Control of Pelvic Blood Flow Using a Novel Pneumatic Abdominal Binder.

Background Obstetrical hemorrhage continues to be the leading cause of maternal death; additional means of treatment are needed to reach women who are currently not being saved. We developed the "Ball and Binder", an inexpensive and innovative pneumatic abdominal-pelvic compression device made with a cloth binder and soccer ball. Objective To measure the change in distal aortic blood flow before and after placement of the device. Method A comparative study was done on nine healthy volunteers measuring the flow in the distal aorta before and after placement of a pneumatic abdominal binder. Result Distal aortic flow decreased by over half when the device was inflated. Conclusion An inexpensive pneumatic external abdominal compression "Ball and Binder" device was able to decrease flow to the pelvis by over half. This provides an additional tool for rapid treatment of postpartum hemorrhage unresponsive to routine initial measures.

Discovery and optimization of 2-aryl oxazolo-pyrimidines as adenosine kinase inhibitors using liquid phase parallel synthesis.

Adenosine kinase inhibition is an attractive therapeutic approach for several conditions for example, neurodegeneration, seizures, ischemia, inflammation and pain. Several nucleosidic and non-nucleosidic inhibitors are available. Using a virtual screening approach, we have discovered that 2-aryl oxazolo-pyrimidines are adenosine kinase inhibitors. Subsequent high throughput derivatization enabled the optimization of this new inhibitor chemotype resulting in highly potent derivatives. A variety of analogues were produced by applying liquid phase parallel synthesis to vary the 7-amino residues as well as the 2-aryl moiety.

Maximizing comfort and minimizing ischemia: a comparison of four methods of spinal immobilization.

OBJECTIVE: To determine which of four methods of spinal immobilization causes the least ischemic pain. METHODS: A prospective, nonblinded comparative trial was conducted at a statewide emergency medical services training facility using a convenience sample of emergency medical technician students. After lying motionless for 10 minutes, students evaluated each device using a 10-centimeter visual analog scale. Subjective comfort was used as a measure of ischemia. RESULTS: Comfort scores were significantly different for all methods (F = 101, p < 0.001). A backboard padded with a gurney mattress and eggcrate foam (the equivalent of a spinal rehabilitation bed) caused the least ischemic pain (9.6 cm, 95% CI, 8.9 to 9.8 cm). A backboard padded with a gurney mattress was the second most comfortable device (7.0 cm, 95%/CI, 6.4 to 7.4 cm). A backboard padded with a folded blanket was the third most comfortable (3.3 cm, 95% CI, 2.6 to 4.9 cm). The backboard alone caused the most pain (0.8 cm, 95% CI, 0.7 to 2.1 cm). CONCLUSION: Increasing the amount of padding on a backboard decreased the amount of ischemic pain caused by immobilization.

Structural alignment of ferredoxin and flavodoxin based on electrostatic potentials: implications for their interactions with photosystem I and ferredoxin-NADP reductase.

The two proteins ferredoxin and flavodoxin can replace each other in the photosynthetic electron transfer chain of cyanobacteria and algae. However, structure, size, and composition of ferredoxin and flavodoxin are completely different. Ferredoxin is a small iron-sulfur protein (approximately 100 amino acids), whereas flavodoxin is a flavin-containing protein (approximately 170 amino acids). The crystal structure of both proteins from the cyanobacteria Anabeana PCC 7120 is known. We used these two protein structures to investigate the structural basis of their functional equivalence. We apply the Hodgkin index to quantify the similarity of their electrostatic potentials. The technique has been applied successfully in indirect drug design for the alignment of small molecule and bioisosterism elucidation. It requires no predefined atom-atom correspondences. As is known from experiments, electrostatic interactions are most important for the association of ferredoxin and flavodoxin with their reaction partners photosystem I and ferredoxin-NADP reductase. Therefore, use of electrostatic potentials for the structural alignment is well justified. Our extensive search of the alignment space reveals two alignments with a high degree of similarity in the electrostatic potential. In both alignments, ferredoxin overlaps completely with flavodoxin. The active sites of ferredoxin and flavodoxin rather than their centers of mass coincide in both alignments. This is in agreement with electron microscopy investigations on photosystem I cross-linked to ferredoxin or flavodoxin. We identify residues that may have the same function in both proteins and relate our results to previous experimental data.

Confusing extrication with immobilization: the inappropriate use of hard spine boards for interhospital transfers.

