Pleural fluid characteristics in hantavirus pulmonary syndrome

Hantavirus pulmonary syndrome (HPS), is a rodent-borne, acute, often fulminant cardiorespiratory illness. Noncardiogenic pulmonary edema is prominent in HPS as is cardiac dysfunction. Pleural effusions are commonly noted in patients with HPS and have been thought to be exudative. This report describes the prevalence and characteristics of pleural effusions by an assessment of chest radiographs for the presence of pleural fluid and reviews all pleural fluid specimens obtained from patients with HPS. Of 23 patients treated at the University of New Mexico Hospital for HPS, 22 had evidence of pleural fluid while 4 had sampling of their pleural fluid. Two samples met criteria for an exudate by pleural fluid protein to serum protein ratio of more than 0.5; one was clearly a transudate and the other had inconsistent characteristics. The two exudative samples were obtained 7 days after admission, while the other 2 were obtained within 1 day of admission. Pleural fluid cultures were sterile, and the total of nucleated cells was less than 170/mm3, and predominately mononuclear. A hypothesis may be formulated that the pleural fluid in HPS is initially transudative, consistent with the observed cardiopulmonary dysfunction. However, following aggressive resuscitative efforts and as the acute illness resolves, fluid shifts occur as cardiac function normalizes; the pleural fluid may take on characteristics of an exudate.     

An outbreak of hantavirus pulmonary syndrome, Chile, 1997

A novel splice variant of RGS 9 was isolated from a rat hypothalamus, human retina, and a human kidney (Wilm's) tumor. This variant, termed RGS 9L, differs from the retinal form (termed RGS 9S) identified previously in that it contains a 211- (rat) or 205- (human) amino acid proline-rich domain on the carboxyl terminus. The pattern of RGS 9 mRNA splicing was tissue specific, with striatum, hypothalamus- and nucleus accumbens expressing RGS 9L, whereas retina and pineal expressed RGS 9S almost exclusively. This pattern of mRNA splicing seemed to be highly conserved between human and rodents, suggesting cell-specific differences in the function of these variants. Transient expression of RGS 9L augmented basal and beta-adrenergic receptor-stimulated adenylyl cyclase activity while suppressing dopamine D2 receptor-mediated inhibition. Furthermore, RGS 9L expression greatly accelerated the decay of dopamine D2 receptor-induced GIRK current. These results indicate RGS 9L inhibits heterotrimeric Gi function in vivo, probably by acting as a GTPase-activating protein. The human RGS 9 gene was localized to chromosome 17 q23-24 by radiation hybrid and fluorescent in situ hybridization analyses. The RGS 9 gene is within a previously defined locus for retinitis pigmentosa (RP 17), a disease that has been linked to genes in the rhodopsin/transducin/cGMP signaling pathway.     

Elevated levels of lung surfactant protein A in sera from patients with idiopathic pulmonary fibrosis and pulmonary alveolar proteinosis

An enzyme-linked immunosorbent assay using monoclonal antibodies to human lung surfactant protein A (SP-A) was applied to sera from patients with lung diseases. We examined whether SP-A appears in the sera of patients with diseases that are known to cause alterations in surfactant composition in bronchoalveolar lavage fluids, and we characterized the SP-A that was found. The level of SP-A in sera from 57 healthy volunteers was 45 +/- 3 ng/ml (mean +/- SEM). The levels in patients with idiopathic pulmonary fibrosis (IPF) (205 +/- 23 ng/ml, n = 32) and pulmonary alveolar proteinosis (PAP) (285 +/- 23 ng/ml, n = 6) were significantly higher than those in healthy control subjects (p < 0.01), whereas those of sarcoidosis (n = 16), pneumonia (n = 14), and tuberculosis (n = 14) were 52 +/- 27 ng/ml, 65 +/- 11 ng/ml, and 49 +/- 23 ng/ml, respectively. Electrophoresis and immunoblotting analysis demonstrated that the fraction isolated from serum of a patient with PAP or IPF by anti-SP-A immunoaffinity column chromatography consisted chiefly of human IgG and IgM, and that it also contained SP-A. Furthermore, IgG was found in preparation of purified human SP-A. SP-A was demonstrated to bind to nonimmune IgG coated onto microtiter wells. Gel filtration analysis revealed that serum SP-A was eluted at fractions of larger molecular size than was the purified SP-A. These findings suggest that SP-A appears in the bloodstream as a complex with immunoglobulin in IPF and in PAP.     

