A potentially expanded role for enoxaparin in preventing venous thromboembolism in high risk blunt trauma patients.

BACKGROUND: Venous thromboembolism (VTE) is a frequent and potentially life-threatening complication after trauma. The purpose of this study is to investigate the effectiveness of enoxaparin in preventing deep venous thrombosis (DVT) and pulmonary embolism (PE) after injury in patients who are at high risk for developing VTE. STUDY DESIGN: A prospective single-cohort observational study was initiated for seriously injured blunt trauma patients admitted to a Level I trauma center during a 7-month period. Patients were eligible for the study if time hospitalized was > or = 72 hours, Injury Severity Score (ISS) was > or = 9, enoxaparin was started within 24 hours after admission, and one or more of the following high risk criteria were met: age > 50 years, ISS > or = 16, presence of a femoral vein catheter, Abbreviated Injury Score (AIS) > or = 3 for any body region, Glasgow Coma Scale (GCS) Score < or = 8, presence of major pelvic, femur, or tibia fracture, and presence of direct blunt mechanism venous injury. Patients with closed head injuries and nonoperatively treated solid abdominal organ injuries were also potential participants. The primary outcomes measured were thromboembolic events--either a documented lower extremity DVT by duplex color-flow doppler ultrasonography or a PE documented by rapid infusion CT pulmonary angiography or conventional pulmonary angiography. RESULTS: There were 118 patients enrolled in the study. Two patients (2%) developed DVT, one of which was proximal to the calf (95% confidence interval, 0% to 6%). Two of 12 patients (17%) with splenic injuries who received enoxaparin failed initial nonoperative management. There were no other bleeding complications, and no clinical evidence or documented episodes of PE. One patient died from multiple system organ failure. CONCLUSIONS: Enoxaparin is a practical and effective method for reducing the incidence of VTE in high risk, seriously injured patients. This study supports further investigation into the safety of enoxaparin prophylaxis in patients with closed head injuries and nonoperatively treated solid abdominal organ injuries.

Incidence of tracheal stenosis and other late complications after percutaneous tracheostomy.

OBJECTIVE: To determine the incidence of tracheal stenosis, voice and breathing changes, and stomal complications after percutaneous dilatational tracheostomy (PDT). METHODS: From December 1992 through June 1999, 420 critically ill patients underwent 422 PDTs. There were 340 (81%) long-term survivors, 100 (29%) of whom were interviewed and offered further evaluation by fiberoptic laryngotracheoscopy (FOL) and tracheal computed tomography (CT). Tracheal stenosis was defined as more than 10% tracheal narrowing on transaxial sections or coronal and sagittal reconstruction views. Forty-eight patients agreed to CT evaluation; 38 patients also underwent FOL. CT and FOL evaluations occurred at 30 +/- 25 (mean +/- standard deviation) months after PDT. RESULTS: Twenty-seven (27%) patients reported voice changes and 2 (2%) reported persistent severe hoarseness. Vocal cord abnormalities occurred in 4/38 (11%) patients, laryngeal granuloma in 1 (3%) patient, focal tracheal mucosal erythema in 2 (5%) patients, and severe tracheomalacia/stenosis in 1 (2.6%) patient. CT identified mild (11-25%) stenosis in 10 (21%) asymptomatic patients, moderate (26-50%) stenosis in 4 (8.3%) patients, 2 who were symptomatic, and severe (>50%) stenosis in 1 (2%) symptomatic patient. Ten patients (10%) reported persistent respiratory problems after tracheal decannulation, but only four agreed to be studied. Two patients had moderate stenosis, and one had severe stenosis. One patient's CT scan was normal. No long-term stomal complications were identified or reported. CONCLUSIONS: Subjective voice changes and tracheal abnormalities are common after endotracheal intubation followed by PDT. Long-term follow-up of critically ill patients identified a 31% rate of more than 10% tracheal stenosis after PDT. Symptomatic stenosis manifested by subjective respiratory symptoms after decannulation was found in 3 of 48 (6%) patients.

The safety of prolonging the use of central venous catheters: a prospective analysis of the effects of using antiseptic-bonded catheters with daily site care.

