Evaluation of the patient with gastrointestinal bleeding: an evidence based approach.

Gastrointestinal bleeding is a common and potentially life-threatening problem. The incidence of upper gastrointestinal bleeding (UGIB) is 40 to 150 episodes per 100,000 population per year. Mortality in large series is 6% to 10% for UGIB and has remained unchanged over the past 30 to 60 years. The incidence of hospitalization for acute lower gastrointestinal bleeding is about 20 to 27 episodes per 100,000 population per year, with a 200-fold increase with advancing age from the third to ninth decades. The mortality rate is 4% to 10% or higher. The evaluation of overt or acute gastrointestinal bleeding in the ED is reviewed here from the perspective of evidence-based medicine.

Transcutaneous pacing in a hypothermic-dog model.

STUDY OBJECTIVE: To evaluate the hemodynamic response to transcutaneous pacing (TCP) during rewarming from hypothermia. METHODS: We conducted a prospective, controlled laboratory investigation using 20 mongrel dogs. The animals were anesthetized, intubated, and mechanically ventilated. Arterial pressure, core temperature, and cardiac rhythm were continuously monitored. All dogs were cooled to a core temperature of 27 degrees C; experimental animals were then subjected to TCP with active rewarming, and control animals underwent sham transcutaneous pacing and rewarmed in the same manner. Serial hemodynamic measurements, time to rewarming, and cardiac isoenzyme concentrations were analyzed. RESULTS: Rewarming was accomplished significantly faster in the paced group (171.5 +/- 31.5 minutes) than in the control group (254 +/- 55.9 minutes, P < .05). After rewarming, the mean cardiac index in the paced dogs returned to 84% of baseline, compared with 63% of baseline in the nonpaced group (P < .05). None of the paced animals demonstrated significant hemodynamic deterioration, potentially lethal arrhythmias, or other evidence of myocardial injury. CONCLUSION: TCP is safe, effective and easily implemented in dogs. In this small series of dogs, TCP restored and maintained hemodynamic stability and allowed the hypothermic animals to rewarm in half the time required by their nonpaced counterparts.

In vitro amoebicidal activity of propamidine and pentamidine isethionate against Acanthamoeba species and toxicity to corneal tissues.

Effective chemotherapy for Acanthamoeba keratitis has been hampered because of the marked resistance of the parasites to a variety of antimicrobial agents. In view of the fact that topical Brolene (propamidine isethionate) and neosporin are currently considered to be the medical treatment of choice in Europe, we sought to determine whether pentamidine may be equally effective, because the drug is more readily available to ophthalmologists in the United States. In this study, we compared the amoebicidal activity of the Brolene (commercial product), propamidine isethionate and pentamidine isethionate (Pentam) in vitro against three different species of Acanthamoeba, and the drugs' corresponding biocompatibility with rabbit corneal epithelial and endothelial cell cultures. The results indicated that there were significant species differences in drug sensitivity. Propamidine (> 1,000 micrograms/ml) was clearly less effective than pentamidine (> 125 micrograms/ml) against A. castellanii, although equivalent potency (> 250 micrograms/ml) was observed against A. polyphaga. On the other hand, propamidine (> 31.25 micrograms/ml) was slightly more effective than pentamidine (> 62.5 micrograms/ml) against A. hatchetti. Both drugs were also relatively nontoxic after short-term contact with cell cultures, even though the highest concentration of pentamidine caused low-grade injury to the superficial epithelium and reversible membrane damage to the endothelium. Steady-state levels of propamidine at effective amoebicidal concentrations, however, were much more toxic than pentamidine, which indicated that the drug has a much lower therapeutic index. Our data suggest that pentamidine may be an effective therapeutic option because of its potency and low toxicity.

Structure and practice of institutional review boards in the United States.