Serum levels of interleukin 6 in patients with lung cancer

Serum interleukin 6 (IL-6) levels were measured in 75 patients with lung cancer and in 20 patients with benign lung diseases. IL-6 was detectable in 29 patients with lung cancer (39%), but was not detectable in any of the patients with benign lung diseases. Serum C-reactive protein levels and plasma fibrinogen levels were significantly higher and serum albumin concentration was significantly lower in lung cancer patients with detectable serum IL-6 levels than in those without detectable serum IL-6 levels and in patients with benign lung diseases. On the other hand, no significant difference was observed in blood platelet counts in these three groups. Moreover, serum IL-6 levels were not significantly different in lung cancer patients with or without clinically demonstrated distant metastasis. These results suggest that IL-6 may be a mediator of various reactions including an inflammatory response in lung cancer patients.     

High levels of interleukin-8 in the blood and alveolar spaces of patients with pneumonia and adult respiratory distress syndrome

There is ample experimental evidence that polymorphonuclear neutrophils (PMN) play a critical role in the pathogenesis of the adult respiratory distress syndrome (ARDS). Since interleukin-8 (IL-8) is a strong chemotactic factor for PMN, we measured IL-8 levels in plasma and bronchoalveolar lavage (BAL) fluid of 18 patients, 12 with ARDS and 6 with severe pneumonia uncomplicated by ARDS, all of whom had an increased number of PMN in BAL fluid. Seven healthy subjects served as controls. We found elevated levels of IL-8 in the alveolar spaces of all patients tested. Elevated BAL IL-8 levels were related to a fatal outcome and the presence of shock and correlated with a general clinical severity index (simplified acute physiological score). BAL fluid levels of IL-8 were significantly higher in patients with ARDS than in patients with pneumonia. In plasma, IL-8 levels were increased similarly in all patients and did not correlate with survival or the presence of shock. The BAL fluid-to-plasma ratio of IL-8 was significantly greater than that of tumor necrosis factor alpha, indicating higher local production of IL-8. Moreover, the presence of a primed subpopulation of blood PMN with respect to H2O2 production indicates that IL-8 may contribute to the neutrophil-mediated process in the pathogenesis of ARDS and pneumonia.     

False-positive cytological diagnosis of lung carcinoma in patients with pulmonary infarcts

Cytological examination of specimens obtained from the tracheobronchial tree has become an integral part of the evaluation of pulmonary lesions. Cytological criteria for the diagnosis of carcinoma exist and are well defined. Certain benign processes, however, may possess features strongly suggestive of carcinoma of the lung. We report 3 patients in whom a positive cytological diagnosis of carcinoma of the lung was made by an experienced cytopathologist. At operation each patient was found to have pulmonary infarct and no evidence of carcinoma. Review of this experience has disclosed cytological and clinical features that should alert the clinician to the possibility that the cytological diagnosis of lung cancer may be misleading in certain nonmalignant diseases.     

Bayou virus-associated hantavirus pulmonary syndrome in Eastern Texas: identification of the rice rat, Oryzomys palustris, as reservoir host

OBJECTIVE: To validate the safety of gadolinium-diethylenetriamine pentaacetic acid (GD-DTPA) by measuring its effect on pancreatic capillary perfusion and acinar injury in acute pancreatitis. BACKGROUND: Contrast-enhanced computed tomography (CECT) is proposed as a gold standard for early evaluation of acute necrotizing pancreatitis. However, iodinated contrast media used for CECT have been shown in these circumstances to reduce pancreatic capillary flow and increase necrosis and mortality. Recent reports suggest that post-GD MRI provides images comparable to CECT in the assessment of severe acute pancreatitis. METHODS: Necrotizing pancreatitis was induced in 14 Wistar rats by intraductal glycodeoxycholic acid (10 mM/L) and intravenous caerulein (5 microg/kg/h) over 6 hours. Intravital microscopic quantitation of pancreatic capillary blood flow was performed using fluorescein isothiocyanate-labeled erythrocytes after induction of pancreatitis and 30 and 60 minutes after an intravenous bolus of either Ringer's solution or GD-DTPA (0.2 mL/kg). RESULTS: The two study groups were comparable with regard to mean arterial pressure, heart rate, arterial blood gases, hematocrit, amylase, lipase, and trypsinogen activation peptide production throughout the experiment. GD-DTPA did not reduce capillary flow (1.93 +/- 0.05 nL/capillary/min) compared to animals infused with Ringer's solution (1.90 +/- 0.06 nL/capillary/min). CONCLUSIONS: Intravenous injection of GD-DTPA does not further impair pancreatic microcirculation or increase acinar injury in acute necrotizing pancreatitis. Because of this advantage over CT contrast medium, further development of MRI as a staging tool in acute pancreatitis seems desirable.     

