Continued Development and Testing of a Novel Steerable Chest Tube, Extendable Infusion Cannula, and Portable Suction-Infusion Pump for Use in Austere and Transport Environments to Prevent Retained Hemothorax.

With blunt and penetrating trauma to the chest, warfighters frequently suffer from hemothorax. Optimal management requires the placement of a chest tube to evacuate the blood. Malposition of the tube may be a causative factor of inadequate drainage (retained hemothorax). As a potential solution, we developed a previously reported steerable chest tube allowing accurate placement into a desired location to enhance effectiveness. To provide assisted aspiration, we developed a portable, battery-operated suction device capable of simultaneous or sequential infusion. This report details the ongoing progress of this project. Updated steerable tube and pump prototypes were designed and produced. The tubes were tested for feasibility in two pigs and one cadaver by fluoroscopically comparing tip positions after insertion by a number of providers. Measured drainage volumes comparing standard vs. steerable tubes after pleural infusion of 1,000 mL of saline in two pigs were compared. Testing of the pump focused on the accuracy of suction and volume functions. The steerable tube prototype consists of sequentially bonded segments of differing flexibility and an ergonomic tensioning handle. The portable suction pump accurately provides up to 80 cmH2O of suction, an infusion capability of up to 10 mL/min, and a 950 mL removable reservoir canister. After minimal training, providers easily and repeatedly placed the tip of the steerable tube in the lateral diaphragmatic sulcus in animals and cadavers. Arc was limited to the distal segment. Compared to a standard tube, the steerable tube placed along the diaphragm improved pleural fluid drainage volumes by 17%, although this did not reach statistical significance in six trials. These new prototypes represent substantial improvements and were performed according to expectations. We believe that this steerable chest tube and portable suction-infusion pump can be effectively used for warfighters with chest injuries in austere environments.

Optimal Initial Positioning of Chest Tubes to Prevent Retained Hemothorax Using a Novel Steerable Chest Tube With Extendable Infusion Cannula.

INTRODUCTION: With blunt and penetrating trauma to the chest, warfighters and civilians frequently suffer from punctured lung (pneumothorax) and/or bleeding into the pleural space (hemothorax). Optimal management of this condition requires the rapid placement of a chest tube to evacuate as much of the blood and air as possible. Incomplete drainage of blood leading to retained hemothorax may be the result of the final tube tip position not being in contact with the blood collections. To address this problem, we sought to develop a "steerable" chest tube that could be accurately placed or repositioned into a specific desired position in the pleural space to assure optimal drainage. An integrated infusion cannula was added for the instillation of anticoagulants to maintain tube patency, thrombolytics for clot lysis, and analgesics for pain control if required. MATERIALS AND METHODS: A triple-lumen tube was designed to provide a channel for a pull-wire which was wound around an axle integrated into a small proximal handle and controlled by a ratcheted thumbwheel. Tension on the wire creates an arc on the tube that allows for positioning. In vitro testing focused on the relationship between the tension on the pull-wire and the resultant arc. Two adult cadavers and two anesthetized pigs were used to study the feasibility of accurate tube placement. After a brief training session, providers were asked to place tubes inferiorly along the diaphragm where blood was anticipated to accumulate or at the apex of the lung for pneumothorax. Success was determined with fluoroscopic images and was judged as a tube tip lying in the targeted position. RESULTS: The design was prototyped with an extruded polyvinyl chloride multilumen tube and a 3D printed tensioning handle. In vitro studies showed that one turn of the thumbwheel created 70° to 90° of arc of the tube. Cadaver and animal studies showed consistent success in the desired placement of the tube at or near the lateral diaphragm or in the apex. Attempts were also successful by surgical residents with minimal training. CONCLUSIONS: Initial preliminary studies on a novel steerable chest tube have demonstrated the ability to appropriately position the tube in a desired location. The addition of an extendable cannula will allow for safe clot lysis or maintained tube patency. Additional studies are planned to confirm the benefit of this device in preventing retained hemothorax.

Nontrauma surgeons can safely take call at an academic, rural level I trauma center.

