Highly purified murine interleukin 5 (IL-5) stimulates eosinophil function and prolongs in vitro survival. IL-5 as an eosinophil chemotactic factor.

The recent molecular cloning of the complementary DNA encoding T cell--replacing factor (TRF) has demonstrated that a single molecule is responsible for B cell growth factor II (BCGF-II) activity and eosinophil differentiation activity. It has been proposed that this molecule be called interleukin 5 (IL-5). We previously reported that purified rIL-5 supports the terminal differentiation and proliferation of eosinophilic precursors. In this study, we examined the effects of IL-5 on functional activities of mature eosinophils. IL-5 maintained the viability of mature eosinophils obtained from peritoneal exudate cells of mice infected with parasites. It also induced superoxide anion production in a dose-dependent manner. The Boyden's chamber Millipore assay revealed that IL-5 had a marked chemokinetic effect on eosinophils in a dose-dependent manner. Moreover, IL-5 was found to be an eosinophil chemotactic factor by the checkerboard assay. In conclusion, IL-5 is suggested to play an important role in increasing the functional activities of eosinophils as well as their production in allergic and parasitic diseases.

Diabetic peripheral neuropathy and prevalence of erectile dysfunction in Japanese patients aged <65 years with type 2 diabetes mellitus: The Dogo Study.

Only limited epidemiological evidence exists regarding the relationship between diabetic neuropathy and erectile dysfunction (ED) among Japanese patients with type 2 diabetes mellitus. To investigate the relationship between diabetic neuropathy and ED among Japanese patients with type 2 diabetes mellitus, a multicenter cross-sectional study was conducted in 287 male Japanese patients with type 2 diabetes mellitus, age (19-65 years). Diabetic neuropathy was diagnosed if the patients showed two or more of the following three characteristics: neuropathic symptoms, decreased or disappeared Achilles tendon reflex and/or abnormal vibration perception. ED, moderate to severe ED, and severe ED were defined as present when a subject had a Sexual Health Inventory for Men score <22, <12 and <8, respectively. The prevalence values of diabetic neuropathy and severe ED were 47.0 and 39.0%, respectively. Diabetic neuropathy was independently positively associated with severe ED, but not ED and moderate ED: the adjusted odds ratio was 1.90 (95% confidence interval: 1.08-3.38). No relationships were found between diabetic retinopathy or diabetic nephropathy and ED. Diabetic neuropathy is positively associated with severe erectile dysfunction among Japanese type 2 diabetes mellitus patients aged <65 years.

Depressive symptoms and prevalence of erectile dysfunction in Japanese patients with type 2 diabetes mellitus: the Dogo Study.

In several studies of patients with type 2 diabetes mellitus, a positive association between depressive symptoms and erectile dysfunction (ED) has been reported. No evidence exists, however, regarding the association between depressive symptoms and ED among Japanese patients with type 2 diabetes mellitus. Thus, we examined this issue among Japanese patients with type 2 diabetes mellitus. Study subjects were 469 male Japanese patients with type 2 diabetes mellitus, aged 19 years or over. ED, moderate to severe ED and severe ED were defined as present when a subject had a Sexual Health Inventory for Men score <22, <12 and <8, respectively. Depressive symptoms were defined as present when a subject had a Self-Rating Depression Scale (SDS) score >49. Adjustment was made for age, body mass index, waist, duration of type 2 diabetes, current smoking, current drinking, hypertension, dyslipidemia, coronary artery disease, stroke, glycated hemoglobin and diabetic neuropathy. The prevalence values of depressive symptoms, moderate to severe ED and severe ED were 15.1%, 64.2% and 51.0%, respectively. Depressive symptoms were independently positively associated with moderate to severe ED and severe ED (adjusted odds ratios were 2.23 (95% confidence interval (CI): 1.17-4.43) and 1.86 (95% CI: 1.04-3.41), respectively). In Japanese patients with type 2 diabetes mellitus, depressive symptoms may be associated with ED.

Characterization of neutrophil activation by repeated injection of endotoxin in rabbits. Role of neutrophils in the generalized Shwartzman reaction.

