percent of the PDs responded that other programs at their institution had already decreased their size; 26% of the PDs had problems with financing outside rotations; and 24% had a decrease in off-service residents in their emergency departments (EDs). Only seven (6%) of programs paid residents from practice plan dollars, while most (82%) were fully supported by federal GME funding. Nearly all four-year programs (97%) received full resident salary support from their institutions and 77% of programs accept residents with previous training. CONCLUSIONS: Nearly all EM programs are fully supported by their institutions, including the fourth postgraduate year. Most programs take residents with previous training. Although few programs have reduced their size, many are discussing this. Many programs have had difficulty with funding off-service rotations and many have had decreased numbers of off-service residents in their EDs. Recent GME funding changes have had adverse effects on EM residency programs.

The glucocorticoid receptor interacting protein 1 (GRIP1) localizes in discrete nuclear foci that associate with ND10 bodies and are enriched in components of the 26S proteasome.

The glucocorticoid receptor interacting protein-1 (GRIP1) is a member of the steroid receptor coactivator (SRC) family of transcriptional regulators. Green fluorescent protein (GFP) fusions were made to full-length GRIP1, and a series of GRIP1 mutants lacking the defined regulatory regions and the intracellular distribution of these proteins was studied in HeLa cells. The distribution of GRIP1 was complex, ranging from diffuse nucleoplasmic to discrete intranuclear foci. Formation of these foci was dependent on the C-terminal region of GRIP1, which contains the two characterized transcriptional activation domains, AD1 and AD2. A subpopulation of GRIP1 foci associate with ND10s, small nuclear bodies that contain several proteins including PML, SP100, DAXX, and CREB-binding protein (CBP). Association with the ND10s is dependent on the AD1 of GRIP1, a region of the protein previously described as a CBP-interacting domain. The GRIP1 foci are enriched in components of the 26S proteasome, including the core 20S proteasome, PA28alpha, and ubiquitin. In addition, the irreversible proteasome inhibitor lactacystin induced an increase in the total fluorescence intensity of the GFP-GRIP1 expressing cells, demonstrating that GRIP1 is degraded by the proteasome. These findings suggest the intriguing possibility that degradation of GRIP1 by the 26S proteasome may be a key component of its regulation.

Using the hospital Intranet to meet competency standards for nurses.

Regulatory agencies increasingly require hospitals to provide evidence of employee compliance with mandated competencies. This article provides information on the innovative use of Intranet-delivered computer-based training as an effective and efficient method of providing and documenting training to meet regulatory requirements. The authors discuss the advantages and disadvantages of Intranet-based instructional modules, instruction on developing Intranet-based modules, and an example of a healthcare system that is effectively using intranet-based modules for competency training.

Characterization of transiently and constitutively expressed progesterone receptors: evidence for two functional states.

Activated steroid receptors induce chromatin remodeling events in the promoters of some target genes. We previously reported that transiently expressed progesterone receptor (PR) cannot activate mouse mammary tumor virus (MMTV) promoter when it adopts the form of ordered chromatin. However, when expressed continuously, the PR acquires this ability. In this study we explored whether this gain of function occurs through alterations in nucleoprotein structure at the MMTV promoter or through changes in receptor status. We observed no major structural differences at the MMTV promoter in the presence of constitutively expressed PR and found its mechanism of activation to be very similar to that of the glucocorticoid receptor (GR). However, a systematic comparison of the functional behavior of the transiently and constitutively expressed PR elucidated significant differences. The transiently expressed PR is activated in the absence of ligand by cAMP and by components in FBS and has significantly increased sensitivity to progestins. In contrast, the constitutively expressed PR is refractory to activation by cAMP and serum and has normal sensitivity to its ligand. In addition, while the PR is localized to the nucleus in both cases, a significant fraction of the transiently expressed PR is tightly bound to the nucleus even in the absence of ligand, while the majority of constitutively expressed PR is not. These results strongly suggest that the PR undergoes processing in the cell subsequent to its initial expression and that this processing is important for various aspects of its function, including its ability to productively interact with target genes that require chromatin remodeling for activation.

Management of skin trauma.

The majority of skin trauma incidents cause minor injury that can be treated effectively in the outpatient setting. A new approach to the closure of skin lacerations using tissue adhesive is presented and the current management of abrasions, blisters, burns, skin tears, and subungual hematomas are reviewed. An overview of wound dressings is provided to assist in obtaining the optimal wound-healing environment.

The glucocorticoid receptor: rapid exchange with regulatory sites in living cells.

Steroid receptors bind to site-specific response elements in chromatin and modulate gene expression in a hormone-dependent fashion. With the use of a tandem array of mouse mammary tumor virus reporter elements and a form of glucocorticoid receptor labeled with green fluorescent protein, targeting of the receptor to response elements in live mouse cells was observed. Photobleaching experiments provide direct evidence that the hormone-occupied receptor undergoes rapid exchange between chromatin and the nucleoplasmic compartment. Thus, the interaction of regulatory proteins with target sites in chromatin is a more dynamic process than previously believed.