OBJECTIVE: The institutional review board (IRB) is a critical element in the protection of patients' and subjects' rights with regard to their participation in research protocols. The purpose of this study was to describe the structure and current practices of IRBs in the United States. METHODS: A self-administered questionnaire was mailed to the IRB chair of each U.S. hospital with a capacity of at least 400 beds (n = 907). The survey contained 21 questions outlining committee size and structure, review of research proposals, and policies concerning scientific misconduct. Chairs also were asked what advice they would offer a young investigator preparing a proposal for submission. RESULTS: A total of 488 surveys (54%) were returned; 447 of the responding institutions had an IRB committee. Committees had an average of 14 members, representing 27 medical specialties. Orthopedics had the least IRB representation (10% of committees), followed by emergency medicine (12%) and ophthalmology (15%). The majority of research proposals go through 5 specific steps once submitted for review. Common reasons for proposal rejection were improperly designed consent form (54%), poor study design (44%), unacceptable risk to subjects (34%), ethical or legal reasons (24%), and scientific merit (14%). When a research proposal is rejected, 86% of the responding IRBs assist the investigator in making appropriate revisions. Although a number of IRBs (17%) have dealt with scientific misconduct allegations, only 58% have a written policy regarding research integrity. CONCLUSION: Despite variations in committee structure and representation, IRBs have similar procedures for governing research. Investigators should be familiar with these procedures and are encouraged to discuss their proposal with an IRB representative prior to formal review.

Core temperature monitoring of firefighters during hazardous materials training sessions.

OBJECTIVE: To determine core temperature (Tc) elevations in hazardous materials (HazMat) technicians wearing level-A fully encapsulated, chemically resistive suits (FECRSs) during training scenarios. DESIGN: Cross-sectional, observational feasibility study with Institutional Review Board approval. SETTING: HazMat training scenarios held during the summer of 1994. Weather conditions included both rainy and sunny days, with a mean ambient temperature of 75.8 degrees F (24.3 degrees C) (range 69-83 degrees F [20.6-28.3 degrees C). PARTICIPANTS: Nine male firefighters participating in training scenarios in the Midwestern United States. INTERVENTIONS: Each volunteer swallowed a capsule containing a Tc sensor developed by the National Aeronautics and Space Administration. The capsule continuously monitored Tc and stored data in an ambulatory recorder worn under the level-A FECRS during training. RESULTS: Mean age of the volunteers was 34 years, mean weight was 92.6 kg, and average baseline Tc was 36.7 degrees C (97.1 degrees F) (range 35.3-38.2 degrees C [95.5-100 degrees F]). Time in the FECRS averaged 25.4 minutes (range 14-35 minutes). All subjects demonstrated increased Tc while in the suit; the mean Tc increase was 0.8 degree C (1.4 degrees F) (range 0.2-1.3 degrees C [0.4-2.3 degrees F]). The Tc continued to increase during wet decontamination procedures and after suit removal. Mean heat storage values (delta Tcx LBMx 3.47 kJ) were calculated, and found to be moderately elevated to 3.6 kJ/kg (range 2.1-4.6 kJ/kg). CONCLUSION: These observations support the validity and significance of implementing prophylactic measures for firefighters using protective clothing. Simple protective measures include enforced time limitations, hydration, and efforts to minimize heat buildup by avoiding both direct sunlight and unnecessary time encapsulated in the suit.

Part 2: using a competency-based curriculum to train experienced nurses in ventilator care.

As pediatric nurses, we are caring for increasing numbers of children with special health needs such as tracheostomy and ventilator care. These children are being discharged to their families requiring specialized care, including in-home skilled nursing services. In Part I of this two-part series, the authors described the development of a training curriculum for nurses caring for ventilator-assisted children at home. The next step was to validate that the curriculum was effective, feasible, and replicable. Part 2 describes the initial validation efforts with hospital and home care nurses.

In-field extremity amputation: prevalence and protocols in emergency medical services.

OBJECTIVE: To determine current experience, attitudes, and training concerning the performance of in-field extremity amputations in North America. DESIGN: Cross-sectional, epidemiological survey. PARTICIPANTS: Emergency medical services (EMS) directors from the 200 largest metropolitan areas in North America and attendees at the 1992 Mid-Year National Association of EMS Physicians Meeting. INTERVENTIONS: The survey consisted of five questions focusing on demographic and operational data, the frequency of occurrence of the performance of in-field amputations, personnel responsible for performing the procedure, existing written protocols for the procedure, and the scope of training provided. RESULTS: A total of 143 surveys was completed. Eighteen respondents (13%) reported a total of 26 in-field extremity amputations in the past five years. The most common cause for the injuries requiring amputations was motor-vehicle accidents. In the majority of cases (53.2%), trauma surgeons were responsible for performing the amputation, followed by emergency physicians (36.4%). Of respondents, 96% stated that there was no training available through their EMS agencies related to the performance of in-field extremity amputations. Only two EMS systems had an existing protocol regarding in-field amputations. CONCLUSIONS: The results suggest a need for established protocols to make the procedure easily accessible when needed, especially in large metropolitan EMS systems. This information should be emphasized during EMS training and reinforced through continuing education.

