Production of tumor necrosis factor alpha and interleukin-6 by alveolar macrophages from patients with rheumatoid arthritis and interstitial pulmonary disease

The aim of this study was to measure the production of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) by alveolar macrophages in patients with rheumatoid arthritis and interstitial lung disease (ILD). Rheumatoid arthritis patients diagnosed by ACR criteria (n = 8) with associated ILD documented by pulmonary function tests and high resolution computerized tomography scanning, and 12 healthy volunteers (6 smokers and 6 nonsmokers). We determined the spontaneous and induced production of bacterial lipopolysaccharides (LSP), TNF-alpha and IL-6 by alveolar macrophages obtained by bronchoalveolar lavage. The macrophages were isolated by Ficoll-Hypaque gradient centrifugation and plastic adherence and cultured in serum-containing medium (low endotoxin) in the presence and absence of LPS (100 ng/ml). TNF-alpha and IL-6 levels contents were determined in supernatants by ELISA. In the patient group both spontaneous and induced production of TNF-alpha were significantly higher than in controls (p < 0.01). Macrophages stimulated with LPS in patients with rheumatoid arthritis and ILD also released greater amounts of IL-6 than did those of the healthy controls. IL-6 spontaneous and induced production was significantly lower in smokers than in nonsmokers. TNF-alpha and IL-6 production in patients with rheumatoid arthritis and ILD, studied in bronchoalveolar lavage specimens reveals that alveolar macrophages are hyperreactive in these patients, who are possibly sensitized as a consequence of the inflammatory lung process inherent to the disease. Further study is needed to define the pathogenic role of these mediators.     

Keratosis follicularis spinulosa decalvans: confirmation of linkage to Xp22.13-p22.2

The authors report a case of presumed idiopathic chronic iridocyclitis in which an intraocular foreign body (IOFB) was finally identified. There was no history of prior eye trauma. Ophthalmologic and laboratory evaluations were inconclusive. Seven months following unsuccessful medical treatment of the iritis and given the patient's occupational history, a skull x-ray was performed followed by computed tomography of the orbits. A metallic IOFB was identified in the pars plicata and was surgically removed with resolution of the inflammation. The possibility of an IOFB should always be entertained in idiopathic iridocyclitis refractory to medical treatment, even when there is no history of ocular trauma.     

Integration of health care economics for addiction treatment in clinic care

Visceral pain is a substantial, clinical problem but unfortunately few experimental models are available to study this phenomenon in man. In the present study we inserted a stimulation catheter 5-10 cm into the ileo-sigmoidostomy of nine patients. The catheter contained six small, flexible electrodes separated by 4 mm. The gut was stimulated by single burst, repeated burst (five stimuli delivered at 2 Hz), or continuous burst stimuli (4 Hz for 30, 60, 90, and 120 s). The sensation (ST), pain detection (PDT), and pain tolerance (PTT) thresholds to single/repeated burst stimuli were determined. The location/size/sensitivity of referred pain after repeated/continuous stimulation were characterized. The brain potentials to single burst stimuli and to increasing stimulus intensity were measured. ST to single burst stimuli was easy to determine (8 mA) and to reproduce. The patients found it difficult to determine the PDT and PTT to single burst stimuli, however both thresholds were easily determined for repeated burst stimuli. The pain thresholds to single burst stimuli were twice as high as the thresholds to repeated burst stimuli, indicating the importance of central temporal summation for visceral pain. Minor changes in the stimulus location resulted in changes of the referred pain projection site. The words most frequently selected (78%) from the McGill Pain Questionnaire to describe repeated burst stimulations were shooting, pricking, flashing, and boring. The amplitude of the brain potentials increased at increasing stimulus intensity. A stimulus intensity giving an initial pain rating of around 5 on a 0-10 visual analog scale (VAS) was used for continuous stimulation. A general increase of the pain intensity and the area of referred pain was found during this stimulation. It was concluded that electrical stimulation of the human gut provokes pain and especially long sequences of visceral stimuli are adequate to evoke referred pain mimicking pain profiles of pathologic origin.     

Patellar enthesopathy in childhood: a new clinical and radiographic observation

Enthesitis occurs commonly in patients with seronegative spondyloarthropathies. The patella is frequently affected by enthesopathy, but overgrowth has not been reported as a manifestation of enthesitis in pediatrics. We describe 3 patients with seronegative enthesopathy and arthropathy syndrome and patellar overgrowth.     

The hypertension of autonomic failure and its treatment

We studied the incidence and severity of supine hypertension in 117 patients with severe primary autonomic failure presenting to a referral center over a 9-year period. Patients were uniformly characterized by disabling orthostatic hypotension, lack of compensatory heart rate increase, abnormal autonomic function tests, and unresponsive plasma norepinephrine. Fifty-four patients had isolated autonomic impairment (pure autonomic failure). Sixty-three patients had central nervous system involvement in addition to autonomic impairment (multiple-system atrophy). Patients were studied off medications, in a metabolic ward, and on a controlled diet containing 150 mEq of sodium. Fifty-six percent of patients had supine diastolic blood pressure > or =90 mm Hg. The prevalence of hypertension was slightly greater in females (63%) than in males (52%). Potential mechanisms responsible for this hypertension were investigated. No correlation was found between blood volume and blood pressure. Similarly, plasma norepinephrine (92+/-15 pg/mL) and plasma renin activity (0.3+/-0.05 ng/mL per hour) were very low in the subset of patients with pure autonomic failure and supine hypertension (mean systolic/diastolic pressure, 177 +/- 6/108 +/- 2 mm Hg, range 167/97 to 219/121). Supine hypertension represents a challenge in the treatment of orthostatic hypotension. We found these patients to be particularly responsive to the hypotensive effects of transdermal nitroglycerin. Doses ranging from 0.025 to 0.1 mg/h decreased systolic blood pressure by 36+/-7 mm Hg and may effectively treat supine hypertension overnight, but the dose should be individualized and used with caution.     

