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L-selectin expression affects T-cell circulation following isoproterenol infusion in humans.

beta-Adrenergic receptor agonists have been shown to affect leukocyte migration. This study examined the expression of cellular adhesion molecules on lymphocyte, monocyte, and granulocyte distribution following an infusion of isoproterenol (20 and 40 ng/kg/min for 15 min each) in 12 healthy subjects. Leukocyte populations and adhesion molecule expression were determined via flow cytometry. Isoproterenol led to an expected lymphocytosis and leukocytosis. L-selectin expression varied across leukocytes and influenced cell trafficking in response to isoproterenol. Approximately 60% of CD8+ T-cells expressed L-selectin (CD8+CD62L+) and these cells showed no appreciable response to isoproterenol. In contrast, CD8+CD62L- cells showed a robust increase in number and distribution of approximately 100% over baseline (p's < .001). Across CD4+ T-helpers, L-selectin was expressed on approximately 86% of cells. CD4+CD62L+ cells decreased in number and distribution (p's < .001) with isoproterenol, while CD4+CD62L- cells showed a modest increase (p's < or = .05). In contrast to lymphocytes, nearly all monocytes and granulocytes expressed L-selectin; these cells increased and decreased respectively in response to isoproterenol (p's < or = .05). CD11a (the beta 2-integrin LFA-1) was expressed on > 95% of all leukocytes and these data were thus similar to the overall leukocytosis data. CD54 (ICAM-1) was expressed on approximately 60% of mixed lymphocytes and was unchanged in response to isoproterenol. The findings indicate that L-selectin expression influences T-cell trafficking in response to beta-adrenergic stimulation and help further illuminate catecholamine-mediated sympathetic and immune interactions.

Adrenergic beta-Agonists↗

Blood cytokine response of low-dose molgramostim (rhGM-CSF)-treated patients.

We examined leukocyte counts and ex vivo cytokine response of whole blood to lipopolysaccharide (LPS) or lipoteichoic acid (LTA) in patients under low-dose molgramostim therapy. Patients were injected subcutaneously daily for ten days with 1 microg/kg (n=9) or 2 microg/kg (n=14) molgramostim. Leukocytosis was observed in all patients, but only the eosinophil fraction was significantly increased in relation to other leukocyte populations. Ex vivo IFN-gamma release was decreased and IL-10 and IL-1ra secretion were increased in response to LPS or LTA. Thus, in non-neutropenic patients, leukocytosis can already be initiated by low doses of molgramostim. The ex vivo cytokine data suggest that these doses prime blood towards a systemic anti-inflammatory response.

Adult↗

Brain IL-1beta increases neutrophil and decreases lymphocyte counts through stimulation of neuroimmune pathways.

Leukocytosis after cerebral injury is well described and may participate in the generation of cerebral damage. However, the mechanisms of brain-induced leukocytosis are still speculative. Since it is known that proinflammatory cytokines are involved in neuroimmunomodulation and since others and we have demonstrated high cytokine levels in the cerebrospinal fluid following injury, we supposed that brain cytokines may also influence leukocyte counts. In order to evaluate this hypothesis, we established an animal model using continuous intracerebroventricular (i.c.v.), intrahypothalamic (i.h.), or intravenous infusion of the proinflammatory cytokines tumor necrosis factor (TNF)-alpha and IL-1beta. Controls received vehicle solution. With this experimental paradigm we could show that i.c.v. and i.h. infusion of IL-1beta but not TNF-alpha dramatically increased neutrophil counts, whereas lymphocytes dropped. Blocking the hypothalamic-pituitary-adrenal (HPA) axis by hypophysectomy abolished the neutrophilia, whereas the lymphopenia remained unchanged. Furthermore, application of the beta2-adrenoreceptor antagonist propranolol prevented the decrease of lymphocytes and diminished the neutrophilia. All parameters normalized within 48 h after termination of infusion. So, our results demonstrate that brain IL-1beta can modify blood leukocyte counts through stimulation of both the sympathetic nervous system (SNS) and the HPA axis.