Intranuclear trafficking and gene targeting by members of the steroid/nuclear receptor superfamily.

Upon binding to regulatory elements in mammalian chromosomes, steroid receptors induce specific transitions in the nucleoprotein structure of the template. These transitions reflect, in part, the reorganization of chromatin structure to permit interaction of secondary factors with target sequences in promoter regulatory regions. Steroid receptors represent a class of transcriptional activators that are able to interact with repressed nucleoprotein templates and recruit necessary activities for chromatin remodeling. The ligand-induced movement of nuclear receptors from inactive states, either in the cytoplasm or in the nucleus, to productive interactions with chromatin is complex and likely reflects the interaction with multiple protein complexes and subcellular structures. Regulation of gene expression by nuclear receptors is thus mediated through the subcellular distribution of inactive receptors, the redistribution of activated receptor complexes to appropriate nuclear domains, the reorganization of chromatin structures for interaction with soluble components of the nucleoplasm, and direct protein-protein contacts between receptors and the basal transcription apparatus.

Differential activity of progesterone and glucocorticoid receptors on mouse mammary tumor virus templates differing in chromatin structure.

In vivo, transcription factors interact with promoters having complex nucleoprotein structures. The transiently expressed progesterone receptor (PR) efficiently activates a transfected mouse mammary tumor virus (MMTV) promoter but is a poor activator of the MMTV promoter when it acquires an ordered chromatin structure as an endogenous, replicating gene. We show that the deficiency in PR activity is not due to insufficient expression of either B or A isoforms or competition between the two types of MMTV templates. Rather, this deficiency reflects an inability to induce the chromatin remodeling event that is required for activation of the replicated MMTV template. To determine whether this characteristic is common to transiently expressed steroid receptors or specific to the PR, we examined the activity of transiently expressed glucocorticoid (GR) receptor. Unlike the PR, the transiently expressed GR is an effective activator of both MMTV templates and efficiently induces the necessary chromatin remodeling event at the replicated template. These results indicate that the GR and PR have unique requirements for activation of promoters with ordered chromatin structure. These differences may provide a mechanism for establishing target gene specificity in vivo for steroid receptors that recognize and bind to identical DNA sequences.

Methemoglobinemia secondary to cleaning solution ingestion.

Methemoglobinemia is a rare cause of cyanosis in pediatric patients. A 16-month-old male presented to the Emergency Department cyanotic and short of breath after ingestion of a hair-care-equipment cleaning solution. After calling the salon and consulting Poisindex, the substance was found to be Mar-V-cide, containing 20% Hyamine 3500, 50% cationic detergents, 20% isopropyl alcohol, and 1% sodium nitrite, which caused the methemoglobinemia in this case. Initial pulse oximetry on room air was 72% and improved minimally with supplemented oxygen. The patient's methemoglobin level was 63%. Methylene blue was administered (2 mg/kg intravenously), and the patient rapidly improved. Nitrates occur in high concentrations in some food and water. Infants are particularly susceptible to chronic nitrate-induced methemoglobinemia because of their low stomach acid production, large numbers of nitrite-reducing bacteria, and the relatively easy oxidation of fetal hemoglobin. Acute nitrite toxicity results from industrial exposure, accidental ingestion (e.g., abuse of organic nitrites as an aphrodisiac, especially in the male homosexual population), and suicidal ingestion. Methemoglobinemia may occur in a number of drug or chemical ingestions, but a comprehensive review of the literature failed to identify a similar reported case.

Purification and stabilization of transcriptionally active glucocorticoid receptor.

A major obstacle to the purification of glucocorticoid receptor (GR) is the very high nonspecific surface adsorption of this protein. This phenomenon is a property of the GR itself and does not reflect overall protein concentration or buffer conditions. We have observed that the zwitterionic detergent 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonic acid (CHAPS) is unique in its ability to stabilize the receptor and largely eliminate loss to nonspecific adsorption. We have coupled this observation with a two-step purification method that allows efficient purification and stabilization of transcriptionally active glucocorticoid receptor. For this procedure, the GR first undergoes a major purification by anion exchange chromatography following hormone binding and on-column receptor transformation. Second, the GR is resolved to homogeneity utilizing a hydrophobic interaction chromatography step which consists of a 2.5 M to 0 M NaCl gradient elution of contaminating proteins followed by displacement of GR by CHAPS. GR at both stages of purification was able to activate transcription from the glucocorticoid response element containing the promoter region of the long terminal repeat of the mouse mammary tumor virus. This simple and efficient methodology should be of a considerable advantage for studies of the biology of the active, full-length GR.