The relationship between activated neutrophils and end-organ injury in endotoxemia was studied. The function of peripheral blood neutrophils (PMNs) in rabbits with the generalized Shwartzman reaction (GSR) was compared to that of PMNs rabbits receiving a single injection of endotoxin. The following results were obtained: (1) PMNs from rabbits with the GSR demonstrated enhanced adherence to endothelial cells and increased mitochondrial ATP production; (2) the GSR did not enhance chemotaxis and oxygen radical production of PMNs; (3) a single injection of endotoxin did not cause necrosis of visceral organs; (4) in vitro detachment of endothelial cells by PMNs was increased in rabbits with the GSR; (5) in vivo administration of monoclonal antibody (mAb) against CD11b/CD18 (Mac-1) suppressed the increase in PMN adherence; and (6) hemorrhagic necrosis did not occur when mAb to Mac-1 was injected. Thus, enhanced adherence of PMNs to endothelial cells appears to play a key role in endotoxin-induced end-organ injuries in this animal model.

Characteristics of alveolar macrophages in experimental septic lung.

We investigated the pathogenesis of lung injury in sepsis (septic adult respiratory distress syndrome) by focusing on the functional changes of alveolar macrophages (AMs). Sepsis was induced in male WK rats by cecal ligation and puncture. Histological examination of the lungs from this experimental model revealed edematous change at 24 h after the surgery. The protein and endotoxin concentrations in the bronchoalveolar lavage fluid (BALF) increased with time after the surgery. The time course studies of AM function after surgery indicated that AMs from septic rats were activated by endotoxins. Specifically, this was suggested by the finding that AM adherence to and spreading on a plastic dish had increased. On stimulation, these AMs enhanced generation of superoxide anions and increased release of lysosomal enzymes, such as beta-glucuronidase. On the other hand, AMs in sepsis generated much smaller amounts of arachidonate lipoxygenase metabolites, such as leukotriene B4 (LTB4) and 12- and 5-hydroxyeicosatetraenoic acids (HETEs), on stimulation than did AMs from sham rats or untreated rats. However, the concentrations of immunoreactive LTC4 in the BALF of septic rats seemed to be higher than in untreated rats. It is suggested that the AMs of septic rats released lipoxygenase metabolites in alveoli and that these AMs could not be stimulated in vitro. These functional changes in the AMs of septic rats progressed along with the sepsis. These results implicate AMs in the development and progression of septic lung injury by releasing superoxide anions, beta-glucuronidase, and arachidonate metabolites. Furthermore, we speculate that reduced production of LTB4 by septic AMs may increase host susceptibility to severe pulmonary infection during septic ARDS.

Goitrous hypothyroidism with blocking or stimulating thyrotropin binding inhibitor immunoglobulins.

The significance of thyrotropin-binding inhibitor immunoglobulin (TBII) was evaluated in goitrous hypothyroidism associated with chronic thyroiditis (serum TSH greater than 10 mU/L, n = 148). TBII was measured by a RRA, and thyroid-stimulating antibody (TSab) and thyroid-stimulation-blocking antibody (TSBab) were determined using porcine thyroid cells. The prevalence of patients having TBII was 11% or 7.4% of 148 patients, which was not significantly different from that of 5% or 9.6% of 52 patients with atrophic thyroiditis. Although TBII was shown to be TSBab in 6, TSab was found in the other 5 patients despite hypothyroidism. There was little correlation between severity of hypothyroidism and TBII or TSBab activity. One patient continued to be latently hypothyroid despite apparently positive TSBab. Five other patients with TSBab and 2 patients with TSab suffered from overt, irreversible hypothyroidism, and 2 of the patients with TSBab continued to be hypothyroid even after the disappearance of TSBab. Biopsy of the thyroid gland performed in 4 patients revealed severely damaged thyroid follicles with mononuclear cell infiltration with or without fibrosis. Three of the patients with TSab had been taking excess iodine, and recovery of thyroid function was observed after iodine restriction. A perchlorate discharge test performed in two of these patients was positive, suggesting an iodide organification defect. These results indicate that, although TBII is not infrequently found in goitrous hypothyroidism, cellular or chemical damage of the thyroid gland plays an important role in the pathogenesis of thyroid hypofunction and TSBab may only have a precipitating role.