INTRODUCTION: To determine if air medical interhospital transport of patients with spinal injuries is done with techniques that minimize ischemic skin damage. METHODS: A formal telephone survey instrument was given to all U.S. flight services accredited by the Commission on Accreditation of Medical Transport Systems (CAMTS). RESULTS: Thirty-seven active services were listed by CAMTS; the author's service was excluded from the survey. One service did only scene responses; one was unreachable by phone; four were unwilling to complete the form, leaving 30 services for evaluation. Twenty-nine services used metal, plywood, or plastic "spine" boards for immobilization during interhospital transport. Eight services padded boards with blankets or cloth for patients immobilized for "extended periods." Eighteen services routinely reimmobilized all major trauma patients even if cleared by the sending physician, and four others reimmobilized patients not "cleared" by a radiologist. No service moved patients with known spinal injuries to softer, more conforming devices before transport. Only three services followed patients for complications throughout hospitalization. Two services reported cases of skin breakdown thought to be a result of prolonged immobilization. CONCLUSION: Air medical services often transport patients several hours after injury. Patients, particularly those unable to move because of their injuries, medication, or paralysis, are at risk for ischemic necroses of their skin. Decubitus ulcers are a major cause of morbidity and mortality, and preventing ulcers requires a very soft, conforming surface. Despite these facts, the highly select services surveyed continue to use hard, slippery boards designed for extrication at trauma scenes to immobilize patients for transport.

A new approach to teaching prehospital trauma care to paramedic students.

STUDY OBJECTIVE: A modification of the standard Department of Transportation student paramedic curriculum encouraging individualized patient assessment decreases inappropriate on-scene procedures (OSPs) and scene time, measured on simulated patients. METHODS: Scenario-based testing from 1991 through 1993 was videotaped for all students. A new trauma curriculum was introduced in 1992, individualizing patient assessment and prioritization of OSPs. Recorded OSPs included spinal immobilization, application of military antishock trousers, endotracheal intubation, cricothyrotomy, intravenous catheter insertion, and needle thoracostomy. Twenty videotaped random student performances of the 1991 class was compared with a similar sample of 20 from the 1993 class; scene times and the OSP numbers were measured. Two board-certified independent emergency physicians unfamiliar with the students or the new curriculum reviewed all 40 tests on a master videotape. Patient assessment appropriateness, scene time, OSPs, scenario difficulty, and number of inappropriate OSPs were evaluated using a linear analog scale. Data are presented as means with confidence intervals (CIs), analyzed by Student's t test and the Mann-Whitney 2-sample test. RESULTS: Scene time from 1991 to 1993 decreased overall with a mean of 4.3 minutes (95% CI 2.8 to 5.8 minutes), as did the number of OSPs: 3.1 versus 1.7 (mean difference, 1.45 OSPs per scenario; 95% CI.91 to 1.99). Physician reviewers noted improvements in the appropriateness of patient assessment, scene time, and OSPs from 1991 to 1993. There was no significant difference in scenario difficulty for 1991 compared with 1993. Inappropriate OSPs done on scene declined. Physician 1 indicated a mean of inappropriate procedures of 1.6 in 1991 versus.5 in 1993. Physician 2 indicated a mean of 1.4 in 1991 versus.3 in 1993. CONCLUSION: This new paramedic curriculum decreased on-scene time and inappropriate use of procedures in stabilizing the condition of patients with simulated critical trauma.

Out-of-hospital spinal immobilization: its effect on neurologic injury.

OBJECTIVE: To examine the effect of emergency immobilization on neurologic outcome of patients who have blunt traumatic spinal injuries. METHODS: A 5-year retrospective chart review was carried out at 2 university hospitals. All patients with acute blunt traumatic spinal or spinal cord injuries transported directly from the injury site to the hospital were entered. None of the 120 patients seen at the University of Malaya had spinal immobilization during transport, whereas all 334 patients seen at the University of New Mexico did. The 2 hospitals were comparable in physician training and clinical resources. Neurologic injuries were assigned to 2 categories, disabling or not disabling, by 2 physicians acting independently and blinded to the hospital of origin. Data were analyzed using multivariate logistic regression, with hospital location, patient age, gender, anatomic level of injury, and injury mechanism serving as explanatory variables. RESULTS: There was less neurologic disability in the unimmobilized Malaysian patients (OR 2.03; 95% CI 1.03-3.99; p = 0.04). This corresponds to a <2% chance that immobilization has any beneficial effect. Results were similar when the analysis was limited to patients with cervical injuries (OR 1.52; 95% CI 0.64-3.62; p = 0.34). CONCLUSION: Out-of-hospital immobilization has little or no effect on neurologic outcome in patients with blunt spinal injuries.