Developing a competency-based curriculum for tracheostomy and ventilator care.

Advances in technology and medical practice have enabled children with special health needs, such as tracheostomy and ventilator care, to be discharged to their families while continuing to require specialized care. Yet, corresponding increases in the availability and competence of home care providers have not kept pace with this trend. The authors set a goal to design, develop, implement, validate, and disseminate a competency-based curriculum to prepare adults to care for these children in the home and community. This article is Part 1 of a two-part series.

Chlorpromazine protection against Ca(2+)-dependent and oxidative cell injury. Limitations due to depressed mitochondrial function.

Chlorpromazine (CPZ), a phenothiazine, demonstrated both cytoprotective and toxic effects on cardiomyocytes. CPZ markedly reduced cytotoxicity caused by two toxic challenges, each with a distinct cytotoxic mechanism. Lethal cell injury was induced in cultured neonatal cardiomyocytes by either: (1) ionomycin, a Ca2+ ionophore that caused Ca(2+)-dependent cell injury; or (2) ethacrynic acid (EA), a glutathione (GSH) depletor that killed cells primarily via peroxidative damage. Pretreatment with 50 microM CPZ reduced the extent of ionomycin-induced cell death, as measured by lactate dehydrogenase (LDH) leakage, but enhanced the loss of intracellular ATP and collapsed the mitochondrial transmembrane potential (delta psi). In EA-treated cultures, 50 microM CPZ also lowered LDH leakage and diminished the peroxidative damage responsible for the cytotoxicity, but again enhanced the loss of intracellular ATP and collapsed the delta psi. CPZ protection was incomplete and limited to a narrow concentration range that was essentially identical for both toxic challenges. Maximum protection was observed with 50 microM CPZ, yet the amount of residual damage was similar to the degree of injury caused by a mitochondrial uncoupler, carbonylcyanide-m-chlorophenylhydrazone alone. In the absence of either challenge, 50 microM CPZ did not affect cellular energy status or kill the cells, but a higher concentration of CPZ (150 microM) did deenergize unchallenged cardiomyocytes. These data demonstrate that CPZ can reduce cytotoxicity caused by either Ca(2+)-dependent events or oxidative stress. However, even at an optimally protective level, CPZ in combination with either ionomycin or EA deenergized the cells, although neither toxic challenge nor 50 microM CPZ alone seriously affected delta psi. It would appear that intracellular perturbations induced by either challenge promote a depression of mitochondrial function by CPZ, which limits the protective action of the drug. Since both of the challenges used contain toxicologic features exhibited by a wide variety of toxic insults, results of this study have both mechanistic and clinical implications.

The role of tetracycline in chronic blepharitis. Inhibition of lipase production in staphylococci.

Tetracycline administered in low doses can be effective in the long-term management of patients with meibomian keratoconjunctivitis (MKC). However, the mechanism of action does not appear to be a reduction of bacteria. Seventy-five percent of the ocular staphylococci in such patients are resistant to tetracycline. An alternative mechanism of action could be the inhibition of production of extracellular enzymes by the ocular flora. Inhibition of lipase production could result in lowered levels of toxic hydrolysis products (free fatty acids), which may exacerbate the disease process. The authors tested this hypothesis by examining the differential effect of tetracycline on growth and lipase production in a tetracycline-resistant and tetracycline-sensitive strain of Staphylococcus epidermidis and S. aureus isolated from patients with MKC and Staphylococcal blepharitis. Tetracycline caused significant decreases in the production of lipase in the sensitive and resistant strains of S. epidermidis without concominant decreases in growth. In contrast, S. aureus strains showed parallel decreases in both lipase production and inhibition of growth. The authors propose that the sensitivity of lipase production to tetracycline, in tetracycline-resistant S. epidermidis, may partially explain the clinical improvement observed in MKC patients.