Adrenergic beta-2 Receptor Antagonists↗

Cytokine and lymphocyte activation during experimental acute pyelonephritis.

We studied the cellular and humoral events which follow experimental acute pyelonephritis from P-fimbriated Escherichia coli to gain insight into the relationships among cells and specifically cytokines to determine how early events in untreated infection lead to renal damage. Cynomolgus (Macaca fascicularis) monkeys were studied after they were subjected to unilateral ureteral bacterial inoculation. We evaluated the blood for leukocytosis and studied lymphocyte subsets using flow cytometry and monoclonal antibodies to the subsets and serum, complement, cytokines and antibody titers. Interleukin-1, 2 and 6 and tumor necrosis factor (TNF) were assayed by enzyme-linked immunoadsorbent assay (ELISA), using monoclonal and polyclonal antibodies. Leukocytosis was marked and there were significant elevations in serum cytokines, interleukin-1 alpha, 2 and 6 with only small changes in the level of TNF. Interleukin-2 levels were sustained and may have upregulated the homing receptor for virgin lymphocytes. The studies illustrated the unique relationship between cytokines and lymphocytes and the response to bacterial infection, showing that the inflammatory response is regulated not only by cytokine activity but also by lymphocyte activation.

Acute Disease↗

An unusual case of chronic myelocytic leukemia characterized by a conspicuous tissue infiltration treated with leukapheresis.

An unusual case of chronic myelocytic leukemia (CML) is described that presented leukocytosis at onset (720 X 10(9)/l), symptoms of stasis, organomegaly, and a conspicuous infiltration of leukemic cells from the pelvis to the right popliteal cavity. As initial therapy and in addition to chemotherapy, six therapeutic leukapheresis treatments (TL) were performed and the patient showed dramatic symptomatic improvement with reduction in leukocytosis (97 X 10(9)/l), organomegaly, and tissue infiltration.

Adult↗

Acid-induced esophagitis in cats is prevented by sucralfate but not synthetic prostaglandin E.

The cytoprotective effects of liquid sucralfate and a synthetic analog of prostaglandin E1 (PGE1) on acid-induced esophagitis in cats were studied. Esophagitis was induced in adult cats using a constant infusion of 0.1 N HCl at 1 ml/min for 20 min. Animals were infused for either one or three days. Mucosal lesions were evaluated by blinded investigators using both fiberoptic endoscopy and light microscopy. Histologic changes included basal cell hyperplasia, intraepithelial leukocytosis, and subepithelial leukocytosis. Liquid sucralfate given prior to acid infusion consistently prevented acid-induced lesions in both one- and three-day infusions, demonstrated by both endoscopy and quantitative histologic scoring. Indomethacin (200 micrograms/kg) given prior to sucralfate and acid did not affect sucralfate cytoprotection. Synthetic PGE1, given in doses of 5 micrograms/kg and 100 micrograms/kg, afforded no esophageal cytoprotection. These studies indicate that sucralfate is cytoprotective against acid-induced esophageal injury in cats, an effect that does not appear to be mediated by prostaglandin. In addition, synthetic PGE1 does not confer protection in this animal model.

Animals↗

Pyogenic liver abscess: multivariate analysis of risk factors.

Seventy-three patients with pyogenic liver abscess during the year 1978-1988 were studied in the Kaohsiung Medical College Hospital. The overall mortality rate was 19.2% in this study. By using univariate analysis, it was revealed that clinical jaundice, pleural effusion, bilobar abscess, profound hypoalbuminemia (less than 2.5 g/dl), hyperbilirubinemia (less than 2 mg/dl), elevated level of serum AST (greater than 100 IU/L), alkaline phosphatase (greater than 150 IU/L), and marked leukocytosis (greater than 20,000 mm3) were associated with a higher mortality rate. Multivariate stepwise logistic regression analysis detected only 3 factors of marked leukocytosis (greater than 20,000 mm3), profound hypoalbuminemia (less than 2.5 g/dl), and presence of pleural effusion with independent significance in predicting mortality. Meanwhile, it was also revealed that the laboratory data could not predict a risk factor to mortality unless they became markedly abnormal.