Intervention research in construction: a hypothetical case study of painters.

This paper presents a theory on which to base intervention research in the construction industry, along with a hypothetical case study involving construction painters. The hypothetical case is based on data from research in a three-state study of construction painters currently under way. Difficulties facing researchers who conduct research in construction are described. Advantages of the intervention research design for construction are discussed.

Does the level of prehospital care influence the outcome of patients with altered levels of consciousness?

HYPOTHESIS: Significant differences exist in the outcome of patients with altered level of consciousness (ALOC) cared for by advanced life support (ALS) compared with basic life support (BLS) prehospital providers. METHODS: Patients transported by ambulance to a community teaching hospital during an 11-month period were studied retrospectively. Study patients were those considered not alert by prehospital personnel. Exclusion criteria included; trauma, intoxication, drowning, shock, and cardiac arrest. Data were abstracted from the ambulance reports and hospital records. RESULTS: Two hundred three patients with an ALOC were identified; 113 were transported by ALS providers (56%) and 90 (44%) by BLS providers. Prehospital levels of consciousness, according to the "alert, verbal, painful, unresponsive" scale (ALS vs BLS) were: "verbal" (40% vs 51%), "painful" (23% vs 23%), and "unresponsive" (37% vs 25%). The mean value for some time was 15 +/- 6 minutes for ALS versus 10 +/- 4 minutes for BLS (p < 0.001). On arrival in the emergency department, the LOC of 72 (64%) ALS patients and 58 (64%) BLS patients had improved to "alert." The level of consciousness in one ALS patient worsened. Fifty-two ALS (46%) and 38 (42%) BLS patients were admitted. Principal final diagnoses were seizure (27% ALS vs 38% BLS), hypoglycemia (23% ALS vs 23% BLS), and stroke (22% ALS vs 20% BLS). Remaining diagnoses each constituted less than 7% of total discharge diagnoses. No statistically significant differences in measures of outcome were noted between ALS or BLS patients. Diagnoses of seizure, stroke, and hypoglycemia were studied individually. No differences in admission rate, mortality rate, or disposition were identified. Hypoglycemic patients conveyed by ALS providers had significantly shorter emergency department treatment times than did those transported by BLS providers (160 +/- 62 minutes ALS vs 229 +/- 67 minutes BLS [p < 0.005]). CONCLUSION: Advanced life support levels of care of patients with an ALOC does not significantly change outcome compared with those receiving BLS care with the exception of shorter emergency department treatment times for hypoglycemic patients.

New processing strategies in cochlear implantation.

New strategies for representing acoustic information with multichannel cochlear implants have produced substantial improvements in speech recognition for implant users. This report reviews within-subject comparison of a new continuous interleaved sampling (CIS) strategy with a compressed analog (CA) strategy used in a standard clinical device. In general, the comparison show higher levels of open-set speech recognition with CIS for each of the 11 subjects studied. Data on the importance of the patients variable in determining outcomes with cochlear implants are presented. A brief description of another new strategy, the spectral maxima sound processor (SMSP) strategy is given as well as information on the availability of CIS in various implant systems.

Hearing preservation using the modified translabyrinthine approach.

Removal of an acoustic neuroma using the translabyrinthine approach has previously been considered "incompatible" with hearing preservation. By modifying the approach and preventing the loss of endolymph, we have successfully removed two intracanalicular acoustic neuromas that originated from the inferior vestibular nerves, and preserved serviceable hearing in the ears operated on. This report represents the preliminary findings using this particular technique in the management of intracanalicular acoustic neuromas.

Importance of patient and processor variables in determining outcomes with cochlear implants.

Within-subjects comparisons of processing strategies for cochlear implants are reviewed. Compressed analog strategies were compared to interleaved pulses strategies in tests with one group of 8 subjects, and to continuous interleaved sampling strategies in tests with another group of 11 subjects. The tests included open-set recognition of words and sentences. The results show that, while different strategies may produce quite different outcomes across subjects, individual performances with one processing strategy are significantly correlated with those of alternative strategies. These findings emphasize the importance of patient variables in determining outcomes across a variety of prosthesis designs.

Design and evaluation of a continuous interleaved sampling (CIS) processing strategy for multichannel cochlear implants.

Two approaches for representing speech information with multichannel cochlear prostheses are being compared in tests with implant patients. Included in these studies are the compressed analog (CA) approach of a standard clinical device and research processors utilizing continuous interleaved sampling (CIS). Initial studies have been completed with nine subjects, seven of whom were selected on the basis of excellent performance with the Ineraid clinical processor, and the remaining two for their relatively poor performance with the same device. The tests include open-set recognition of words and sentences. Every subject has obtained a higher score--or repeated a score of 100% correct--on every test when using a CIS processor. These results are discussed in terms of their implications for processor design.