BACKGROUND: Care protocols can facilitate effective management of injured patients across a spectrum of providers. It is uncertain whether patient care is compromised when a full time trauma surgeon is not on call in the rural setting, where manpower may be a challenge. METHODS: A retrospective cohort study was performed at an academic medical center with a level I trauma center. Patients admitted to the trauma service from 2007 to 2012 were compared with respect to mortality, missed injuries, delay in diagnosis, and length of stay based on whether they were admitted to the trauma service when a full-time trauma surgeon was on call. RESULTS: A total of 2,571 injured patients were admitted during the study period; 1,621 directly to the trauma service. Of those, 1,415 patients were initially seen by a trauma surgeon (group A) and 206 by a nontrauma surgeon (group B). Demographics were similar except that the trauma attending patients were somewhat older (44.7 vs 39.4 years, P = .002). There was no difference in the mean injury severity score (17.0 vs 16.0, P = .13) or Glasgow Coma Scale (12.7 vs 12.3, P = .7) between the 2 groups. There were 128 deaths; mortality rate in group A was 7.9% versus 7.7% for group B (P = .54). There was no difference in the incidence of delayed diagnosis or missed injuries (3.0 vs 3.4%, P = .8; .4 vs .9%, P = .27, respectively). The mean length of stay was shorter (7.9 vs 6.3, P = .016) in group B. CONCLUSIONS: There was no increase in mortality, delayed diagnosis, or missed injuries when nontrauma surgeons took call. Systems of care and algorithms can be developed that provide staffing flexibility yet maintain safe and effective care to trauma patients in the rural setting.

Langerhans cell histiocytosis in an adult with involvement of the calvarium, cerebral cortex and brainstem: discussion of pathophysiology and rationale for the use of intravenous immune globulin.

We report a case of Langerhans cell histiocytosis in a 64-year-old male who presented with symptoms and signs of brain involvement, including seizures and hypopituitarism. The diagnosis was confirmed with a biopsy of a lytic skull lesion. The disease affecting the bone showed no sign of progression following a short course of cladribine. Signs of temporal lobe involvement led to an additional biopsy, which showed signs of nonspecific neurodegeneration and which triggered status epilepticus. Lesions noted in the brainstem were typical for the paraneoplastic inflammation reported in this condition. These lesions improved after treatment with cladribine. They remained stable while on treatment with intravenous immune globulin.

A multitiered strategy of simulation training, kit consolidation, and electronic documentation is associated with a reduction in central line-associated bloodstream infections.

BACKGROUND: Simulation-based training has been associated with reduced central line-associated bloodstream infection (CLABSI) rates. We measured the combined effect of simulation training, electronic medical records (EMR)-based documentation, and standardized kits on CLABSI rates in our medical (MICU) and surgical (SICU) intensive care units (ICU). METHODS: CLABSI events and catheter-days were collected for 19 months prior to and 37 months following an intervention consisting of simulation training in central line insertion for all ICU residents, incorporation of standardized, all-inclusive catheter kits, and EMR-guided documentation. Supervising physicians in the MICU (but not the SICU) also completed training. RESULTS: Following the intervention, EMR-based documentation increased from 48% to 100%, and documented compliance with hand hygiene, barrier precautions, and chlorhexidine use increased from 65%-85% to 100%. CLABSI rate in the MICU dropped from 2.72 per 1,000 catheter-days over the 19 months preceding the intervention to 0.40 per 1,000 over the 37 months following intervention (P = .01) but did not change in the SICU (1.09 and 1.14 per 1,000 catheter-days, P = .86). This equated to 24 fewer than expected CLABSIs and $1,669,000 in estimated savings. CONCLUSION: Combined simulation training, standardized all-inclusive kits, and EMR-guided documentation were associated with greater documented compliance with sterile precautions and reduced CLABSI rate in our MICU. To achieve maximal benefit, refresher training of senior physicians supervising practice at the bedside may be needed.

Anticoagulation management around percutaneous bedside procedures: is adjustment required?

BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) and percutaneous dilatational tracheostomy (PDT) are frequently performed bedside in the intensive care unit. Critically ill patients frequently require anticoagulant (AC) and antiplatelet (AP) therapies for myriad indications. There are no societal guidelines proffering strategies to manage AC/AP therapies periprocedurally for bedside PEG or PDT. The aim of this study is to evaluate the management of AC/AP therapies around PEG/PDT, assess periprocedural bleeding complications, and identify risk factors associated with bleeding. METHODS: A retrospective, observational study of all adult patients admitted from October 2004 to December 2009 receiving a bedside PEG or PDT was conducted. Patients were identified by procedure codes via an in-hospital database. A medical record review was performed for each included patient. RESULTS: Four hundred fifteen patients were included, with 187 PEGs and 352 PDTs being performed. Prophylactic anticoagulation was held for approximately one dose before and two doses or less after the procedure. There was wide variation in patterns of holding therapy in patients receiving anticoagulation via continuous infusion. There were 19 recorded minor bleeding events, 1 (0.5%) with PEG and 18 (5.1%) with PDT, with no hemorrhagic events. No association was found between international normalized ratio, prothrombin time, or activated partial thromboplastin time values and bleed risk (p = 0.853, 0.689, and 0.440, respectively). Platelet count was significantly lower in patients with a bleeding event (p = 0.006). CONCLUSIONS: We found that while practice patterns were quite consistent in regard to the management of prophylactic anticoagulation, it varied widely in patients receiving therapeutic anticoagulation. It seems that prophylactic anticoagulation use did not affect bleed risk with PEG/PDT.

Transverse sinus thrombosis after internal jugular vein ligation.

BACKGROUND: Cerebral vein and dural sinus thrombosis is a rare condition with a wide range of causes and a highly variable presentation. It can lead to significant morbidity, but scant literature is available describing diagnosis and treatment when this occurs after ligation of the internal jugular vein. OBJECTIVES: To discuss potential risk factors for cerebral vein and dural sinus thrombosis after ligation of the internal jugular vein, and present current options for diagnosis and treatment. CASE REPORT: A 23-year-old male construction worker was brought to the Emergency Department by Emergency Medical Services after sustaining a severe neck laceration from a hand-held grinder. He was treated with ligation of the left internal jugular vein, but subsequently developed severe headaches and symptoms of increased intracranial pressure. A magnetic resonance venogram of the head revealed a left transverse sinus thrombosis requiring treatment with anticoagulation. The placement of a lumboperitoneal shunt was ultimately needed for relief of his symptoms. CONCLUSIONS: Early diagnosis and aggressive therapeutic interventions are critical to prevent further morbidity in patients who develop cerebral vein and dural sinus thrombosis after ligation of the internal jugular vein.

Swyer-James syndrome diagnosed in a trauma patient.

BACKGROUND: Swyer-James syndrome is a relatively rare pulmonary manifestation of prior childhood lung infection that results in hypoplastic lung with small-caliber bronchi and pulmonary vasculature. It appears as increased opacity on chest X-ray study and can be confused for other thoracic disease processes. CASE REPORT/OBJECTIVES: We present the confusing case of Swyer-James syndrome presenting in a trauma patient after a fall from 12 feet. The literature will be reviewed in regards to incidence, diagnosis, and management. CONCLUSIONS: Swyer-James syndrome occurs in < 0.01% of patients and is the result of usually recurrent childhood infections resulting in hypoplastic lung. It has classically been diagnosed with typical chest X-ray findings in the absence of obstructing lesions. More recently, diagnosis has been made by computed tomography. Management of the syndrome is typically conservative, with prevention and early treatment of pulmonary disease and, occasionally, resection for recalcitrant disease. In the presence of trauma, increased lung density on frontal chest X-ray study can be misconstrued as resulting from the trauma itself. This case outlines the need for emergency and trauma physicians to be cognizant of other etiologies of abnormal chest X-ray studies and to follow appropriate clinical pathways when working-up patients for chest trauma.

Functional residues on the surface of the N-terminal domain of yeast Pms1.

Saccharomyces cerevisiae MutLalpha is a heterodimer of Mlh1 and Pms1 that participates in DNA mismatch repair (MMR). Both proteins have weakly conserved C-terminal regions (CTDs), with the CTD of Pms1 harboring an essential endonuclease activity. These proteins also have conserved N-terminal domains (NTDs) that bind and hydrolyze ATP and bind to DNA. To better understand Pms1 functions and potential interactions with DNA and/or other proteins, we solved the 2.5A crystal structure of yeast Pms1 (yPms1) NTD. The structure is similar to the homologous NTDs of Escherichia coli MutL and human PMS2, including the site involved in ATP binding and hydrolysis. The structure reveals a number of conserved, positively charged surface residues that do not interact with other residues in the NTD and are therefore candidates for interactions with DNA, with the CTD and/or with other proteins. When these were replaced with glutamate, several replacements resulted in yeast strains with elevated mutation rates. Two replacements also resulted in NTDs with decreased DNA binding affinity in vitro, suggesting that these residues contribute to DNA binding that is important for mismatch repair. Elevated mutation rates also resulted from surface residue replacements that did not affect DNA binding, suggesting that these conserved residues serve other functions, possibly involving interactions with other MMR proteins.