Adult↗

Cellular and morphological changes in lymphoid organs after a single injection of interleukin 1 alpha in the mouse.

We investigated the effects of a single i.v. injection of recombinant human interleukin 1 alpha (IL-1 alpha) on the morphology and the cellularity of several lymphoid organs in normal mice. The injection of 100 U of IL-1 alpha resulted in maximal neutrophilia and leukocytosis at 1 h. By 72 h, the numbers of mononuclears, but not that of polymorphonuclears, returned to baseline levels. Absolute increase in mononuclears was paralleled by relative lymphopenia. Changes in the peripheral blood coincided with rapid decrease in the spleen cellularity and white pulp volume (especially the marginal zone), and an increase in the red pulp volume. Bone marrow cellularity was increased at 1 h, but returned to control levels by 6 h after IL-1 injection. Thymus cell depletion and cortex atrophy were maximal at 6 h and could be observed throughout the experiment. These findings indicate that leukocytosis induced by a single i.v. injection of IL-1 alpha in normal mice is concomitant with a rapid cell depletion of the spleen and thymus. Morphological and cellular changes in lymphoid organs may represent the mobilization of immunocompetent cells during the development of the inflammatory response.

Animals↗

Effect of BW B70C, a novel inhibitor of arachidonic acid 5-lipoxygenase, on allergen-induced bronchoconstriction and late-phase lung eosinophil accumulation in sensitised guinea-pigs.

The actions of BW B70C, an orally available, biologically persistent and selective inhibitor of arachidonic acid 5-lipoxygenase, have been examined in two systems of anaphylaxis in actively sensitised guinea-pigs in vivo. In anaesthetised, artificially ventilated animals pretreated with mepyramine and indomethacin to leave only the "peptidoleukotriene-dependent" component (leukotrienes C4, D4 and E4) of the anaphylactic response, direct inhalation of nebulised allergen resulted in a slowly developing bronchoconstriction which was prevented in a dose-dependent manner by BW B70C (2-50 mg/kg p.o.) administered 1 or 6 h before challenge. In conscious animals fasted overnight and then pretreated with mepyramine to prevent death due to acute bronchial anaphylaxis, exposure to nebulised allergen produced slight respiratory symptoms. When blood and lung samples were analysed 4-48 h after allergen provocation a sustained leukocytosis and pulmonary eosinophil accumulation were observed. In contrast, in food-replete conscious animals, the early respiratory symptoms were still observed upon allergen inhalation, but no significant blood leukocytosis or accumulation of eosinophils in the lungs occurred subsequently. The eosinophil influx induced by allergen in fasted animals was assessed both by histological examination and determination of tissue peroxidase content, two measures which demonstrated reasonable agreement. Administration of a single dose of BW B70C (10 mg/kg p.o.) 1 h prior to allergen challenge did not affect the subsequent eosinophil infiltration 24 h later, but 20 mg/kg given in divided doses (-1 and +12 h) produced 67% inhibition of cell accumulation. A single dose of 50 mg/kg (-1 h) had a similar effect (78% inhibition). The potent glucocorticosteroid betamethasone was used as a reference compound, and 4 mg/kg given as a divided dose (-1 and +7) fully inhibited lung inflammation assessed 24 h after provocation with allergen. BW B70C inhibited both acute and allergic bronchoconstriction and late-phase eosinophil accumulation subsequent to allergen inhalation in guinea-pigs. In view of the apparent requirement for sustained plasma levels of BW B70C in order to prevent late-phase eosinophil recruitment to the lung after a single challenge with allergen, it is unclear whether inhibition of 5-lipoxygenase underlies the observed anti-eosinophil accumulation effects of the compound, but the anti-bronchoconstrictor effects are consistent with the known inhibitory activity of BW B70C against 5-lipoxygenase.

Administration, Oral↗

Granulocyte-colony stimulating factor produced by pancreatic carcinoma.