OBJECTIVE: To determine rates of catheter colonization and catheter-related bloodstream infection (CRBSI) when antiseptic-bonded central venous catheters (CVCs) and standardized daily site care are used with no predetermined interval for removal. DESIGN: Prospective observational study. SETTING: Two major trauma centers. PATIENTS: All trauma patients admitted to two major trauma centers that received a CVC from May 1996 through May 1998. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Catheters were semiquantitatively cultured to identify bacterial colonization and CRBSI. Monitored variables included total catheter days, anatomical site of catheter insertion, and area in hospital of catheter insertion. CVC tips and intracutaneous segments were semiquantitatively cultured. A total of 460 (92%) of 501 catheters placed in 324 trauma patients were evaluable, representing 95.5% of all catheter days during the study period. Rates of catheter colonization and CRBSI were 5% (5/1000 catheter days) and 1.5% (1.511000 catheter days), respectively. Subclavian catheters were in place longer than femoral or internal jugular catheters (p < .0001), but the colonization rate was significantly lower (p = .03; relative risk, 0.34; 95% confidence interval, 0.15-0.77). No differences in CRBSI rates among anatomical sites or between catheters used < or =14 days and those used >14 days were identified. CONCLUSION: Femoral and internal jugular antiseptic-bonded CVCs develop bacterial colonization earlier than subclavian CVCs. Subclavian antiseptic-bonded CVCs combined with standardized daily site care may be safely used >14 days in trauma patients.

Mechanisms and patterns of injuries related to large animals.

BACKGROUND: Injuries from encounters with large animals represent a significant health risk for rural communities. We evaluated our regional trauma centers' experience with large-animal injuries to determine whether certain mechanisms and patterns of injury predicted either major head/craniofacial or torso (chest/abdomen/pelvis) trauma. METHODS: The hospital courses of 145 patients with injuries related to large animals were reviewed retrospectively to determine patterns of injury, specific injury mechanisms, species-specific injuries, and predictors of multiple body region trauma. RESULTS: Seventy-nine patients (55%) were injured by horses, 47 patients (32%) by bulls, 16 patients (11%) by cows, and 3 patients (2%) by wild animal attacks. The predominant species-specific mechanisms of injury were falls (horses), tramplings (bulls), and kicks (cows). Brain/craniofacial injuries were most common from horse-related encounters (32%), whereas bull and cow encounters usually resulted in torso injuries (45% and 56%, respectively). Multiple body region injuries occurred in 32% of patients. Fractures of the upper extremities were more often associated with torso and head/craniofacial injuries (48%) than lower extremity injuries (17%) (p = 0.02). CONCLUSION: Large animal injuries frequently involve multiple body regions with species-specific mechanisms. Upper extremity injuries are associated with a significantly higher percentage of torso and head/craniofacial injuries, which may have implications for field triage.

Tyler asbestos workers: mortality experience in a cohort exposed to amosite.

OBJECTIVES: To examine the causes of death among 1130 former workers of a plant in Tyler, Texas dedicated to the manufacture of asbestos pipe insulation materials. This cohort is important and unusual because it used amosite as the only asbestiform mineral in the production process. High level exposure of such a specific type was documented through industrial hygiene surveys in the plant. METHODS: Deaths were ascertained through various sources including data tapes from the Texas Department of Health and the national death index files. As many death certificates as possible were secured (304/315) and cause of death assigned. After select exclusions, 222 death certificates were used in the analysis. Causes of death were compared with age, race, and sex specific mortalities for the United States population with a commercial software package (OCMAP Version 2.0). RESULTS: There was an excess of deaths from respiratory cancer including the bronchus, trachea, and lung (standardised mortality ratio (SMR) 277 with 95% confidence interval (95% CI) 193 to 385). Four pleural mesotheliomas and two peritoneal mesotheliomas were identified. The analysis also showed an increasing risk of respiratory malignancy with increased duration of exposure including a significant excess of total deaths from respiratory cancer with less than six months of work at the plant (SMR 268 with 95% CI 172 to 399). CONCLUSIONS: The importance of the cohort lies with the pure amosite exposure which took place in the plant and the extended period of latency which has followed. The death certificate analysis indicates the pathogenicity of amosite, the predominant commercial amphibole used in the United States. These data confirm a link between amosite asbestos and respiratory malignancy as well as mesothelioma.

Analysis of asbestos fiber burden in lung tissue from mesothelioma patients.

Mesothelioma is a rare neoplasm that occurs most frequently in individuals with previous asbestos exposure. Differences for risk of development of asbestos-related mesothelioma and lung cancer have been attributed to the various types of asbestos, as well as to the dimension of the inhaled fibers. In the present study, 55 individuals with the pathological diagnosis of mesothelioma were evaluated as to ferruginous body and fiber content in lung tissue. The procedures used in the analysis included tissue digestion and analysis of the collected material for ferruginous bodies by light microscopy and for uncoated fibers by analytical transmission electron microscopy. Forty-six of the samples had ferruginous body concentrations of over 1000/per gram dry weight of lung tissue. The majority of the cores of these ferruginous bodies were amosite. Likewise, the most common uncoated asbestos fiber in the tissue was amosite. Only a small percentage of each type of asbestos would have been visible by light microscopy or even potentially by electron microscopy if the magnification was not sufficient to detect those with thin (< 0.2 micron) diameters. The consistent finding in most of the cases was a considerable presence of asbestos, often of mixed types.

