Armies of pestilence: CNS infections as potential weapons of mass destruction.

Infectious agents have been investigated, developed, and used by both governments and terrorist groups as weapons of mass destruction. CNS infections, though traditionally considered less often than respiratory diseases in this scenario, may be very important. Viruses responsible for encephalitides can be highly infectious in aerosol form. CNS involvement in anthrax is ominous but should change treatment. Brucellosis, plague, Q fever, and other bacteria can uncommonly manifest with meningoencephalitis and other findings. Emerging diseases may also pose threats. We review infectious agents of particular concern for purposes of biowarfare with respect to CNS manifestations and imaging features.

The course of nosocomial oropharyngeal colonization in patients recovering from acute respiratory failure.

We sought to determine the duration of nosocomially acquired Gram-negative bacilli (GNB) oropharyngeal colonization following hospitalization for acute respiratory failure (ARF). We selected 24 inpatients recovering from ARF who had positive oropharyngeal cultures for GNB. Follow-up cultures were obtained at the time of hospital discharge, and 2 and 4 weeks afterwards. The prevalence of GNB colonization in these patients was 14/21 (67 percent) at the time of hospital discharge and 14/23 (60 percent) 2 weeks afterwards. Both rates were greater than the control population's 7/30 (23 percent, p < 0.02 and < 0.05, respectively). Four weeks after hospital discharge, the prevalence of colonization had fallen to 7/19 (37 percent) which was not significantly different from that of controls. Five of 24 subjects were rehospitalized during the follow-up period. Pneumonia was diagnosed in only two of the five and both proved to be due to pathogens other than GNB. We conclude that the prevalence of GNB oropharyngeal colonization following ARF approaches control levels within four weeks of hospital discharge. We speculate that a post-ARF patient's risk for GNB pneumonia similarly declines.

Small nodules detected on chest radiography: does size predict calcification?

STUDY OBJECTIVES: To determine whether the likelihood of lung nodule calcification can be predicted from nodule size as measured on a chest radiograph (CXR). DESIGN: Retrospective review of CXRs of patients with lung nodules < or =1 cm in size detected on CT scanning. CT images were used to identify calcifications and to provide spatial localization for readers to visualize nodules on a CXR and to measure their size. A subset of these nodules then was reexamined by different readers who did not view the CT scans SETTING: Two university hospitals (Albuquerque, NM; Dallas, TX) and a US Air Force/Veterans Administration medical center (Albuquerque, NM). PATIENTS: Two hundred thirty-six nodules in 185 patients RESULTS: One half of the nodules (118) seen on CT scans could not be located on CXR, of which 8 (7%) were calcified. The prevalence of calcifications in the other 118 nodules visualized on CXRs was much higher (71 of 118 nodules [60%]; p<0.005). Among the nodules visualized on CXRs, those < 7 mm in diameter (44 of 57 nodules [77%]) were more likely to be calcified than those > or = 7 mm in diameter (27 of 61 nodules [44%]; p<0.005). Radiographs of 42 of the smallest nodules visualized on CXRs by the initial readers later were examined prospectively by different readers who did not have access to the CT images. Thirty of 33 of the calcified nodules (91%) but only 3 of 9 of the noncalcified nodules (33%) were detected (p<0.005). These readers also recorded 40 additional small nodules that were not seen on CT scans, which were considered to be false-positives. CONCLUSIONS: Nodules detected on CXRs that measure <7 mm in size are likely to be calcified or to represent a false-positive finding.

Tissue release of adenosine triphosphate degradation products during shock in dogs.