5-ASA affects cell cycle progression in colorectal cells by reversibly activating a replication checkpoint.

BACKGROUND & AIMS: Individuals with inflammatory bowel disease are at risk of developing colorectal cancer (CRC). Epidemiologic, animal, and laboratory studies suggest that 5-amino-salicylic acid (5-ASA) protects from the development of CRC by altering cell cycle progression and by inducing apoptosis. Our previous results indicate that 5-ASA improves replication fidelity in colorectal cells, an effect that is active in reducing mutations. In this study, we hypothesized that 5-ASA restrains cell cycle progression by activating checkpoint pathways in colorectal cell lines, which would prevent tumor development and improve genomic stability. METHODS: CRC cells with different genetic backgrounds such as HT29, HCT116, HCT116(p53-/-), HCT116+chr3, and LoVo were treated with 5-ASA for 2-96 hours. Cell cycle progression, phosphorylation, and DNA binding of cell cycle checkpoint proteins were analyzed. RESULTS: We found that 5-ASA at concentrations between 10 and 40 mmol/L affects cell cycle progression by inducing cells to accumulate in the S phase. This effect was independent of the hMLH1, hMSH2, and p53 status because it was observed to a similar extent in all cell lines under investigation. Moreover, wash-out experiments demonstrated reversibility within 48 hours. Although p53 did not have a causative role, p53 Ser15 was strongly phosphorylated. Proteins involved in the ATM-and-Rad3-related kinase (ATR)-dependent S-phase checkpoint response (Chk1 and Rad17) were also phosphorylated but not ataxia telengectasia mutated kinase. CONCLUSIONS: Our data demonstrate that 5-ASA causes cells to reversibly accumulate in S phase and activate an ATR-dependent checkpoint. The activation of replication checkpoint may slow down DNA replication and improve DNA replication fidelity, which increases the maintenance of genomic stability and counteracts carcinogenesis.

Surgeon information transfer and communication: factors affecting quality and efficiency of inpatient care.

OBJECTIVE: To determine the nature of surgeon information transfer and communication (ITC) errors that lead to adverse events and near misses. To recommend strategies for minimizing or preventing these errors. SUMMARY BACKGROUND DATA: Surgical hospital practice is changing from a single provider to a team-based approach. This has put a premium on effective ITC. The Information Transfer and Communication Practices (ITCP) Project is a multi-institutional effort to: 1) better understand surgeon ITCP and their patient care consequences, 2) determine what has been done to improve ITCP in other professions, and 3) recommend ways to improve these practices among surgeons. METHODS: Separate, semi-structured focus group sessions were conducted with surgical residents (n = 59), general surgery attending physicians (n = 36), and surgical nurses (n = 42) at 5 medical centers. Case descriptions and general comments were classified by the nature of ITC lapses and their effects on patients and medical care. Information learned was combined with a review of ITC strategies in other professions to develop principles and guidelines for re-engineering surgeon ITCP. RESULTS: : A total of 328 case descriptions and general comments were obtained and classified. Incidents fell into 4 areas: blurred boundaries of responsibility (87 reports), decreased surgeon familiarity with patients (123 reports), diversion of surgeon attention (31 reports), and distorted or inhibited communication (67 reports). Results were subdivided into 30 contributing factors (eg, shift change, location change, number of providers). Consequences of ITC lapses included delays in patient care (77% of cases), wasted surgeon/staff time (48%), and serious adverse patient consequences (31%). Twelve principles and 5 institutional habit changes are recommended to guide ITCP re-engineering. CONCLUSIONS: Surgeon communication lapses are significant contributors to adverse patient consequences, and provider inefficiency. Re-engineering ITCP will require significant cultural changes.