CONCLUSION: A rare case of granulocyte-colony stimulating factor (G-CSF) produced by carcinoma of the pancreas has been reported. BACKGROUND: This is the first case showing high G-CSF concentration in the aspirated tumor fluid (mucin) at its early stage without leukocytosis. METHODS: The tumor, detected incidentally in a 64-yr-old male, was removed by a distal pancreatectomy. The mass was 7.0 x 6.5 x 4.5 cm, and was histologically diagnosed as cystadenocarcinoma with prominent sarcomatous transformation. It was classified as anaplastic carcinoma. RESULTS: After 4 wk of resection, progressive leukocytosis was observed. Seven weeks after the operations, the peripheral leukocyte count increased to 126,000/mL. After 8 wk of resection, the patient died of recurrence. The serum G-CSF concentration was elevated after recurrence. The preserved mucin contained in the cystic components of the resected specimen had a G-CSF concentration higher than 2400 pg/mL. G-CSF is a known cytokine and an etiologic agent in paraneoplastic syndromes. An early diagnosis can, therefore, be made prior to the manifestation of clinical symptoms by the evaluation of the aspirated tumor fluid. This can lead to the prevention of the paraneoplastic syndrome with inhibitory cytokines in future.

Cystadenocarcinoma↗

Functional evaluations for pulmonary resection for lung cancer in octogenarians. Investigation from postoperative complications.

We have reviewed the records of our twenty-four patients aged 80 years or older who underwent lung resections for bronchogenic carcinoma between 1983 and 1997 in our department. Eighteen patients were male and six were female. Adenocarcinoma was the histology in more than half of the cases (13 patients), along with 8 squamous cell carcinoma, 2 large cell carcinoma, and one small cell lung carcinoma. More than single lobectomy was performed in each patient. Unilateral pulmonary occlusion tests were employed in patients with impairment in pulmonary functions. Every patient, who underwent the unilateral pulmonary occlusion test, was certified that the total pulmonary vascular resistance index during unilateral pulmonary arterial occlusion test was less than 700 dyne.sec.cm-5.m2. Postoperative cardiovascular complications, such as paroxysmal atrial tachycardia, premature atrial contraction, premature ventricular contraction or atrial fibrillation, were seen in 10 patients. Postoperative respiratory complications, namely, sputa retention, retained secretions or atelectasis, were seen in 7 patients. The extent of dissection of mediastinal lymph node was not correlated to the postoperative pulmonary complications. However, the incidence of arrhythmias in the patients who received R2 mediastinal lymphnode dissection was much higher than in those who received R1 or R0 dissection. Complete blood counts and serum biochemical analysis performed at about three weeks after operations revealed leukocytosis and increases in levels of serum transaminase. These phenomena in leukocytosis and increases in the levels of serum transaminase in these patients were similar to those in younger patients. There was no operative death. We conclude that some patients over 80 years are candidates for lung resection after careful preoperative cardiopulmonary evaluation.

Adenocarcinoma↗

Routine clinical laboratory tests correspond to increased serum levels of 3-hydroxy fatty acids, markers of endotoxins, in cardiosurgery patients.

INTRODUCTION: Endotoxemia developing during cardiosurgery as elevated endotoxin concentrations in patient's serum may prevail over 24 h after operation. A major reason is thought to be increased gut permeability resulting in endotoxin and bacterial leakage. In this study we aimed to measure endotoxin levels on samples obtained during and after cardiovascular procedures and compare them with clinical observations and laboratory test results. MATERIALS AND METHODS: 3-Hydroxy fatty acids (3-OH FAs) of 10-18 carbon chain length, chemical markers of endotoxin (lipopolysaccharide), were determined in patient sera by gas chromatography-mass spectrometry-based analysis. RESULTS were compared with routine laboratory tests: blood morphology, urine, ALT, AST, bilirubin, kidney parameters, clotting parameters, and gasometry. RESULTS: Of a total of 16 patients, 5 patients (group I) showed increased serum 3-OH FA levels and 11 patients (group II) did not show any change in 3-OH FA levels 24 h after operation. All group I patients revealed leukocytosis, two developed post-operative anemia. Significantly different changes were observed: the initial, pre-operative 3-OH FA levels were similar for both groups, while group I patients showed increased levels of all the studied 3-OH FAs during the operation (p</=0.05), and 3-OH C14 and 3-OH C16 remained elevated 24 h after the operation. CONCLUSIONS: Cardiosurgery may strongly promote gut endotoxin translocation to the blood in some patients. Prolonged leukocytosis, deep anemia, and increased liver dysfunction markers may indicate the need for observation of possible endotoxemia development. It is recommended to monitor the endotoxin level and/or endotoxemia markers in cardiosurgery patients.