Seat belt use in a developing country: covert noncompliance with a primary enforcement law in Malaysia.

Malaysia has strict laws requiring seat belt use by all vehicle occupants. However, neither passive devices nor inertial reel belts are mandated. Seat belt usage was investigated among 60 taxicab drivers in Kuala Lumpur, Malaysia, in 1993. Although all drivers appeared to be restrained during an initial curb-side inspection, 60% did not fasten the latch. There was no statistical difference between ethnic groups. Curb-side estimates of restraint use may overestimate actual usage, resulting in falsely low estimates of effectiveness. Requiring inertial reel belts, which would retract if not latched, could greatly increase actual restraint use. This may be cost effective for developing nations.

Designing a prehospital system for a developing country: estimated cost and benefits.

Many of the costs associated with prehospital care in developed countries are covered in budgets for fire suppression, police services, and the like. Determining these costs is therefore difficult. The costs and benefits of developing a prehospital care system for Kuala Lumpur, Malaysia, which now has essentially no emergency medical services (EMS) system, were estimated. Prehospital therapies that have been suggested to decrease mortality were identified. A minimal prehospital system was designed to deliver these treatments in Kuala Lumpur. The potential benefit of these therapies was calculated by using statistics from the United States corrected for demographic differences between the United States and Malaysia. Costs were extrapolated from the current operating budget of the Malaysian Red Crescent Society. Primary dysrhythmias are responsible for almost all potentially survivable cardiac arrests. A system designed to deliver a defibrillator to 85% of arrests within 6 minutes would require an estimated 48 ambulances. Kuala Lumpur has approximately 120 prehospital arrhythmic deaths per year. A 6% resuscitation rate was chosen for the denominator, resulting in seven survivors. Half of these would be expected to have significant neurological damage. Ambulances cost $53,000 (US dollars) to operate per year in Kuala Lumpur; 48 ambulances would cost a total of $2.5 million. Demographic factors and traffic problems would significantly increase the cost per patient. Other therapies, including medications, airway management, and trauma care, were discounted because both their additional cost and their benefit are small. Transport of patients (including trauma) is now performed by police or private vehicle and would probably take longer by ambulance. A prehospital system for Kuala Lumpur would cost approximately $2.5 million per year. It might save seven lives, three of which would be marred by significant neurological injury. Developing countries would do well to consider alternatives to a North American EMS model.

Prescribing analgesics: the effect of patient age and physician specialty.

To determine if patient age or physician specialty influences the willingness to prescribe pain medication, a mail survey was made of all emergency physicians, family practice physicians, and pediatricians listed as practicing in a single, middle sized, urban county in the southwest. The survey instrument presented a typical case of otitis media complicated only by pain so severe that the patient had been unable to sleep. Physicians were asked specifically if they would prescribe an analgesic and if so what kind. Emergency and family practice physicians were presented on a random basis with cases that were identical except the age was given at two or 22 years old. Pediatricians were given only the two year old. Eighty percent (137/165) of the surveys were completed and returned. Only 28% of the physicians would prescribe medications stronger than acetaminophen or nonsteroidal antiinflammatory drugs. There was a trend toward more narcotic analgesics for the 22 year old (41 vs 22% Fisher's exact test P = 0.03). Emergency physicians were the most generous, prescribing narcotics (codeine or oxycodone compounds) half the time (50%) versus one quarter of the time (22%) for family practice physicians and pediatricians (Fisher's exact test, P < 0.01). Pediatricians and family practice physicians did not differ (20 vs. 25%, P = 0.8). Potent analgesics are rarely prescribed by our sample physicians. Children are somewhat less likely to receive narcotics than adults with the same complaint. Emergency physicians are more likely to prescribe potent analgesics than are family practice physicians or pediatricians.

Comparison of the physiologically equivalent proteins cytochrome c6 and plastocyanin on the basis of their electrostatic potentials. Tryptophan 63 in cytochrome c6 may be isofunctional with tyrosine 83 in plastocyanin.