Motif identification neural design for rapid and sensitive protein family search.

The accelerated growth of the molecular sequencing data has generated a pressing need for advanced sequence annotation tools. This paper reports a new method, termed MOTIFIND (Motif Identification Neural Design), for rapid and sensitive protein family identification. The method is extended from our previous gene classification artificial neural system and employs two new designs to enhance the detection of distant relationships. These include an n-gram term weighting algorithm for extracting local motif patterns, and integrated neural networks for combining global and local sequence information. The system has been tested with three protein families of electron transferases, namely cytochrome c, cytochrome b and flavodoxin, with a 100% sensitivity and more than 99.6% specificity. The accuracy of MOTIFIND is comparable to the BLAST database search method, but its speed is more than 20 times faster. The system is much more robust than the PROSITE search which is based on simple signature patterns. MOTIFIND also compares favorably with the BLIMPS search of BLOCKS in detecting fragmentary sequences lacking complete motif regions. The method has the potential to become a full-scale database search and sequence analysis tool.

Beta-Carotene, vitamin A, and lung cancer chemoprevention: results of an intermediate endpoint study.

A randomized, placebo-controlled clinical trial of beta-carotene and retinol was conducted with 755 former asbestos workers as study subjects. The targeted endpoint for the intervention study was a reduction in the incidence and prevalence of sputum atypia. The dosage of 50 mg beta-carotene/d and 25,000 IU retinol/d on alternate days resulted significant increases in serum concentrations of both agents with no clinically significant toxicity. Skin yellowing was observed in approximately 35% of patients and may have contributed adversely to protocol adherence. Baseline analysis revealed that smoking and drinking were associated with lower concentrations of serum beta-carotene, even after dietary carotene intake was adjusted for (P < 0.0001). Baseline concentrations of retinol were apparently lowered by smoking (P < 0.002) and increased by drinking (P < 0.0001). Drinking and smoking also were significantly related to lower beta-carotene concentrations after supplementation (P < 0.001). No significant reduction in sputum atypia was observed after treatment.

Two biochemical markers effectively used to separate smokeless tobacco users from smokers and nonusers.

Data from asbestos workers were used to devise a cutpoint classifier to identify subjects as Nonuser (non-tobacco user), Smokeless (exclusive smokeless tobacco user), and Smoker (ignited tobacco user). In some clinical trials and smoking cessation programs, Smokeless should be separated from Smoker. One therefore needs a marker for smoke exposure, such as thiocyanate, since nicotine levels, as measured by cotinine, could be similar in both groups. Levels of cotinine (ng/mL) and thiocyanate (mumol/L) levels (mean +/- SD) were, respectively: 320.9 +/- 201.1 and 145.9 +/- 63.7 for the Smoker group; 339.1 +/- 327.5 and 32.0 +/- 16.9 for the Smokeless group; and 0.6 +/- 2.6 and 58.2 +/- 33.2 for the Nonuser group. For Nonuser, Smokeless, and Smoker, respectively, the self-reported status was 45.1%, 10.8%, and 44.1%, which was adjusted to 42.2%, 11.6%, and 46.2%; the classifier yielded sensitivities of 100%, 76.1%, and 92.2%; specificities of 96.1%, 97.6%, and 96.4%; and predictive values of 94.9%, 80.6%, and 95.6%. The classifier successfully identified Nonusers, separated Smokeless from Smoker, and determined the prevalence of false reports in our cohort.

Sputum cytology within and across laboratories. A reliability study.