Biomarkers↗

Cardiac inflammatory pseudotumor: rapid appearance in an infant with congenital heart disease.

The rapid growth of an inflammatory pseudotumor in the right atrium of an infant with pulmonary valve stenosis and atrial septal defect is documented. Systemic manifestations, including fever, weight loss, leukocytosis, and hypergammaglobulinemia, suggested infection; the diagnosis was made after surgical resection. Sixteen months after surgery the infant is asymptomatic, and the hypergammaglobulinemia and leukocytosis have resolved. Trauma may have been the inciting factor for this inflammatory pseudotumor.

Echocardiography↗

Factors associated with clinically significant anastomotic leakage after large bowel resection: multivariate analysis of 707 patients.

The aim of this study was to determine by univariate and multivariate analyses the factors associated with clinically significant anastomotic leakage (AL) after large bowel resection. From 1990 to 1997 a series of 707 patients underwent colonic or rectal resection (without a stoma). Patients were divided into two groups: those with clinical anastomotic leakage (group 1) and those without it (group 2). AL occurred in 43 of 707 patients (6%). The overall mortality was 2.2% and was significantly higher in patients with AL than in those without: 5 of 43 (12%) versus 11 of 664 (1.6%), p < 0.001. Univariate analysis showed 15 variables associated with the risk of AL: previous abdominal or pelvic irradiation (p = 0.02), American Society of Anesthesiologists (ASA) score > 2 (p = 0.04), leukocytosis (p = 0.02), renal failure (p = 0.03), steroid treatment (p = 0.01), duration of operation (p = 0.001), intraoperative septic conditions (p = 0.006), total colectomy (p = 0.009), transverse colectomy (p = 0.02), difficulties encountered during anastomosis (p = 0.001), ileorectal anastomosis (p = 0.02), colocolic anastomosis (p = 0.01), abdominal drainage (p = 0.05), and blood transfusion intraoperatively (p = 0.006) and postoperatively (p = 0.001). Multivariate analysis showed that only preoperative leukocytosis (p = 0.04), intraoperative septic conditions (p = 0.001), difficulties encountered during anastomosis (p = 0.007), colocolic anastomosis (p = 0.004), and postoperative blood transfusion (p = 0.0007) were independent factors associated with AL. The risk of AL increased from a range of 12% to 30% if one risk factor was present, to 38% with two factors, to 50% with three factors. After colorectal resection and intraperitoneal anastomosis, a temporary protective stoma is proposed in selected patients with high risk factors for AL, as observed in our study.

Adolescent↗

Usefulness of known computed tomography and clinical criteria for diagnosing strangulation in small-bowel obstruction: analysis of true and false interpretation groups in computed tomography.