Clinical monitoring of cellular metabolism during shock, based largely on traditional metabolic indicators, remains unsatisfactory. The purpose of this study was to compare venous oxygen tension and blood lactate gradients with blood gradients of purine nucleotide degradation products which are derived from tissue ATP catabolism during hypovolemic shock. Sixteen dogs were instrumented to sample arterial and venous blood. Measurements of arteriovenous lactate and PNDP gradients during spontaneous respiration were examined at four tissue sites: gut, kidney, hindlimb, and diaphragm. Hypovolemic shock (mean arterial blood pressure 35 to 40 mm Hg) was induced and maintained for one hour. The above parameters were remeasured at 30 and 60 minutes after induction of shock. Hypoxanthine gradients were greater than that of other PNDP, and so were used as the primary indicator of tissue ATP metabolism. In the hindlimb, the mean AV gradients for hypoxanthine (1 +/- 1 microM) were not significantly greater than baseline, while the lactate gradient (700 +/- 300 microM) rose markedly. In contrast, across the kidney there was a significantly greater AV hypoxanthine gradient (16 +/- 3 microM, p less than 0.002) but no lactate gradient (-400 +/- 200 microM). Both the hypoxanthine and lactate AV gradients were significantly elevated across the diaphragm and gut. Venous PO2 values less than 35 mm Hg predicted an increased hypoxanthine gradient across the kidney, but not across the hindlimb. We conclude that the metabolic response to hypovolemic shock as assessed by PNDP gradients, lactate gradients, and venous PO2 differs among tissues. Although resting muscle such as the hindlimb may be an important source of blood lactate, the viscera and working skeletal muscle (the diaphragm) are major contributors to circulating PNDP.

Air embolus complicating transthoracic percutaneous needle biopsy.

Transthoracic percutaneous needle biopsy has become popular for evaluation of pulmonary nodules. However, it is a procedure with morbidity and mortality that is not negligible. In this article, we report massive air embolus complicating needle biopsy in a patient with amyloidosis. A negative biopsy does not exclude malignancy, and if surgical excision will be performed regardless of the result, preoperative assessment using this technique may not be necessary.

Pulmonary delivery of nanoparticles of insoluble, iodinated CT X-ray contrast agents to lung draining lymph nodes in dogs.

Lung cancer continues to be a leading cause of death around the world. Staging of this disease is critically dependent upon the involvement or noninvolvement of the lymph nodes which drain the region of lung containing the lesion/tumor. Palpation, unenhanced CT, and lymph node excision (i.e., mediastinectomy) are currently used to ascertain the status of these regional draining lymph nodes. The work reported herein details the first efforts toward the pulmonary instillation of iodinated nanoparticles for contrast-enhanced CT of lung draining lymph nodes. The data reflect the impact of dose, time post instillation, and formulation (surfactant) upon the observed CT enhancement of the tracheobronchial lymph nodes of beagle dogs. In addition, initial safety is discussed with both macroscopic and microscopic observations. The results indicate that pulmonary instillation of small volumes of iodinated nanoparticles could be successfully used to aid staging of lung cancer by CT imaging.

Is the stat Gram stain helpful during percutaneous image-guided fluid drainage?

RATIONALE AND OBJECTIVES: The purpose of this study was to use logistic regression to analyze both Gram stain results and other clinical information to create a decision rule capable of predicting which abdominal or pelvic fluid collections would later prove to be infected and therefore require catheter drainage. MATERIALS AND METHODS: The authors retrospectively collected Gram stain results and clinical data (postoperative status and antibiotic use) regarding 124 abdominal or pelvic fluid drainage procedures performed between 1991 and 1996. They then analyzed these data by using logistic regression to create an equation that predicted the presence of fluid infection. Finally, they validated this equation by applying it to 39 abdominal or pelvic fluid drainage procedures performed in 1997. RESULTS: The resulting equation predicted that a fluid collection was likely to be infected if any of the following were present: Gram stain positive for bacteria, Gram stain showing moderate or many white blood cells, and purulent fluid at visual inspection. For the initial data set, the sensitivity of the decision rule was 91%, the specificity was 54%, and the overall accuracy was 77%. For the 1997 data set, the sensitivity of the decision rule was 88%, the specificity was 50%, and the accuracy was 77%. CONCLUSION: When combined with clinical information, Gram stain results are sensitive but nonspecific in the detection of abdominal or pelvic fluid infection. Use of the decision rule could prevent unnecessary catheter placement in a minority of patients with abdominal or pelvic fluid collections.

Thin-section CT evidence of bronchial thickening in children with stable asthma: bronchoconstriction or airway remodeling?