RPA and PCNA suppress formation of large deletion errors by yeast DNA polymerase delta.

In fulfilling its biosynthetic roles in nuclear replication and in several types of repair, DNA polymerase delta (pol delta) is assisted by replication protein A (RPA), the single-stranded DNA-binding protein complex, and by the processivity clamp proliferating cell nuclear antigen (PCNA). Here we report the effects of these accessory proteins on the fidelity of DNA synthesis in vitro by yeast pol delta. We show that when RPA and PCNA are included in reactions containing pol delta, rates for single base errors are similar to those generated by pol delta alone, indicating that pol delta itself is by far the prime determinant of fidelity for single base errors. However, the rate of deleting multiple nucleotides between directly repeated sequences is reduced by approximately 10-fold in the presence of either RPA or PCNA, and by > or =90-fold when both proteins are present. We suggest that PCNA and RPA suppress large deletion errors by preventing the primer terminus at a repeat from fraying and/or from relocating and annealing to a downstream repeat. Strong suppression of deletions by PCNA and RPA suggests that they may contribute to the high replication fidelity needed to stably maintain eukaryotic genomes that contain abundant repetitive sequences.

Saccharomyces cerevisiae DNA polymerase delta: high fidelity for base substitutions but lower fidelity for single- and multi-base deletions.

Eukaryotic DNA polymerase delta (Pol delta) plays an essential role in replicating large nuclear genomes, a process that must be accurate to maintain stability over many generations. Based on kinetic studies of insertion of individual dNTPs opposite a template guanine, Pol delta is believed to have high selectivity for inserting correct nucleotides. This high selectivity, in conjunction with an intrinsic 3'-exonuclease activity, implies that Pol delta should have high base substitution fidelity. Here we demonstrate that the wild type Saccharomyces cerevisiae three-subunit Pol delta does indeed have high base substitution fidelity for the 12 possible base-base mismatches, producing on average less than 1.3 stable misincorporations/100,000 nucleotides polymerized. Measurements with exonuclease-deficient Pol delta confirm the high nucleotide selectivity of the polymerase and further indicate that proofreading enhances the base substitution fidelity of the wild type enzyme by at least 60-fold. However, Pol delta inefficiently proofreads single nucleotide deletion mismatches in homopolymeric runs, such that the error rate is 30 single nucleotide deletions/100,000 nucleotides polymerized. Moreover, wild type Pol delta frequently deletes larger numbers of nucleotides between distantly spaced direct repeats of three or more base pairs. Although wild type Pol delta and Pol epsilon both have high base substitution fidelity, Pol delta is much less accurate than Pol epsilon for deletions involving repetitive sequences. Thus, strand slippage during replication by wild type Pol delta may be a primary source of insertion and deletion mutagenesis in eukaryotic genomes.

The effects of group dynamics on resident progress committee deliberations.

BACKGROUND: Prior investigations suggest that resident progress decisions by committee provide a broader perspective on performance and result in less grade inflation. There is countervailing concern that group dynamics may compromise quality of progress decisions. PURPOSE: To determine whether and how group dynamics compromise decision making about resident progress. METHODS: Researchers recorded and analyzed participant comments during a resident progress committee meeting. End-of-rotation (EOR) evaluations were analyzed and compared to progress committee meeting results. RESULTS: EOR and progress committee comments were similar in content. The ratio of specific to general comments was higher for EOR evaluations (5:1) than for progress committee meetings (2:1). EOR evaluation comments provided more supporting evidence for assertions. Individual progress committee participants did not dominate discussion or sway decision making. Participant progress committee meeting comments were consistent with their EOR comments failing to support the presence of progress committee meeting "feeding frenzies." CONCLUSIONS: Results suggest that progress committee meeting group dynamics do not seriously compromise the validity of resident progress decisions.

Maximizing reimbursement from trauma response fees (UB-92: 68X) - lessons learned from a hospital comparison.