A total of 11 cytotechnologists at sites in Texas (TX1, TX2), California (CA) and Arkansas (AR) were assessed for agreement of six-category diagnoses of sputum cytology slides prepared by the method of Saccomanno. For three observers at TX1 there was more agreement within observers (27-60%) than across observers (13-50%). Within-1 category intraobserver agreement underwent a twofold to threefold increase, to 77-93%; within-2 category agreement was 90-100%. Interobserver within-1 category agreement was 47-92%; within-2 category agreement was 83-100%. Agreement was significantly greater than chance (using kappa) in 69% of all intraobserver and interobserver pairings. Intralaboratory agreement was 40% for CA and 40-57% for TX2. Among pairings of the four sites, the range of interlaboratory agreement was 13-60% over several occasions. The overall range of agreement with the TX1 standard was 17-50% over observers/occasions. Within certain categories, outside agreement with the TX1 standard was 53-90% for normal, 39-80% for squamous metaplasia, 68-84% for mild atypia, 80-100% for moderate atypia and 93-100% for severe atypia or carcinoma. We conclude that agreement is acceptable for extreme atypia, but more training or refinement of the guidelines may be needed, if justified, to better differentiate the lowest categories. Good agreement appears to be as likely for observers with many years of overall experience as for those with high exposure to the Saccomanno method. For potential statistical analyses, the scale should probably be condensed into three to four categories to reduce extraneous variability.

Identifying disagreement in ordinal ratings within a fixed panel of cytotechnologists.

In many clinical settings, a fixed number of raters screen specimens with more than two ordinal outcomes (for example, mild, moderate, severe). A design is proposed that facilitates the measurement of both interrater and intrarater agreement and associated trends. Design deficiencies are discussed, as are the propriety and interpretation of some common indices of reliability and reproducibility. The concepts are illustrated with data from cytopathologic ratings for sputum light microscopy.

Initial clinical assessment of the comatose patient: cerebral malaria vs. meningitis.

One hundred twenty-one Liberian children were admitted in coma to the ELWA Hospital, Monrovia, Liberia. Admitting diagnoses, before lumbar puncture, were compared with discharge diagnoses. Ninety-four children were discharged with a final diagnosis of cerebral malaria and 27 with a diagnosis of meningitis. The admitting diagnosis was correct in 76.6% (72 of 94) of patients with cerebral malaria and 59.3% (16 of 27) of patients with meningitis. The cerebrospinal fluid leukocyte count was the single most significant factor in determining the correct diagnosis. Without the cerebrospinal fluid analysis, the discriminant accuracy (77%), i.e. definitive separation of the two illnesses, was comparable to the physician's admission diagnosis (73%). Other data contributing to the differential diagnosis of cerebral malaria and meningitis included the number of days of fever before admission, the presence or absence of nuchal rigidity, fontanelle fullness and peripheral blood malaria smear. Mortality rates for cerebral malaria and meningitis were 14.9 and 29.6%, respectively. These data suggest that physicians cannot reliably discriminate between cerebral malaria and meningitis without cerebrospinal fluid analysis.

Conventional respiratory cytology versus fine needle aspiration cytology in the diagnosis of lung cancer.

The results of 184 fine needle aspiration (FNA) cytologic examinations were compared with the findings of "conventional" respiratory cytology (on sputums, bronchial brushings and bronchial washings) and histology (on biopsy and autopsy samples) and with the medical records. Positive cytologic results were obtained in 6 (10%) of 60 sputums, 17 (21%) of 80 brushings, 16 (19%) of 84 washings and 82 (44%) of 184 aspirates. These positive results were confirmed by biopsy for 6 of 6 sputums, 16 of 17 brushings and 15 of 16 washings. Among the 82 patients with a positive FNA cytology, malignancy was confirmed by lung biopsy in 39 and by autopsy in 2; the cytologic diagnosis was supported by clinical and radiographic findings in all but 1 of the remaining 41 patients. Using transbronchial lung biopsy, autopsy and medical records as final standards, the positive predictive values were 100% for sputum, 94.1% for brushings, 93.0% for washings and 98.6% for FNA samples. The high positive predictive values of FNA and the other cytologic procedures indicate that these diagnostic modalities provide simple, rapid and reliable methods for the diagnosis of lung cancer.

Changing utilization of cytopathology versus histopathology in the diagnosis of lung cancer.

We studied the utilization rates of 1) cytopathology procedures [sputum, fine-needle aspirates (FNA), bronchial washings and brushings] versus 2) histopathology procedures (bronchial biopsies, lymph node biopsies, lobectomies, pneumonectomies) in the diagnosis of lung cancer, over two time periods (1967/1987). Comparisons were made in the utilization rates of these two diagnostic procedures in two groups of 100 patients each. Statistically significant changes included 1) an increase of cytopathology procedures, as the sole means of diagnosis; 2) an increase in FNAs; 3) an increased percentage of positive cytopathologic diagnosis; and 4) a decrease of major surgical procedures (lobectomy, pneumonectomy), as means of initial pathologic diagnosis. This study provides data supporting the trend of decreasing surgical procedures for initial diagnosis of lung cancer, with greater, more effective utilization of cytopathologic (particularly FNA) procedures.