RATIONALE AND OBJECTIVES: The authors performed this study to determine if bronchial wall thickening is present in children with moderate to severe asthma during periods free from clinical bronchoconstriction. MATERIALS AND METHODS: The authors obtained low (radiation) dose thin-section computed tomographic (CT) scans in each of 18 control subjects and 21 children with moderately severe but stable asthma. Spirometry was performed on all subjects at the time of CT scanning. Bronchial wall thickness and bronchial wall area were measured, and the percentage wall area (bronchial wall area divided by bronchial cross-sectional area) was calculated. The authors performed best-fit regression analysis of wall thickness and percentage wall area versus bronchial diameter and qualitative analysis of images for bronchial wall thickening. RESULTS: In asthmatic patients, the mean percentage of the predicted forced expiratory volume in 1 second was 0.88 +/- 0.09. The best fit regression line that demonstrated the relationship between wall thickness and bronchial diameter for patients with asthma differed significantly from that for control subjects (P < .005). The regression line that demonstrated the relationship between the percentage wall area and bronchial diameter for patients with asthma differed from that of the control subjects when bronchial wall thickness measurements were used to calculate the percentage wall area (P < .05). Results of qualitative analysis also showed significantly more bronchial wall thickening in asthmatic patients than in control subjects (P < .001). CONCLUSION: Bronchial wall thickening detected at thin-section CT in children with moderately severe asthma cannot be attributed solely to bronchoconstriction and may represent airway inflammation or remodeling.

CT imaging of intrathoracic lymph nodes in dogs with bronchoscopically administered iodinated nanoparticles.

RATIONALE AND OBJECTIVES: The purpose of the study was to determine if airway instillation of iodinated nanoparticles results in contrast material enhancement of tracheobronchial lymph nodes in dogs. MATERIALS AND METHODS: Eight dogs underwent intrabronchial instillation of iodinated nanoparticles; six dogs received 900 mg each, and two dogs received 450 mg each. Spiral computed tomography (CT) was then performed 2-34 days later. RESULTS: CT scans obtained 2 days after instillation showed the presence of contrast material within the lung parenchyma but no nodal enhancement. Scans obtained 6-34 days after instillation showed enhancement of the right, left, and middle tracheobronchial lymph nodes (analogous to the mediastinal nodes in humans). Mean nodal attenuation on CT images was 117 HU +/- 43, and the mean nodal volume was 129 mm3 +/- 113. Histologic specimens of the nodes showed macrophage hyperplasia. CONCLUSION: Iodinated nanoparticles instilled into small airways are transported to the tracheobronchial lymph nodes, where they result in contrast enhancement.

A new view of pulmonary edema and acute respiratory distress syndrome.

The old division of lung edema into two categories--cardiogenic (hydrostatic) and noncardiogenic (increased permeability)--is no longer adequate. For instance, it fails to distinguish between the capillary leak caused by acute respiratory distress syndrome from that caused by interleukin-2 treatment. Further, it fails to account for the capillary leak ('stress-failure') that may accompany edema. A modern view of edema must recognize the natural barriers to the formation and spread of edema. These barriers are the capillary endothelium and the alveolar epithelium. Varying degrees of damage to them can account for the varying radiographic and clinical manifestations of lung edema. Thus, interleukin-2 administration causes increased endothelial permeability without causing alveolar epithelial damage. The result is lung edema that is largely confined to the interstitium, causing little hypoxia and clearing rapidly. However, acute respiratory distress syndrome, which is characterized by extensive alveolar damage, causes air-space consolidation, severe hypoxia, and slow resolution. Thus, a reasonable classification of lung edema requires at least four categories: 1) hydrostatic edema; 2) acute respiratory distress syndrome (permeability edema caused by diffuse alveolar damage); 3) permeability edema without alveolar damage; and (4) mixed hydrostatic and permeability edema. The authors emphasize the importance of the barriers provided by the capillary endothelium and the alveolar epithelium in determining the clinical and radiographic manifestations of edema. In general, when the alveolar epithelium is intact, the radiographic manifestations are those of interstitial (not air-space) edema; this radiographic pattern predicts a mild clinical course and prompt resolution.

Nonaortic mediastinal injuries from blunt chest trauma.

In addition to traumatic aortic injuries (TAI), blunt chest trauma may damage other structures in the mediastinum, including the tracheobronchial tree, the heart and pericardium, and rarely the esophagus. Tracheobronchial injuries may be difficult to separate radiographically from accompanying parenchymal lung injuries. Experience with diagnosis by computed tomography (CT) is still limited. Cardiac injuries often require emergent surgery before extensive imaging can be done. Some patients, usually those with chamber ruptures of the right heart, survive long enough to receive a chest CT, at which time hemopericardium can be detected. Upper esophageal injuries may occur in conjunction with lower cervical or upper thoracic spine injures. Distal esophageal injuries are rarely caused by blunt trauma.