BACKGROUND: The trauma response fee (UB-92:68x) recently has been approved, to be used by hospitals to cover expenses resulting from continuous trauma team availability. These charges may be made by designated trauma centers for all defined trauma patients when notification has been received before arrival (eligible pt). This study compares two trauma centers' performance in collecting this fee help define methodologies that can enhance reimbursement. METHODS: Our trauma system uses two hospitals (A and B) that are designated as the Level I trauma center for the region on alternate years. This allows hospital performance comparisons with relatively consistent patient demographics, injury severity, and payer mix. Data were collected for a one-year period beginning on January 1, 2003 and included charges, collections, and payer source for the trauma response fee. This time frame allowed the comparison of two six-month sequential periods at each trauma center. RESULTS: Out of a total of 871 trauma patients, 625 were eligible for the trauma response fee (72%): hospital A = 65% and hospital B = 77%. Total trauma response fee charges for both centers were 1,111,882 dollars with collections of 319,684 dollars (28.8%). The following payer sources contributed to the collections: Indemnity insurance (77.4%), Managed Care (22.1%), Medicare (0.3%), and Medicaid (0.2%). No collections were obtained from any self-pay patient. Eligible patients were charged a trauma response fee much less frequently in Hospital A than B (29.35% versus 95.2%) but revenue / charge ratios were equivalent at both hospitals (0.32 versus 0.28). These differences resulted in markedly enhanced revenue for each eligible patient in Hospital B compared with A (735 dollars versus 174 dollars) CONCLUSIONS: Enhanced collection by hospital B was a result of a higher charge, compulsive billing of all eligible patients, and emphasis on pre-admission designation of trauma patients. Effective billing and collection process related to trauma response fees results in substantial additional revenue for the trauma center without additional expense.

Multihormonal regulation of hepatic sinusoidal Ntcp gene expression.

Bile acids are efficiently removed from sinusoidal blood by a number of transporters including the Na+-taurocholate-cotransporting polypeptide (Ntcp). Na+-dependent bile salt uptake, as well as Ntcp, are expressed twofold higher in male compared with female rat livers. Also, estrogen administration to male rats decreases Ntcp expression. The aims of this study were to determine the hormonal mechanism(s) responsible for this sexually dimorphic expression of Ntcp. We examined castrated and hypophysectomized rats of both sexes. Sex steroid hormones, growth hormone, thyroid, and glucocorticoids were administered, and livers were examined for changes in Ntcp messenger RNA (mRNA). Ntcp mRNA and protein content were selectively increased in males. Estradiol selectively decreased Ntcp expression in males, whereas ovariectomy increased Ntcp in females, confirming the importance of estrogens in regulating Ntcp. Hypophysectomy decreased Ntcp mRNA levels in males and prevented estrogen administration from decreasing Ntcp, indicating the importance of pituitary hormones. Although constant infusion of growth hormone to intact males reduced Ntcp, its replacement alone after hypophysectomy did not restore the sex differences. In contrast, thyroid hormone and corticosterone increased Ntcp mRNA in hypophysectomized rats. Sex differences in Ntcp mRNA levels were produced only when the female pattern of growth hormone was administered to animals also receiving thyroid and corticosterone. Thyroid and dexamethasone also increased Ntcp mRNA in isolated rat hepatocytes, whereas growth hormone decreased Ntcp. These findings demonstrate the essential role that pituitary hormones play in the sexually dimorphic control of Ntcp expression in adult rat liver and in the mediation of estrogen effects.

A senior elective designed to prepare medical students for surgical residency.

BACKGROUND: The transition from medical student to surgery internship can be stressful. The goal of this project was to design, implement, and evaluate a 1-month long elective course that would meet the majority of the American College of Surgeons Graduate Medical Education Committee prerequisites for graduate surgical education METHODS: The major elements of the curriculum included faculty- and resident-facilitated case-based sessions and cadaver dissections. In addition, the students participated in skills laboratory experiences, Intensive Care Unit rounds, and mock interviews and clinical pages. The students took a knowledge pretest and post-test that was compared with the performance of 8 surgical interns on the same examination. RESULTS: The highest rated elements of the course were those that provided hands-on experience or practical knowledge. The post-test knowledge examination scores were significantly higher than pretest scores and surgical intern scores. CONCLUSIONS: It was possible to develop a 1-month senior medical student elective course that provided students with the essential prerequisites believed to be essential for all surgical interns.

Effect of patient position on size and location of the subclavian vein for percutaneous puncture.