Suppression by interferon-gamma of tumor cell-induced increase in mesothelial permeability.

The effect of interferon-gamma (IFN-gamma) on the interaction between tumor cells and mesothelial cell layers was studied from the aspect of changes in mesothelial permeability. Mesothelial permeability was assessed as the percentage diffusion of radiolabeled albumin across the mesothelial cell sheets on Matrigel-coated filter cup assemblies. When lined gastric carcinoma cells (KATO-III) were seeded on the confluent mesothelial cell layers, the fine cobblestone appearance of the cell sheet was disrupted and mesothelial permeability significantly increased. The increase in permeability was suppressed by the addition of as little as 1 U/ml of IFN-gamma. The effect of IFN-gamma was observed when either the conditioned medium of tumor cells alone or the IFN-gamma-resistant tumor cells, K-562, was placed onto the mesothelium. The cobblestone appearance of the cell sheet was relatively well preserved in the presence of IFN-gamma. In contrast, IFN-alpha did not suppress tumor-induced mesothelial permeability. These results suggest that IFN-gamma has the potential to protect the human mesothelial cell layers against tumor cells.

CEA-mediated homotypic aggregation of human colorectal carcinoma cells in a malignant effusion.

This study was performed to clarify the role of carcinoembryonic antigen (CEA) in the aggregation of colorectal carcinoma (CRC) cells in malignant effusions. We analysed freshly purified CRC cells from one patient, which expressed CEA (98% positive cells) on the surface and formed huge cell aggregates in the patient's ascites. The carcinoma cells expressed Sialyl Lewis A (82%), Sialyl Lewis X (92%) and the beta 1 integrin subunit (78%) but did not express the pair-ligands for these molecules. Cell aggregation was completely inhibited by anti-CEA mAb. The decreased CEA expression induced by phosphatidylinositol-specific phospholipase C (PI-PLC) treatment led to decreased cell aggregation. We also examined the correlation between the degree of cell aggregation and CEA expression using smears of ascites fluid from 27 patients with colorectal cancer. There was a significant correlation between the degree of cell aggregation and CEA expression by CRC cells. The present study provided the first evidence that CEA molecules mediate the homotypic aggregation of CRC cells in malignant effusions.

Immunotherapy of cancer patients with Bacillus Calmette-Guérin: summary of four years of experience in Japan.

Active immunotherapy with living BCG was conducted on 98 patients with various types of cancer. The candidates for this therapy were patients with residual or inoperable cancer of the colorectum, liver, breast, biliary tract, lung, and other organs with a follow-up of 4-58 months. Eleven of the 98 (11%) were able to survive for as long as 37-58 months (mean survival time 42.5 months) because of this treatment and are still living. Another 11 patients are also alive more than 24 months after starting treatment. Thirty-seven patients, however, succumbed within 12 months despite BCG immunotherapy. On the other hand, 37 patients in the control group, who shared the same clinical status and did not receive BCG therapy during this period, underwent unhappy courses for 2-12 months (mean survival time 8.7 months). The pretreatment immunoresponsiveness of these 98 patients was suppressed, as measured by the following immunologic parameters: T-cell subpopulation in the peripheral blood, stimulation index of PHA, and skin tests to DNCB, KLH, PPD, and PHA. All of these parameters improved shortly after initiation of BCG injections in 22 patients who survived more than 24 months. In contrast, in patients who died within 12 months, immunoresponsiveness remained suppressed throughout the course. This result has suggested that there was an apparent correlation between the effectiveness of BCG and immunoresponsiveness. In addition, a good correlation was observed between the duration of inflammatory reactions at BCG injection sites and clinical prognoses. Moreover, it was shown that a relatively high amount of BCG (20-80 mg as an initial dosage) and repeated injections of living BCG were necessary to obtain a sufficient enhancing effect on the immunocompetency of these late-stage cancer patients. The most conventional criterion used to determine an optimal time for booster injections of BCG was measurement of the PPD-evoked skin reaction at the BCG injection site, that is, Koch's phenomenon. When a marked flare-up reaction of more than 2.5 X 2.5 cm in size was observed, the effect of BCG was considered to be continuing, and no additional booster injection was needed. The mean interval between the first and second BCG injections was 6.2+/-1.1 months in patients who survived more than 2 years. In contrast, the duration of this reaction was only transient in ineffective cases. The most frequent side effects of this therapy were fever and malaise; these complications occurred in 62% of the cases. No severe side effects, such as dissemination, anaphylactic shock, or granulomatous hepatitis, have been experienced throughout this study, even in patients to whom a total dosage of more than 200 mg of living BCG were injected.