Distinguishing hantavirus pulmonary syndrome from acute respiratory distress syndrome by chest radiography: are there different radiographic manifestations of increased alveolar permeability?

Hantavirus infection may cause diffuse air space disease, termed hantavirus pulmonary syndrome (HPS). The authors sought to determine if chest radiographs could differentiate HPS from typical acute respiratory distress syndrome (ARDS). The authors identified patients with either HPS (n = 11) or acute ARDS (n = 32) and selected the earliest chest radiograph showing diffuse airspace disease, and a chest radiograph taken 24 to 48 hours previously. Thoracic and general radiologists first viewed the chest radiograph showing diffuse air space disease, and ranked the likelihood that each case represented HPS versus ARDS. Afterward, readers viewed earlier chest radiographs and rescored each case. Receiver operating characteristic (ROC) curves from both scoring sessions were generated. The mean areas under the ROC curves for the entire group was 0.83 +/- 0.12 initially, and improved to 0.87 +/- 0.09 (p < 0.05) after viewing prior chest radiographs. Receiver operating characteristic curves of thoracic radiologists described greater areas than those of general radiologists both before and after viewing prior chest radiographs; 0.95 +/- 0.01 versus 0.78 +/- 0.08 (p < 0.05) and 96 +/- 0.02 versus 0.80 +/- 0.05 (p < 0.05). The mean sensitivity and specificity of chest radiograph interpretation for HPS was 86 +/- 13% and 74 +/- 11%, respectively. Chest radiographs can differentiate HPS from ARDS. Accuracy is improved by the use of serial radiographs and more highly trained readers. The chest radiograph findings may represent differences in the extent of alveolar epithelial damage seen in HPS and ARDS.

Potential uses of computed tomography-SPECT and computed tomography-coincidence fusion images of the chest.

The ability to fuse (or merge) data sets from SPECT and coincidence nuclear medicine scans with computed tomographic images combines physiologic information from the former method with the superior anatomic resolution of the latter technique. In many cases, this allows more definitive diagnosis than can be obtained by simple visual comparison of nuclear medicine images and conventional cross-sectional imaging. The technique may be used in the staging and follow-up of lung carcinoma, pulmonary carcinoid, and lymphoma. It may also aid in the interpretation of perfusion defects in Tc-99m MAA lung scanning, aid in the interpretation of ground-glass opacity in selected cases of chest high-resolution computed tomography, and aid in the diagnosis of some mediastinal masses (e.g., intrathoracic goiters). In this nuclear medicine atlas, the method used to create fusion images in the chest is described, and examples of fusion imaging with radiopharmaceuticals are given that may be of clinical use in chest disease.

Detection of pulmonary emboli and associated right heart dysfunction by combining ventilation perfusion lung scanning and xenon ventriculography.

PURPOSE: The authors sought to determine if the right ventricular ejection fraction (RVEF), as measured by xenon ventriculography, is depressed in patients with pulmonary emboli. The authors also sought to correlate any decrement in RVEF with the extent of lung perfusion defects. MATERIALS AND METHODS: The authors identified all patients who had lung ventilation-perfusion (V/Q) scans between January 1994 and December 1996, that were interpreted as high probability for pulmonary embolism. From these patients, the authors selected those who had undergone concurrent xenon ventriculography (XV) (n = 23), and then reprocessed the initial ventriculography data for confirmation. The authors also reviewed original V/Q scans, chest radiographs, and clinical data. A control group was drawn from patients with normal V/Q scans who had undergone XV. RESULTS: Fifteen patients (65%) with high probability V/Q scans had an abnormally low RVEF (< .32). Patients with high probability V/Q scans also had a significantly lower mean RVEF (0.28 +/- .08) than patients with normal V/Q scans (.39 +/- .08 SD). The degree of RVEF decline correlated poorly with the number of segmental perfusion defects (r = -.39). CONCLUSIONS: RVEF is often depressed in patients with high probability V/Q scans. XV can identify these patients, while routine lung V/Q scans cannot.

C3a and adult respiratory distress syndrome after massive transfusion.