HYPOTHESIS: Large-bore subclavian intravenous access is important during trauma resuscitation and to provide central access in the intensive care unit. Controversy exists as to the patient position that best facilitates the insertion of this line. Duplex scanning of the subclavian vein in different body positions may help define which provides the largest vein size and distance from the clavicle. DESIGN: Prospective comparison study in healthy humans. SETTING: Clinical research laboratory. SUBJECTS: Ten healthy volunteers. INTERVENTIONS: We examined the left subclavian vein diameter, position from clavicle, and flow in subjects placed in 5 different positions advocated for subclavian vein puncture. A duplex scanner was used to image the subclavian vein with B-mode ultrasonography and to detect flow rates with a Doppler probe. The different subject positions were as follows: (1) flat (or supine), head and shoulders neutral; (2) flat, head neutral, shoulders arched; (3) flat, head opposite, shoulders arched; (4) Trendelenburg, head opposite, shoulders arched; and (5) Trendelenburg, head and shoulders neutral. RESULTS: The mean (SEM) diameter of the subclavian vein is largest in position 5 (0.99 [0.06] cm) and smallest in position 2 (0.84 [0.05] cm). The distance of the vein from the clavicle is greatest in position 1 (0.94 [0.08] cm) and least in position 4 (0.75 [0.07] cm). Using an analysis of variance with Dunnett's comparison, all positions were compared with position 5. For vein diameter, all positions had significantly smaller size. In position 4, the vein was significantly closer to the clavicle. There was no statistical difference in flow rates among all positions. CONCLUSIONS: These data demonstrate that arching of the shoulders and turning of the head may reduce target size and provide an unsatisfactory position for subclavian puncture. The Trendelenburg position with no other positioning maneuvers may be helpful.

DNA binding by yeast Mlh1 and Pms1: implications for DNA mismatch repair.

The yeast Mlh1-Pms1 heterodimer required for mismatch repair (MMR) binds to DNA. Here we map DNA binding to N-terminal fragments of Mlh1 and Pms1. We demonstrate that Mlh1 and Pms1 N-terminal domains (NTDs) independently bind to double-stranded and single-stranded DNA, in the absence of dimerization and with different affinities. Full-length Mlh1p alone, which can homodimerize, also binds to DNA. Substituting conserved positively charged amino acids in Mlh1 produces mutator phenotypes in a haploid yeast strain characteristic of reduced MMR. These substitutions strongly reduce DNA binding by the Mlh1 NTD and, to a lesser extent, they also reduce DNA binding by full-length Mlh1 and the Mlh1-Pms1 heterodimer. Replacement of a homologous Pms1 residue has a much smaller effect on mutation rate and does not reduce DNA binding. The results demonstrate that NTDs of yeast Mlh1 and Pms1 contain independent DNA binding sites and they suggest that the C-terminal region of Mlh1p may also contribute to DNA binding. The differential mutator effects and binding properties observed here further suggest that Mlh1 and Pms1 differ in their interactions with DNA. Finally, the results are consistent with the hypothesis that DNA binding by Mlh1 is important for MMR.

Stress ulcer prophylaxis in trauma patients.

INTRODUCTION: A number of issues concerning stress ulcer prophylaxis remain unresolved despite numerous randomized, controlled trials and several meta-analyses. The role of stress ulcer prophylaxis, particularly in trauma patients, is further complicated by the lack of trials utilizing clinically important bleeding as an endpoint. Given the lack of consensus regarding stress ulcer prophylaxis in trauma patients, prescribing practices at Level I trauma centers in the United States were assessed. MATERIALS AND METHODS: A survey was developed that contained questions related to institutional prescribing and evaluation of stress ulcer prophylaxis. The survey was intended to delineate these practices at the 188 Level I trauma centers (at the time of the present survey) in the United States. RESULTS: One hundred and nineteen surveys were returned, yielding a response rate of 63%. Eighty-six percent stated that medications for stress ulcer prophylaxis are used in a vast majority of trauma patients admitted to the intensive care unit. Sixty-five percent stated that there is one preferred medication. For these institutions, histamine-2-blockers were the most popular at 71%. Thirty-nine percent stated that greater than 50% of patients remain on stress ulcer prophylaxis following discharge from the intensive care unit. CONCLUSION: The lack of consensus with regards to appropriate stress ulcer prophylaxis is apparent in this survey of Level I trauma centers. For those institutions with a preferred agent, histamine-2-blockers were most common.