New approach to management of malignant ascites with streptococcal preparation OK-432. III. OK-432 attracts natural killer cells through a chemotactic factor released from activated neutrophils.

When a streptococcal preparation, OK-432, was administered intraperitoneally to patients with malignant ascites, lymphocytes with cytotoxic activity against tumor cells increased in number in the peritoneal cavity after 5 to 7 days. To investigate the underlying mechanisms of such lymphocyte accumulation, lymphocyte chemotactic activity (LCA) in ascitic fluid was measured by a modification of the Boyden method. High LCA was found on the third and fourth days after the OK-432 injection. This LCA was generated in the cell-free supernatant of the patients' abdominal neutrophils that accumulated in the peritoneal cavity 24 hours after the injection of OK-432. A similar LCA was also found when normal peripheral neutrophils were incubated with OK-432. Incubation of normal neutrophils without OK-432 failed to generate LCA, however, and OK-432 alone had no LCA. We tentatively named this factor "neutrophil-derived lymphocyte chemotactic factor" (NDLCF). The NDLCF was heat stable and nondializable, and its molecular weight was approximately 45,000 daltons. It attracted mainly natural killer cells by immunoperoxidase assay of migrated lymphocytes in the chemotactic membrane. These characteristics were distinct from C5a, interleukin-1, and interleukin-2. The results suggest that the newly found NDLCF may be responsible for the infiltration of cytotoxic lymphocytes, especially natural killer cells in the peritoneal cavity in patients with malignant ascites when treated by intraperitoneal injections of OK-432.

Immunologic studies on myasthenia gravis. II: A new chemotactic factor for lymphocytes found in patients with myasthenia gravis.

A specific chemotactic factor for lymphocytes was found in thymic tissue extract from myasthenic patients who had undergone thymectomy. Biologic activities and the biochemical nature of this factor were examined. The major findings were as follows: (1) The factor from myasthenic thymus was specifically chemotactic for T lymphocytes. Marker analysis of target cells revealed that only OKT4 positive cells (helper/inducer T cells) responded to the factor. Chemotactic activity was also found in the normal thymus, but its activity was different from that found in the myasthenic thymus. Interestingly, OKT8 positive cells (suppressor/cytotoxic T cells), as well as OKT4 positive cells, migrated toward the normal thymic extract (2) Chromatography of the extract by gel filtration gave three peaks with chemotactic activity; molecular size were 160,000 to 100,000, 25,000 to 15,000, and smaller than 1350 daltons (3) The factor was inactivated by heating for 30 minutes at 56 degree C and was also destroyed under conditions of pH 4 and pH 10. The factor was also sensitive to treatment by trypsin, sodium metaperiodata, 8 mol/L urea, reduction, or alkylation. (4) The chemotactic activity in the myasthenic thymus was distinct from other known chemotactic factors, including C5a, interleukin-1, and interleukin-2. (5) Chemotactic activity for lymphocytes was found in both the aqueous extract and the culture supernatant of thymic stromal cells, but not in thymocyte extract or in the serum. These findings indicate that the chemotactic factor specific for OKT4 positive cells may be secreted by stromal cells of the myasthenic thymus but not of the normal thymus.