Ras p21 protein levels in human plasma from patients with chronic obstructive pulmonary disease (COPD) compared with lung cancer patients and healthy controls

To explore the value of an increase in ras p21 proteins in plasma as a biomarker for the carcinogenic process or for the general disease state, we have directly analysed for ras p21 proteins, plasma samples from Polish human patients with chronic obstructive pulmonary disease (COPD). They were compared with appropriate controls and also with the Polish lung cancer patients previously examined before treatment [D. Anderson, J.A. Hughes, A. Cebulska-Wasilewska, E. Nizankowska, B. Graca, Ras oncoproteins in human plasma from lung cancer patients and healthy controls, Mutat. Res. 349 (1996) 121-126]. An elevated level of ras p21 proteins was considered to be greater than 2 standard deviations (SD) above the mean negative control values. Nine out of 20 COPD patients (mean age = 65.9 years) had increased ras p21 protein levels when compared with 20 age-matched (mean age = 62.4 years) controls of the present study with a mean + 2 SD of 0.70. Eighteen out of 40 lung cancer patients (mean age = 60.1 years) had increased ras p21 protein levels compared with their concurrent controls (mean age = 40.2 years) with a mean + 2 SD of 2.53. However when compared with the age-matched controls of this present study, there were 35 out of 40 (87.5%) with increased levels. When the COPD patients and lung cancer patients were compared with 101 historical controls (age range 25-76 years, of those whose age was recorded) from unexposed healthy populations from Poland, Estonia and Spain with a mean + 2 SD of 1.83, then 4 out of 20 (20%) COPD patients and 30 out of 40 (75%) lung cancer patients had increased levels. Whether using concurrent controls, age-matched controls or historical controls, the data would suggest that an increase in ras p21 protein levels in plasma from lung cancer patients could be a possible prognostic marker or biomarker for lung cancer. COPD patients when compared with historical controls or age-matched controls had lower ras p21 protein values than cancer patients. Their ras p21 protein values might also be a biomarker for cancer. It is possible that some of these COPD patients were in the process of developing cancer or perhaps would die from COPD before cancer develops. It cannot be ruled out that the increases could be a biomarker of exposure since many of the lung cancer patients and most of the COPD patients were smokers.     

Significance of elevated IgG anticardiolipin antibody levels in patients with Budd-Chiari syndrome

OBJECT: Congenital spinal hamartomas are defined as tumors of well-differentiated mature elements situated in an abnormal location. In this report, the authors document the clinical and pathological features of spinal hamartomas in 10 patients. METHODS: Ten patients presented with midline dorsal malformations at birth, initially diagnosed as teratomas or myelomeningoceles. The locations of the masses were variable: two were located in the thoracic region, four at the thoracolumbar junction, two in the lumbar region, one at the lumbosacral junction, and one in the sacral region. The results of the neurological examination were normal in nine patients. All but one mass had intact skin and seven had palpable bone components. Neuroimaging studies revealed widening of the spinal canal, heterotopic bone located dorsally in some patients, and varying degrees of involvement of the intraspinal contents. During surgery, six patients were found to have involvement of the spinal cord or cauda equina. The pathological characteristics of the masses included three or more of the following: bone, cartilage, synovial membrane, urinary tract tissue, cyst wall, yellow or brown fat, and nerves. The well-differentiated cellular elements, which formed mature structures, along with the absence of primitive cellular components and neoplastic characteristics are more consistent with a diagnosis of hamartoma than teratoma. CONCLUSIONS: In this series, the authors describe a lesion that is overt on physical examination, yet can have occult spinal canal involvement. Complete neurosurgical evaluation is essential to provide appropriate treatment and prognosis.     