We compared the degree of complement activation in 15 patients receiving massive blood transfusions and 21 patients with the septic syndrome and examined its association with other risk factors for adult respiratory distress syndrome (ARDS). Patients with massive transfusion (n = 8) as their only risk factor for ARDS had lower C3a levels (250 +/- 80 ng/ml) and a lower incidence of ARDS (0%) than patients with massive transfusion plus other risk factors (n = 7; C3a, 600 +/- 120 ng/ml; ARDS, 55%) or patients with the septic syndrome (n = 21; C3a, 540 +/- 80 ng/ml; ARDS, 19%). In our patients, the degree of complement activation appeared to reflect the presence of complicating clinical conditions.

Esophageal rupture after regional anesthesia: report of two cases.

Esophageal perforation after anesthesia is rare. It is usually secondary to esophageal instrumentation. Only one case of barogenic rupture after regional anesthesia has been reported. We report two additional cases and present possible mechanisms for this unusual entity. Neither patient had anatomic abnormalities by history or preoperative endoscopy. However, both patients and the previously reported patient had esophageal dysmotility resulting from advanced age, alcoholism, intraoperative medications, and preexisting disease. Each patient experienced at least one episode of emesis with subsequent perforation of the distal one third of the esophagus. The previously reported patient died; both of our patients underwent successful surgical repair and are alive 2 years later. Intraoperative or postoperative emesis in patients with esophageal dysmotility appears to be the principal factor causing esophageal rupture after regional anesthesia. Prevention of nausea and vomiting and recognition of this high-risk population may minimize this complication in the future.

Plasma hypoxanthine and exercise.

During exercise, ATP is converted to ADP and AMP to supply energy for muscular contraction. It is then regenerated via various pathways of intermediary metabolism. However, with high levels of exercise, net ATP degradation in muscle occurs. In exercise and other clinical situations, adenine nucleotide degradation leads to an accumulation of degradative purine products including hypoxanthine. In an effort to monitor events of energy metabolism, we examined plasma hypoxanthine levels at various exercise intensities. Peak plasma hypoxanthine levels after maximal exercise (18.9 +/- 2.6 microM, mean +/- SEM) were significantly greater than resting levels (1.1 +/- 0.1 microM; p less than 0.001). Hypoxanthine levels after steady state exercise at 52, 76, and 97% of ventilatory threshold did not exceed resting levels. However, plasma hypoxanthine rose significantly after exercise at 124% of ventilatory threshold (6.3 +/- 1.0 microM; p less than 0.01) and at 152% of ventilatory threshold (17.0 +/- 3.6 microM; p less than 0.001). Exercise at subventilatory threshold intensity (74% of ventilatory threshold) for a prolonged time period, such that total work equaled that performed at 152% of ventilatory threshold, did not elevate hypoxanthine levels (0.46 +/- 0.1 microM) above resting values. We conclude that elevation of plasma hypoxanthine levels occur during exercise at intensities that exceed the ventilatory threshold and indicate that net adenine nucleotide degradation has occurred.

Purine efflux after cardiac ischemia: relevance to allopurinol cardioprotection.

Allopurinol is thought to protect hearts against damage due to hypoxia or ischemia by inhibiting xanthine oxidase and oxygen radical generation. We subjected isolated rabbit hearts, equilibrated by perfusion at 37 degrees C, to 1 h of global ischemia at 27 or 37 degrees C with or without brief pretreatment with 100 microM allopurinol. The total absence of xanthine or uric acid in the coronary effluent following ischemia, the presence of hypoxanthine (25 +/- 4 microM peak concentration), and the failure of allopurinol to alter purine washout profiles or postischemic cardiac function suggest that rabbit myocardium lacks xanthine oxidase or dehydrogenase. Data obtained with a similar rat heart preparation showed appreciable formation of xanthine (12 +/- 2 microM peak) and uric acid (10 +/- 3 microM). Allopurinol pretreatment inhibited xanthine and uric acid formation and significantly improved key indicators of postischemic left ventricular function. We conclude that there is species dependency in the myocardial activity of xanthine oxidase or dehydrogenase, that when present it can be inhibited by acute allopurinol pretreatment, and that xanthine oxidase activity and its ability to generate oxygen radicals are not universal contributors to cardiac ischemic damage.