The role of eosinophils in interleukin-2/lymphokine-activated killer cell therapy.

When interleukin-2 alone or in combination with lymphokine-activated killer (LAK) cells is administered to patients with cancer, peripheral or local eosinophilia is frequently seen. To evaluate the role of eosinophils in this setting, we studied the functional changes of human eosinophils induced by the supernatant of LAK cell cultures. The chemotactic activity, change in chemiluminescence, superoxide production, expression of leukocyte integrins (CD11/CD18 family), and adherent activity to plastic dishes were investigated after stimulation of eosinophils with LAK cell culture supernatant. The chemotactic activity of eosinophils in the supernatant of LAK cell cultures was increased significantly, and this activity was chemotactic rather than chemokinetic by checkerboard analysis. Both chemiluminescence and superoxide production of stimulated eosinophils increased significantly compared with resting. In addition, eosinophil-adherent activity to plastic dishes was also increased. Among leukocyte integrins, CD11b expression on stimulated eosinophils increased. Moreover, eosinophil antibody-dependent cellular cytotoxicity against Raji cells was enhanced after stimulation with the supernatant of LAK cell cultures. These results suggest that the eosinophils activated by LAK cells may play an important role in the antitumor effect of interleukin-2/LAK cell therapy.

New approach to management of malignant ascites with a streptococcal preparation, OK-432. II. Intraperitoneal inflammatory cell-mediated tumor cell destruction.

Twelve patients with malignant ascites caused by gastric cancer were treated with intraperitoneal injections of a streptococcal preparation, OK-432. All had resolution of the ascites after OK-432 treatment. Neutrophils, macrophages, and lymphocytes increased in number in ascitic fluid samples. Some of the OK-432-induced inflammatory cells were attached to tumor cells. The absolute number of tumor cells decreased as the number of infiltrating inflammatory cells increased. Infiltrating lymphocytes were mainly E rosette-forming cells. Infiltrating macrophages were in an activated state. The infiltrating neutrophils, lymphocytes, and macrophages could inhibit DNA synthesis of the patient's own tumor cells in the ascitic fluid after OK-432 injection, but not before the injection. These results indicate that OK-432-induced neutrophils, lymphocytes, probably T cells, and activated macrophages may play an important role in tumor cell destruction in ascites. Moreover, as the number of tumor cells decreased, the ascitic fluid protein levels decreased. Decrease of the ascitic fluid protein level may suppress further accumulation of ascitic fluid, and the low protein level in ascitic fluid is likely to facilitate the reabsorption of the fluid into the bloodstream.

Immunologic assessment of host defense impairment in patients with septic multiple organ failure: relationship between complement activation and changes in neutrophil function.

BACKGROUND: The pathogenesis of gram-negative sepsis-induced multiple organ failure (MOF) remains to be elucidated. METHODS: Blood samples were obtained from eleven patients with septic MOF, three patients with sepsis, three patients who underwent operation, and three healthy volunteers. In these patients the relationship between changes in polymorphonuclear neutrophil (PMN) function and complement activation was investigated. RESULTS: PMNs from patients with sepsis exhibited enhanced endothelial cell adhesion, enhanced chemotaxis, increased oxygen radical generation, and increased lysosomal enzyme release. Although PMNs from patients with septic MOF also exhibited enhanced adhesion and chemical mediator production, chemotaxis was markedly depressed. Complement activation in septic MOF was indicated by decreases in total complement activity and complement component 4 (C4) and increases in C3a and C4a des-Arginine. Increases in plasma concentrations of circulating immunoglobulin G immune complexes and decreases in PMN Fc gamma R expression suggest that the classic pathway is the main pathway of complement activation. On the other hand, we could not detect decreases in C4 or increases in C4a des-Arginine in patients with sepsis, suggesting that the alternate pathway is the main pathway of complement activation. Increases in serum concentrations of the membrane attack (SC5b-9) complex also suggested that activated complement itself may participate in organ injury in patients with septic MOF. Moreover, PMN up-regulation of surface inhibitory factors of complement activation likely allows these neutrophils to survive and function. CONCLUSIONS: The combination of changes in PMN function and complement activation appears to be intimately associated with the pathogenesis of septic MOF.