Westermark''s sign in the diagnosis of pulmonary emboli in patients with the adult respiratory distress syndrome

Two patients with adult respiratory distress syndrome (ARDS) are described in which the development of localized areas of increased lucency on chest roentgenogram, Westermark's sign, aided in the rapid diagnosis of concurrent pulmonary emboli. Recognition of this radiological sign represents a noninvasive technique for diagnosing this complication.     

High proportions of mtDNA duplications in patients with Kearns-Sayre syndrome occur in the heart

Kearns-Sayre syndrome (KSS) is a sporadic multisystem mitochondrial disorder characterized by progressive external ophthalmoplegia, pigmentary retinopathy, onset before age 20, and severe cardiac conduction defects that can lead to death. KSS patients harbor partial deletions of mitochondrial DNA (delta-mtDNA), sometimes associated with the corresponding mtDNA duplication (dup-mtDNA). As reports on the distribution of dup-mtDNAs among KSS tissues are scarce, we searched for the presence of dup-mtDNAs in different autopsy tissues of two such patients, one of whom carried the so-called "common deletion." Using a newly developed long polymerase chain reaction (PCR) protocol in conjunction with Southern blot analyses, we found dup-mtDNAs in most of the examined tissues from both patients. The proportion of dup-mtDNA in these tissues was much lower than the proportion of delta-mtDNA, with one notable exception: in both patients, we found an unusually high level of dup-mtDNA in the heart. These data suggest that dup-mtDNAs may be more stable in heart tissue of KSS patients than in other long-lived postmitotic tissues.     

High lung inflation increases mRNA levels of ECM components and growth factors in lung parenchyma

Remodeling of pulmonary capillaries occurs after chronic increases in capillary pressure (e.g., mitral stenosis). Also, remodeling of pulmonary arteries begins within 4 h of increased wall stress and is endothelium dependent. We have previously shown that high lung inflation increases wall stress in pulmonary capillaries. This study was designed to determine whether high lung inflation induces remodeling of the extracellular matrix (ECM) in lung parenchyma. Open-chest rabbits were ventilated for 4 h with 9-cmH2O positive end-expiratory pressure (PEEP) on one lung and 1-cmH2O PEEP on the other (High-PEEP group), or with 2-cmH2O PEEP on both lungs (Low-PEEP group). An additional untreated control group was also included. We found increased levels of mRNA in both lungs of High-PEEP rabbits (compared with both the Low-PEEP and untreated groups) for alpha1(III) and alpha2(IV) procollagen, fibronectin, basic fibroblast growth factor, and transforming growth factor-beta1. In contrast, alpha2(I) procollagen and vascular endothelial growth factor mRNA levels were not changed. We conclude that high lung inflation for 4 h increases mRNA levels of ECM components and growth factors in lung parenchyma.     

High levels of interleukin-12 in the aqueous humor and vitreous of patients with uveitis

OBJECTIVE: This study aimed to investigate the role of interleukin-12 (IL-12) and interleukin-10 (IL-10) in initiation and maintenance of intraocular inflammation. DESIGN: Case series. PARTICIPANTS: Aqueous humor and vitreous levels of IL-12 and IL-10 were measured in 22 patients with uveitis undergoing cataract surgery, paracentesis of the anterior chamber, and/or vitrectomy for diagnostic reasons, and in 4 patients with cataract only. INTERVENTION: Aqueous humor and vitreous levels of IL-12 and IL-10 were measured with specific enzyme-linked immunosorbent assays. MAIN OUTCOME MEASURES: Disease activity was correlated to IL-12 levels in the aqueous humor and the vitreous of patients with uveitis. RESULTS: Cytokine levels found in the anterior chamber and the vitreous are presented in picogram/milliliter (medium; range). The highest IL-12 levels were found in patients with active uveitis (108.5 pg/ml; 72-293 pg/ml). Interleukin-12 in patients with moderate uveitis or with their disease in remission was lower (32 pg/ml; 15-94 pg/ml) than in patients with active disease (P > 0.001) but higher than in the control group (10.5 pg/ml; 9-14 pg/ml). Interleukin-10 was detectable in only 3 of 22 patients with uveitis (12 pg/ml; 9-23 pg/ml). CONCLUSION: The authors found statistically significant differences of IL-12 levels in the various patient groups (active vs. inactive vs. control). These results support the idea that these uveitis cases represent type 1 (Th1)-T lymphocyte-mediated diseases in which IL-12 plays a pivotal role in the initiation and maintenance of the intraocular inflammation. The high levels of IL-12 in the vitreous and/or aqueous humor of the patients with uveitis suggest that susceptibility or resistance to ocular autoimmunity may be connected to a genetic predisposition to an elevated Th1 response.     