A stercoraceous ulcer of the colon in neglected Hirschsprung''s disease

Growth hormone receptor (GHR) has a major role in the regulation of growth hormone action, and thus, is an obvious candidate gene associated with milk production traits in mammals. The present authors have sequenced 273 bp of the 3' flanking region of the bovine GHR, and found three length variants and one base substitution polymorphism in this region. Allele frequencies of the length variants differ between Finnish native and commercial dairy cattle breeds. The chromosomal localization of GHR was confirmed to bovine chromosome 20 by synteny mapping and linkage analysis.     

Quantification of traumatic hemomediastinum using transesophageal echocardiography: impact on patient management

STUDY OBJECTIVES: To determine whether the quantitative evaluation of hemomediastinum using transesophageal echocardiography (TEE) is predictive of the presence of a traumatic disruption of the thoracic aorta (TDA) or its branches in patients who have sustained severe blunt chest trauma. DESIGN: Retrospective study. SETTING: ICU of a tertiary referral teaching hospital. PATIENTS: Forty-one patients sustaining severe blunt chest trauma (32 men, nine women; mean age, 43+/-16 years; mean Injury Severity Score, 39+/-22) who underwent a TEE study were divided into two groups, patients with (group TDA+, n=15) or without (group TDA-, n=26) major vascular injury diagnosed using an alternative method such as aortography, surgery, or necropsy. The control group included 41 age- and sex-matched patients with an unremarkable TEE study performed to rule out an intracardiac source of emboli. INTERVENTIONS: The presence of hemomediastinum was quantitatively assessed by measuring the distances between the esophageal scope and anteromedial aortic wall (distance 1), and between the posterolateral aortic wall and left visceral pleura (distance 2) at the level of the aortic isthmus. An observer who was unaware of both medical history and final diagnosis measured the distances. MEASUREMENTS AND RESULTS: In group TDA+, TEE demonstrated aortic injuries in 13 patients, revealed an isolated hemomediastinum in one patient (ruptured intercostal arteries), and was unremarkable in the remaining patient, who sustained a disrupted right subclavian artery. No associated major vessel injuries were diagnosed in the group TDA- (normal aortograms). When compared to the control group, mean distances were greater in patients with chest trauma (distance 1=5.5+/-4.4 mm vs 2.7+/-0.8 mm, p=0.001; distance 2=3.8+/-5.0 mm vs 1.2+/-0.3 mm, p=0.02). The corresponding distances were even greater in group TDA+ when compared with group TDA- (distance 1=8.6+/-5.9 mm vs 3.7+/-1.5 mm, and distance 2=7.1+/-7.0 mm vs 2.0+/-1.7; for both differences, p<0.01). A threshold value of 5.5 mm for distance 1 or 6.6 mm for distance 2 had a sensitivity of 80%, a specificity of 92%, a positive and negative predictive value of 86% and 89%, respectively, for the diagnosis of underlying major vascular injury. CONCLUSIONS: TEE allows quantitative assessment of traumatic hemomediastinum. The presence of a large hemomediastinum requires further evaluation by aortography, even if the thoracic aorta appears normal during the TEE examination, in order to rule out an underlying major vascular injury which may be outside the field of view of the echocardiographer.     

The Pseudomonas aeruginosa rhlG gene encodes an NADPH-dependent beta-ketoacyl reductase which is specifically involved in rhamnolipid synthesis

A Pseudomonas aeruginosa gene homologous to the fabG gene, which encodes the NADPH-dependent beta-ketoacyl-acyl carrier protein (ACP) reductase required for fatty acid synthesis, was identified. The insertional mutation of this fabG homolog (herein called rhlG) produced no apparent effect on the growth rate and total lipid content of P. aeruginosa cells, but the production of rhamnolipids was completely abrogated. These results suggest that the synthetic pathway for the fatty acid moiety of rhamnolipids is separate from the general fatty acid synthetic pathway, starting with a specific ketoacyl reduction step catalyzed by the RhlG protein. In addition, the synthesis of poly-beta-hydroxyalkanoate (PHA) is delayed in this mutant, suggesting that RhlG participates in PHA synthesis, although it is not the only reductase involved in this pathway. Traits regulated by the quorum-sensing response, other than rhamnolipid production, including production of proteases, pyocyanine, and the autoinducer butanoyl-homoserine lactone (PAI-2), were not affected by the rhlG mutation. We conclude that the P. aeruginosa rhlG gene encodes an NADPH-dependent beta-ketoacyl reductase absolutely required for the synthesis of the beta-hydroxy acid moiety of rhamnolipids and that it has a minor role in PHA production. Expression of rhlG mRNA under different culture conditions is consistent with this conclusion.     

Renal masses simulating primary renal cell carcinoma in patients with advanced malignancies

Most patients who present with a large solid renal mass and evidence of advanced malignancy will have primary renal cell carcinoma but a small subset with similar features have different and more treatable malignancies. We identified 7 patients with clinical and radiological findings suggestive of metastatic renal cell carcinoma who were ultimately diagnosed as have non-Hodgkin's lymphoma (5), germ cell tumor (1) or transitional cell carcinoma (1). Two of these patients presented with abdominal pain, gross hematuria and a flank mass. Computerized tomography was interpreted as showing renal cell carcinoma in all patients, although lymphoma and sarcoma were included in the differential diagnoses in 2. With the correct diagnosis and appropriate therapy, 4 of the 7 patients are currently disease-free. We emphasize the need for histological documentation in such patients in view of curative therapy available for possible underlying neoplasms simulating renal cell carcinoma.