Usefulness of combined light and electron microscopy: evaluation of sputum samples for asbestos to determine past occupational exposure.

Ferruginous bodies (FB) in sputa are recognized as an indicator of past exposure to asbestos. However, a great variability exists in FB production, even in individuals with a history of occupational exposure. A further complication in interpreting the presence of FBs in sputa is that all individuals in modern society are exposed to asbestos and, in lung tissue studies, have been shown to harbor appreciable numbers of asbestos fibers. Thus, some of these individuals should occasionally produce FBs in their sputa. The present study was undertaken to determine if uncoated asbestos fiber content could be used to better discriminate occupationally exposed individuals from the general population. Randomly selected sputum samples from 12 former workers in an amosite asbestos plant and 12 controls were studied. The samples were prepared for the study by digesting the sputa in sodium hypochlorite. The digests were filtered through 0.2-microns polycarbonate filters for collection of particulates. The filters were screened for FBs by light microscopy at 200 X, and the presence or absence of uncoated asbestos fibers was determined at 5000 X in an AMRAY 1000A scanning electron microscope. The use of electron microscopy revealed the presence of commercial amphiboles in the sputa of the occupationally exposed individuals and enabled a differentiation of these samples from those of the general population.

Comparison of three tracers for detecting lung epithelial injury in anesthetized sheep.

We compared the ability of three aerosolized tracers to discriminate among control, lung inflation with a positive end expired pressure of 10 cmH2O, lung vascular hypertension and edema without lung injury, and lung edema with lung injury due to intravenous oleic acid. The tracers were 99mTc-diethylenetriaminepentaacetate (99mTc-DTPA, mol wt 492), 99mTc-human serum albumin (99mTc-ALB, mol wt 69,000), and 99mTc-aggregated albumin (99mTc-AGG ALB, mol wt 383,000). 99mTc-DTPA clearance measurements were not able to discriminate lung injury from lung inflation. The 99mTc-AGG ALB clearance rate was unchanged by lung inflation and increased slightly with lung injury. The 99mTc-ALB clearance rate (0.06 +/- 0.02%/min) was unchanged by lung inflation (0.09 +/- 0.02%/min, P greater than 0.05) or 4 h of hypertension without injury (0.09 +/- 0.04%/min, P greater than 0.05). Deposition of 99mTc-ALB within 15 min of the administration of the oleic acid increased the clearance rate to 0.19 +/- 0.06%/min, which correlated well with the postmortem lung water volume (r = 0.92, P less than 0.01). This did not occur when there was a 60-min delay in the deposition of 99mTc-ALB. We conclude that 99mTc-ALB is the best indicator for studying the effects of lung epithelial injury on protein and fluid transport into and out of the air spaces of the lungs in a minimally invasive manner.

Effects of lung volume on clearance of solutes from the air spaces of lungs.

Several investigators have shown that the clearance rate of aerosolized 99mTc-labeled diethylenetriamine pentaacetate (DTPA, mol wt = 492, radius = 0.6 nm) from the air spaces of the lungs of humans and experimental animals increases with lung volume. To further investigate this phenomenon we performed a compartmental analysis of the 2-h clearance of DTPA from the lungs of anesthetized sheep using a new method to more accurately correct for the effects of DTPA recirculation. This analysis showed that the DTPA clearance in eight sheep ventilated with zero end-expired pressure was best described by a one-compartment model with a clearance rate of 0.42 +/- 0.15%/min. Ventilating eight sheep with an end-expired pressure of 10 cmH2O throughout the study increased the end-expired volume 0.4 +/- 0.1 liter BTPS and created a clearance curve that was best described by a two-compartment model. In these sheep 56 +/- 16% of the DTPA cleared from the lungs at a rate of 7.9 +/- 2.9%/min. The remainder cleared at a rate similar to that measured in the sheep ventilated with zero end-expired pressure (0.35 +/- 0.18%/min). Additional control and lung inflation experiments were performed using 99mTc-labeled human serum albumin (mol wt = 66,000, radius = 3.6 nm). In six control sheep ventilated with zero end-expired pressure the albumin clearance was best described by a one-compartment model with a clearance rate of 0.06 +/- 0.02%/min. The clearance rate in six sheep with increased lung volume was slightly larger (0.09 +/- 0.02, P less than 0.05) but was well described by a one-compartment model.(ABSTRACT TRUNCATED AT 250 WORDS)