Abnormal lipoprotein appearing in plasma of patients who received a ten percent soybean oil emulsion infusion.

In 42 of 43 surgical patients who received a 10% soybeam oil emulsion (Intralipid), abnormal lipoprotein was detected in their plasma 1 to 2 days after the initial Intralipid infusion. This abnormal lipoprotein was proven to appear as a result of the infusion of soybean oil emulsion regardless of the patient's original diseases, age, sex, liver function, or concomitantly administered solutions. In addition, this abnormal -ipoprotein was found to have various similarities to lipoprotein-X (LP-X) which is found in plasma from patients with obstructive jaundice or familial lecithin:cholesterol acyltransferase deficiency. Therefore, this abnormal lipoprotein was tentatively named LP-X--like substance (LP-X-LS). A comparison of the properties of LP-X and LP-X-LS was performed and the following results were obtained: (1) LP-X-LS migrated toward the cathode on Bacto-Agar gel electrophoresis similarly to LP-X; (2) the stability of LP-X and LP-X-LS against heating and freezing were almost equal under various conditions; (3) LP-X-LS could be absorbed by anti--LP-X serum; (4) LP-X-LS existed in low density fraction (d = 1.063) separated by ultracentrifugation from plasma; (5) electron microscopic study of low-density lipoprotein particles from LP-X-LS positive plasma revealed that LP-X-LS had a similar ultrastructure to LP-X. From these results it is suggested that LP-X-LS is an abnormal lipoprotein quite similar to LP-X.

Immunological studies on myasthenia gravis: operative indication and cell-mediated immunity.

An important aspect of the management of patients with myasthenia gravis is the decision to recommend thymectomy. Hitherto, many investigators have reported the relationship between the operative effects and such factors as age, sex, duration of symptoms, or degree of germinal center proliferation in the myasthenic thymus. However, these reports are not practical aids in deciding the indication for thymectomy in an individual myasthenic patient. The currently accepted indications of thymectomy for myasthenic patients are (1) the thymomatous patient, especially those with malignancy, and (2) the nonthymomatous patients who are resistant to medical treatment. From our present data we would add the following as an indication of the operation: (3) patients who have high T-cell subpopulation levels with highly blastogenic activities and strong skin test reactivities. In order to assure good operative results in myasthenic patients, surgeons should examine their patients' preoperative immunological states.

Vascular endothelial growth factor and platelet-derived growth factor are potential angiogenic and metastatic factors in human breast cancer.

BACKGROUND: Angiogenesis is a prerequisite for tumor growth and metastasis. Tumor angiogenesis may be mediated by several angiogenic factors such as vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), transforming growth factor-alpha, and basic fibroblast growth factor. METHODS: Differential mRNA expressions of VEGF, PDGF (A chain), transforming growth factor-alpha and basic fibroblast growth factor in 32 primary invasive breast tumors were examined by reverse transcriptase-polymerase chain reaction. We analyzed relationships between mRNA expressions of these angiogenic factors and the degree of angiogenesis, tumor size, and metastasis. Quantification of angiogenesis was achieved by the immunohistochemical staining of endothelial cells with antibody to CD31. RESULTS: VEGF and PDGF-A mRNAs were expressed more frequently in breast tumors than in nontumor breast tissues, whereas no difference was found in expression frequency of either transforming growth factor-alpha or basic fibroblast growth factor mRNA. Vascular counts in tumors correlated with each expression frequency of VEGF and PDGF-A mRNA. PDGF-A mRNA was expressed more frequently in tumors with lymph node metastasis than in those without metastasis. CONCLUSIONS: Expression of VEGF and PDGF mRNAs detected by reverse transcriptase-polymerase chain reaction in breast tumors correlates with tumor-related characteristics of angiogenesis and metastatic potential. Analysis of these mRNAs by reverse transcriptase-polymerase chain reaction may be useful for assessing the biologic behavior of a breast tumor before surgical treatment.