Elevated tear interleukin-6 levels in patients with Sj?gren syndrome

OBJECTIVE: The purpose of the study was to investigate interleukin-6 (IL-6) levels in the tear fluid and sera of patients with Sj?gren syndrome (SS). PARTICIPANTS: Twelve patients with primary SS and 12 normal control subjects participated. INTERVENTION: Tear fluid and sera were obtained from the study and the control groups. Evaluation of tear fluid and sera IL-6 levels was done by using a quantitative enzyme-linked immunosorbent assay kit. All assays were carried out blindly with respect to diagnosis. MAIN OUTCOME MEASURES: Tear fluid IL-6 levels were measured. RESULTS: The mean concentration (+/- standard error) of IL-6 in the tears of patients with SS was elevated significantly compared to that of normal control subjects (88.6+/-16.2 vs. 42.1+/-10.6 pg/ml; P < 0.05). No significant differences were noted in the serum IL-6 levels between the two groups. A significant correlation (r = 0.742, P = 0.006) was found between tear fluid IL-6 levels and the focus score of lip biopsy specimens in patients with SS. CONCLUSION: Tear fluid IL-6 levels may serve as an important marker for tear gland involvement in SS.     

A fatal case of ovarian hyperstimulation syndrome with cerebral infarction

BACKGROUND: A 76-year-old man developed allergic bronchopulmonary aspergillosis initially presenting with cough variant asthma. Symptoms worsened after exposure to ground mulch which was an identifiable source of Aspergillus fumigatus. Symptoms improved after corticosteroids and avoidance measures were instituted. OBJECTIVE: To report a case of allergic bronchopulmonary aspergillosis presenting as cough variant asthma with identifiable source of Aspergillus fumigatus. METHODS: Single case report. Serum precipitating antibodies against Aspergillus fumigatus were tested using gel diffusion techniques. Total IgE, specific IgE, and IgG indices were measured by ELISA. Cutaneous reactivity to Aspergillus fumigatus was also tested. RESULTS: Skin test and serum precipitating antibodies to Aspergillus fumigatus were positive. Precipitins were also detected between Aspergillus fumigatus and the mulch. Total serum IgE was 538 IU/mL (1290 ng/mL) which declined to 228 IU/mL (544 ng/mL) after corticosteroid therapy. IgE index = 1.10 and IgG index = 2.86. CONCLUSION: Allergic bronchopulmonary aspergillosis can present as cough variant asthma. Identification of exacerbating factors such as sources of Aspergillus fumigatus are important in management.     

Decreased cholecystokinin levels in cerebrospinal fluid of patients with adult chronic hydrocephalus syndrome

Cholecystokinin (CCK) levels were measured in cerebrospinal fluid (CSF) of patients with adult chronic hydrocephalus syndrome (ACHS) (n = 16) and compared with levels from a control group (n = 11). The CSF concentration of CCK in the ACHS group (0.79 +/- 0.53 fmol/mL) was significantly reduced (p = .002) with respect to the controls (1.55 +/- 0.54 fmol/mL). As CCK-8, the most prevalent from of CCK in the central nervous system, has been demonstrated to play a significant role in several physiological and behavioral actions, the reduced octapeptide values found in ACHS could be involved in the disturbances associated with this disorder. Continuous monitoring of intracranial pressure (ICP) demonstrated different ICP profiles in ACHS. We found that all patients with abnormal ICP records except one showed CCK values under the detection limit. Three of the 4 patients with normal ICP had CCK levels within the normal range. These preliminary studies could evidence that ICP alterations are responsible for part of the loss of brain neuropeptide levels in ACHS.