The blue copper protein plastocyanin and the heme protein cytochrome c6 differ in composition and in structure but perform the same function in the photosynthetic electron-transport chain. We compare these two proteins on the basis of their electrostatic potentials in order to understand the structural basis of their functional equivalence. In the first approach, we use a monopole-dipole approximation of the electrostatic potentials to superimpose the proteins. The resulting alignment suggests that Tyr51 in cytochrome c6 corresponds to Tyr83 in plastocyanin. But since Tyr51 is not conserved in all known cytochrome c6 sequences, a physiological role of this residue is questionable. In a more sophisticated approach, we applied the recently-developed Fame (flexible alignment of molecule ensembles) algorithm, in which molecules are superimposed by optimizing the similarity of their electrostatic potentials with respect to the relative orientation of the molecules. On the basis of the Fame alignments of plastocyanin and cytochrome c6, we analyze the docking and the electron-transfer reactions of these two proteins with its physiological reaction partner cytochrome f. We derive functional analogies for individual amino acids in possible electron-transfer paths in the interprotein redox reactions. We identify two surface patches in cytochrome c6 that may be involved in electron-transfer paths. The hydrophobic patch with the exposed heme edge in cytochrome c6 may be equivalent to the hydrophobic patch with His87 in plastocyanin, whereas Trp63 in cytochrome c6 may be equivalent to Tyr83 in plastocyanin. An aromatic amino acid is present at the position of Trp63 in all known cytochrome c6 sequences. The electronic coupling between the heme and the copper site on the one side and several potentially important amino acid residues on the other is analyzed by the Pathways method. We have proposed recently that Lys65 of cytochrome f and Tyr83 of plastocyanin form a cation-pi system, which may be involved in a two-step mechanism of the electron-transfer reaction between these two proteins from higher plants. Now we corroborate this proposal by analyzing available amino acid sequences.

Comparison of a vacuum splint device to a rigid backboard for spinal immobilization.

In this study, comparison of a vacuum splint device to a rigid backboard was made with respect to comfort, speed of application, and degree of immobilization. The study was a prospective, nonblinded comparative study conducted at a statewide emergency medical services (EMS) training facility and included a convenience sample of emergency medical technician (EMT) and paramedic students. The vacuum splint was judged to be significantly more comfortable on a 10-point scale than the rigid backboard after subjects had been lying on each device for 30 minutes (P < .001). It was also faster to apply: 131.6 +/- 24.3 seconds versus 154.6 +/- 22.2 seconds (P < .001). Various measures of immobilization were similar for the two devices. The vacuum splint provided better Immobilization of the torso and less slippage on a gradual lateral tilt. The rigid backboard with head blocks was slightly better at immobilizing the head. Vacuum splints offer a significant improvement in comfort over a traditional backboard for the patient with possible spinal injury. They can be applied in reasonable time frames and provide a similar degree of immobilization when compared to a standard rigid backboard.

Use of the endotracheal tube as a pharyngeal airway.

An animal study was conducted to determine whether an endotracheal tube placed above the vocal cords in the pharynx can be used for ventilation. Four dogs undergoing general anesthesia were ventilated through an endotracheal tube placed in the oropharynx with the remainder of the airway occluded. Ventilation was performed for 3 of every 5 minutes during a total period of 25 minutes. Arterial PCO2 was compared in sequential samples alternating apnea and pharyngeal ventilation. Ventilation via the pharyngeal tube significantly reduced the arterial PCO2 from 48.8 mm Hg (SD 16) during apnea to 30.1 mm Hg (SD 10.9). Repeated measures ANOVAF = 8.2, P < .001. All PCO2 levels during ventilation were in or below the normal range of 34 to 46. Provided that the mouth and nose can be sealed, an endotracheal tube placed in the pharynx above the cords allows for adequate ventilation.

Percutaneous needle cricothyroidotomy with repetitive airway obstruction.

To develop a technique for needle cricothyrotomy that mimics the normal respiratory cycle (using repetitive obstruction of the upper airway and relatively low flow oxygen through small catheters), a controlled trial in three anesthetized dogs was performed. Oxygen from a standard bottle and pressure reducer was delivered through the cricothyroid membrane at 0.36 L/kg/min, which is metabolically equivalent to 0.2 L/kg/min in an adult human. The upper airway was obstructed until the chest rose and then was unobstructed to allow exhalation. The animals were ventilated for 5 minutes to allow equilibration. Arterial PCO2 was measured after 2-minute periods of apnea and 3 minutes of ventilation, each repeated four times. The procedure was repeated in three other dogs at a flow of 0.18 L/kg/min to simulate a 50% air leak. Cricothyroid ventilation at 0.36 L/kg/min lowered the PCO2 from 65 mm Hg to 43 mm Hg, F = 258, P = .004. All PCO2 after 25 minutes were in the normal range. Ventilation at 0.18 L/kg/min stabilized the PCO2 at approximately 1.5 times normal (67 mm Hg versus 79 mm Hg for the preceding apnea, F = 77, P = .013). Flow rates achievable with 18- to 20-gauge catheters and standard oxygen sources are adequate for cricothyroid ventilation when the airway is repetitively obstructed to allow a normal respiratory cycle.