Acid protease activity in thyroid gland from patients with Graves' disease.

Although the activity of lysosomal protease in Graves' thyroid is considered to be increased, there has been no quantitative method to estimate the protease activity in the thyroid tissue due to the contamination of thyroglobulin (Tg) which varies in susceptibility to the protease. In the present study, the proteolytic activity (PA) of thyroid lysosomal protease preparation (P25) separated from Tg was assayed using 125I labeled rat Tg. More than 95% of 125I-Tg was hydrolyzed at pH 4.0 without deiodination, and the pattern of liberated iodoamino acids resembled that of pronase digest except for a higher T3/T4 ratio. Thirty-seven Graves' thyroids and 15 paranodular thyroid tissues were assayed. PA, the specific PA (SPA; calculated as PA per mg P25 protein) and PA per DNA content in Graves' thyroids were significantly higher than those in controls. There were good correlations among PA, SPA and PA per DNA content of the thyroid tissue. PA and SPA in the thyroid from 29 patients with Graves' disease treated with propylthiouracil or methimazole did not correlate with serum thyroid hormone level immediately before surgery. In 8 patients treated with KI, PA from 5 patients whose serum thyroid hormone levels had been normalized were significantly lower than those from 3 patients who were still thyrotoxic.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of the effects of steroids on experimental septic lung injury.

To evaluate the clinical usefulness of steroids for septic lung injury, we investigated the effects of methylprednisolone (MP) on this disorder using an experimental rat model of cecal ligation and puncture (CLP). While 92% of the rats that underwent CLP (CLP rats) died within 30 h, those given high-dose MP (30 mg/kg) just after the operation (CLP + MP rats) survived for a significantly longer period (p < 0.01). Concentrations of endotoxin (ET) in arterial blood were significantly higher in the CLP + MP rats than in the CLP rats, while those in the bronchoalveolar lavage fluid (BALF) were significantly lower. Alveolar macrophages (AM) obtained from the CLP rats (CLP-AM) generated more O2-than did AM from sham-operated rats (sham-AM) following stimulation. However, the administration of MP did not reduce the upregulated generation of O2-by CLP-AM. While CLP-AM produced less leukotriene (LT)B4 than did sham-AM following stimulation with A23187, the administration of MP further reduced LTB4 production. When AM were cultured with [3H]arachidonic acid (3H-AA), the uptake of the isotope and the 3H release were significantly less in CLP-AM than in sham-AM. The administration of MP did not cause recoveries in the uptake and release of 3H-AA by CLP-AM. Although the survival time of CLP rats was significantly prolonged and the translocation of ET into BALF was reduced by steroid administration, the steroid effects were not explained by those on altered AM function. The upregulated generation of O2- and reduced LTB4 production from CLP-AM were not reversed by the treatment of this drug.

The order of ward rounds influences nosocomial infection. A 2-year study in gastroenterologic surgery patients.

We studied the effect of the order of ward rounds on nosocomial infection in gastroenterologic surgery patients. The subjects were patients with gastrointestinal diseases admitted between September 1992 and August 1994. During the 1st year, the round proceeded indiscriminately among recovery rooms and rooms with stable patients and isolated patients with methicillin-resistant Staphylococcus aureus (MRSA). In the subsequent year, the round started in the recovery rooms and moved into the general rooms with stable patients and finally into the isolation rooms. Against the time course, piecewise linear regression analyses were made with the number of culture-positive patients and the quantities of antibiotics and disinfectants used. Of a total of 1894 strains from 264 patients, isolates of MRSA (n = 200) decreased from 150 in the 1st year to 50 in the 2nd year. The number of MRSA-positive patients showed the point of inflexion in the analysis at the change of round order, with a later decrease. The trend was similar for Candida (n = 99) and Enterococcal (n = 225) species. The amount of antibiotics was unchanged while the amount of disinfectants used decreased in the 2nd year. Thus, the round re-ordering appeared to help prevent nosocomial infection. Ward rounds for patients who have had gastroenterologic surgery should proceed from compromised hosts to stable patients, and then isolated patients.