In vitro penetration of human corneal epithelium by Acanthamoeba castellanii: a scanning and transmission electron microscopy study.

Human corneal buttons were exposed to Acanthamoeba castellanii trophozoites and cysts for 12 hours at 35 degrees C. The buttons examined by light microscopy and scanning and transmission electron microscopy had severe epithelial ulceration and penetration by trophozoites. Observations on trophozoites below the surface suggest that penetration is accomplished by both secreted cytolytic enzymes and phagocytosis. It is likely that the secretion of one or more enzymes constitutes the initial step in preparing the host tissue for endocytosis or that the secretory mechanism is used by the amebas to move through the outer squamous layer to the basement epithelium where phagocytosis occurs. Based on this study and a previous study, it appears that entry into the cornea is a two-step process involving adherence and penetration by trophozoites.

In vitro intercellular adherence of Acanthamoeba castellanii: a scanning and transmission electron microscopy study.

Human corneal buttons were exposed to trophozoites and cysts of Acanthamoeba castellanii for 12 hours. Examination of the buttons by scanning electron microscopy showed numerous trophozoites on the surface of the epithelium. Trophozoites examined by transmission electron microscopy had limited regions of attachment to the epithelium but extensive regions of attachment to each other. Attachment regions were characterized as plaque-like maculae of an incomplete desmosome junction. Firm attachment mechanisms may explain how penetration of the human cornea occurs.

Effect of contact lens preservatives on Acanthamoeba.

Single preservatives used in contact lens solutions were evaluated for their effectiveness in killing Acanthamoeba castellanii and Acanthamoeba polyphaga trophozoites and cysts. Preservatives were tested against amoebae at intervals varying from 30 minutes to 24 hours. The preservatives were tested with axenically and nonaxenically grown organisms. Chlorhexidine (0.001% and 0.005%), polyaminopropyl biguanide (0.0015%), benzalkonium chloride (0.001% and 0.004%), and hydrogen peroxide (3%) were very effective preservatives. Lower concentrations of these same preservatives were less effective. Thimerosal (0.001% and 0.004%), sorbic acid (0.1%), potassium sorbate (0.13%), EDTA (0.1%), polyaminopropyl biguanide (0.00005%), and polyquaternium-1 (0.001%) were not effective as tested. However, thimerosal 0.004% when combined in solution with EDTA was effective. Preservatives were more effective when tested against axenically prepared organisms than when tested against co-cultured organisms.

The role of wax and sterol ester fatty acids in chronic blepharitis.

The authors analyzed the long-chain fatty acids derived from the wax and sterol ester fractions of meibomian secretions from patients with chronic blepharitis and normal individuals. Meibomian secretions were partitioned into separate lipid classes by thin-layer chromatography (TLC). Wax and sterol esters were eluted and transesterified. The liberated fatty acid methyl esters (FAME) were analyzed by gas liquid chromatography. Equivalent chain lengths (ECL) were determined for the 58 peaks found. Thirty-three peaks were positively identified by standards. Peaks were quantified by area normalization. Percentage compositions were computed for each individual and tabulated by group; each fatty acid was analyzed by analysis of variance, and each clinical group was compared with normal subjects. The authors found increases in the series of monounsaturated fatty acids from patient wax/sterol esters compared with normal subjects (P less than 0.05). The authors also found differences in some members of the series of normal, straight, and branched saturated moieties. These differences between normal groups and the blepharitic groups represent a biologically significant pattern that may relate to the disease process. Discriminant analysis provided a 73% probability of correct classification into clinical groups based strictly on FAME analysis (P less than 0.05).

Ilionguinal-iliohypogastric nerve entrapment.

Ilionguinal-iliohypogastric nerve entrapment was described as early as 1942 as a rare but proven cause of chronic inguinal pain in patients with previous lower abdominal surgery. We describe two cases of patients who presented to the emergency care unit with complaints of chronic lower abdominal pain. Surgical histories revealed known risk factors for ilioinguinal-iliohypogastric nerve entrapment. After application of a simple bedside procedure, the diagnoses were confirmed.