Computed tomography (CT) criteria have proven useful, but not sufficient, for diagnosis of bowel strangulation. The purpose of the present study was to evaluate the use of clinical criteria in the interpretation of CT scans as a means of improving the diagnostic accuracy of CT, especially in patients whose CT scans are equivocal for distinguishing simple obstruction from strangulated obstruction. We analyzed the CT scans of 136 patients with simple (n=70) or strangulated (n=66) small-bowel obstruction. Three radiologists interpreted the CT scans independently for the presence of intestinal strangulation. According to their interpretation, 136 patients were divided into two groups, i.e., a false and a true interpretation group. The diagnostic value of known CT and four clinical criteria (tenderness, tachycardia, fever, and leukocytosis) were compared in the two groups. The diagnostic accuracy of CT criteria for distinguishing simple obstructions from strangulated small-bowel obstructions ranged between 73% and 80%. Of the 136 patients, 31 belonged to the false group and 105 to the true group. The CT criteria that were highly specific in both groups included severe mesenteric haziness, serrated beak, and poor bowel wall enhancement. Among the clinical criteria, both tachycardia and leukocytosis were highly specific in both groups. The number of positive clinical criteria was helpful in making a diagnosis; none or one clinical criterion indicated a simple obstruction, whereas three or four criteria indicated a strangulated obstruction; when this result was applied retrospectively to the false group, the CT diagnostic accuracy improved in 19 of the 31 patients. The use of clinical criteria when CT findings are equivocal, may overcome the inherent limitations of CT for diagnosing strangulated small-bowel obstruction.

False Negative Reactions↗

Clinical data and factors associated with poor outcome in pneumococcal meningitis.

We carried out a 4-year study of 159 children (ages 1 month-14 years) with pneumococcal meningitis. The study was divided into two periods: the retrospective period (1998-2000: 107 patients), and the prospective period (2001-2002: 52 patients). About 2/3 of the children were under 2 years of age: 72 (45%) were under 1 year of age and 38 (24%) had meningitis during the second year of life. One-third of the patients had signs of otitis media; convulsions were more frequent in patients under 1 year compared with older patients (34.7 vs. 14.9%; P=0.004); 13/159 children (8.2%) died; 93/159 (58.5%) recovered completely, 12.6% had motor sequelae, 6.9% hydrocephalus, 29.8% sensorineural hearing loss; 140/159 (88%) were treated with third generation cephalosporins, yet only 8.7% of the pneumococci identified were completely penicillin-resistant (> or =1 microg/ml); 119/159 were treated with dexamethasone. Four patients had received an injection of heptavalent vaccine. Antibiotics for 1 week prior to admission, shock, abnormal pupils, leukocytes count <6,000 mm(3), and CSF glucose < or =8.5 mg/dl were significantly associated with poor outcome and/or death in the univariate analysis. No patient with leukocytosis >16,000/mm(3) died. Conclusion. Sequelae are very common in pneumococcal meningitis. Poor outcome was associated with pupillary abnormality and a leukocyte count <6,000/mm(3) on admission. Leukocytosis was protective against poor outcome.

Anisocoria↗

Expression of Bcl-2 on leukocytes in prostatic fluid from patients with acute and chronic prostatitis.

In our continuing investigation to clarify the significance of leukocytosis and its prolongation in prostatic fluid (PF) from prostatitis patients, we investigated whether expression of the antiapoptotic gene Bcl-2 on leukocytes in prostatic fluid has any relation with prolonged leukocytosis in prostatitis. The subjects were eight patients with acute bacterial prostatitis (ABP) and eight with nonbacterial prostatitis (NBP) with a history of more than 2 years. Twelve micrograms of protein obtained from leukocytes in PF were subjected to Western blot analysis. Bcl-2 was expressed in seven of eight (87.5%) and six of eight (75.0%) patients with NBP and ABP, respectively. Quantitative density analysis of the Bcl-2 band did not show any statistically significant differences between patients with NBP and those with ABP. These results suggest that the expression of antiapoptotic Bcl-2 on leukocytes in PF is not a cause of leukocyte longevity in long-term prostatitis.

Acute Disease↗

Eosinophilia and endomyocardial fibrosis.

A 12 year old boy died after a 3 year course of recurrent and progressive heart failure. His cardiac symptoms began with a marked leukocytosis (white blood cell count 188,500/mm3) due to eosinophilia (90 percent). In 6 months, the leukocytosis and eosinophilia subsided, but the patient's heart failure progressed over the next 2 1/2 years. At autopsy there was no evidence of leukemia, but a severe endocardial fibrosis extending into the myocardium was found. The origin of endomyocardial fibrosis, although unknown, appears to have been related to the eosinophilia in this patient.

Child↗