Negative pressure devices in pediatric practice.

Pediatric nurses are seeing a renewed interest in the use of negative pressure ventilators in the hospital and home setting. Although body ventilators are a novelty to many nurses, they also present several challenges for safe and supportive care.

The effect of currently available contact lens disinfection systems on Acanthamoeba castellanii and Acanthamoeba polyphaga.

Contact lens disinfection systems were evaluated for their effectiveness in killing Acanthamoeba castellanii and Acanthamoeba polyphaga trophozoites and cysts. Amoebae were inoculated into commercially available contact lens cleaning and soaking solutions. At intervals varying from 30 minutes to 24 hours, solutions were filtered. The filters were removed and cultured for Acanthamoeba organisms. Striking differences were observed in the abilities of the different disinfecting solutions to kill the organisms. Solutions containing chlorhexidine were effective at very short exposure times. Solutions containing benzalkonium chloride required slightly longer exposure times but were faster than solutions containing only thimerosal. Solutions containing sorbate, polyaminopropyl biguanide, or polyquaternium-1 were not effective at killing Acanthamoeba organisms in the time allotted for the experiment. Solutions containing hydrogen peroxide were quite effective if the agent was not prematurely catalyzed. A. polyphaga generally required longer exposure to disinfectants than did A. castellanii for complete inhibition to occur.

Hyperacute T-wave criteria using computer ECG analysis.

Hyperacute T waves (HATWs) have been described as tall-amplitude, primary T-wave abnormalities sometimes seen in the early phases of transmural myocardial infarction. Despite numerous human and animal studies addressing the presence and significance of HATWs, there are no widely held, reliable ECG criteria for their accurate identification. Using a specially designed computer program on a Hewlett-Packard Realm ECG analysis system, we screened 13,393 adult ECGs to identify those having T-wave amplitudes greater than accepted standards (limb leads, greater than 0.5 mV; precordial leads, greater than 1.0 mV). Patients with other known causes of primary and secondary tall T waves were excluded from the study sample. Patients with tall-amplitude T-waves who then developed clinically verifiable myocardial infarction were labeled the HATW group. The HATW group (21) represented 4.1% of the tall T wave group (513) and 0.16% of the entire sample. The remaining patients, who did not meet HATW criteria, were called the early repolarization variant (ERV) group (51). Both groups underwent comparative computer morphology analysis. Nine parameters were statistically significant in discriminating HATWs from early repolarization variants. A combination of J-point position/T-wave amplitude of more than 25%, T-wave amplitude/QRS amplitude of more than 75%, J-point position of more than 0.30 mV, and age of more than 45 years predicted HATWs from a control group with a specificity of 98.0% and a sensitivity of 61.9% and with positive and negative predictive values of 92.9% and 86.2%, respectively. We conclude that HATWs have characterizable discriminating ECG morphology as determined by computer ECG analysis compared with a control group.

The role of wax and sterol esters of meibomian secretions in chronic blepharitis.

We analyzed the fatty wax esters and sterol esters found in the expressed lipid secretions of six patients from each of six clinical groups of chronic blepharitis, plus eight normal controls. Using gas liquid chromatography (GLC), 12 peaks corresponding to equivalent chain lengths (ECL) of 33.6, 35.4, 36.1, 37.3, 38.2, 39.2, 40.1, 41.2, 42.1, 43.2, 44.9 and 45.7 were found in the fatty wax esters and five peaks corresponding to ECL 19.1, 20.0, 21.1, 22.0 and 23.2 were found in the sterol esters. The clinical groups showed significant differences in several of these components. Sterol and wax esters represent the largest fraction of the total meibomian lipid secretion. The finding that the blepharitic groups exhibit biochemical differences in the distribution of these esters indicates that the esters may play a role in the disease process, perhaps by providing a preferential substrate for normal flora which we have shown to have lipolytic capabilities. The resultant de-esterification could alter the tear film and contribute to ocular irritation. In addition, the differences seen in the composition of the ester fraction of the meibomian secretion could lead to differences in melting point, which, in turn, could affect viscosity and surface tension of the tear film, leading to changes in breakup time and to secretion stagnation within glands.