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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An experimental model was designed to evaluate a combined protocol of active immunization and granulocyte transfusions for treatment of Pseudomonas aeruginosa sepsis in the neutropenic host. One member of a pair of dogs was immunized with P. aeruginosa vaccine. Both dogs were then rendered transiently neutropenic with a single intravenous dose of cyclophosphamide (40 mg. per kilogram) and challenged with an intravenous inoculum of P. aeruginosa. Twenty-four and 48 hours after pseudomonas challenge each animal received granulocyte transfusions. Effectiveness of therapy was evaluated by observation of survival time, febrile response, and quantitative blood cultures. Results showed a significant increase in the survival period (P is less than 0.05), a lower febrile response (P is less than 0.025), negative blood cultures, and a greater recovery rate in the immune group. Immune dogs that died had negative blood cultures or less than or equal to 10 pseudomonas per milliliter of blood despite the presence of P. aeruginosa in tissues. In contrast, control dogs had septic deaths within 67 hours of pseudomonas challenge, marked febrile responses with 24 hours of infection, and positive blood cultures with 4,000 to 25,800 pseudomonas per milliliter of blood. These data show that combined therapy with immunization and granulocyte transfusions is effective in reducing the severity of P. aeruginosa infection and in preventing bacteremia during periods of leukopenia.
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PMID:Combined pre-immunization and granulocyte transfusion therapy for treatment of pseudomonas septicemia in neutropenic dogs. 127 Aug 91

Between August 1985 and June 1986, 49 previously untreated patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC) were treated with the combination of cisplatin 80 mg/m2 i.v. on day 1, vindesine 3 mg/m2 i.v. on days 1 and 8, and mitomycin-C 8 mg/m2 i.v. on day 1 (MVP), repeating after an interval of 4 weeks, and thereafter every 6 weeks. The median age for all patients was 62 years, with a range of 21 to 77 years. All patients had a performance status of 0, 1, or 2 (ECOG scale) and measurable disease. Histologic types included squamous cell carcinoma (22 patients), adenocarcinoma (22 patients), and large-cell carcinoma (6 patients). Forty-eight patients were evaluable for response. Out of 48 patients, one (2%) achieved a complete response and 24 patients (50%) achieved a partial response, resulting in an overall response rate of 52% (95% confidence interval, 38-68%). The response rates were 52% for squamous cell carcinoma, 45% for adenocarcinoma, and 80% for large-cell carcinoma, respectively. The median duration of response was 4.2 months and the median duration of survival for all patients was 10.6 months. The major toxicity was myelosuppression. Leukopenia and thrombocytopenia of grade 3 or 4 occurred in 85% and 33%, respectively. One patient died of sepsis associated with leukopenia. Other toxicities were manageable and reversible. In conclusion, the MVP regimen was active and tolerable in patients with advanced NSCLC. Prospective randomized study comparing the MVP regimen with the two-drug combination of vindesine and cisplatin is warranted.
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PMID:Mitomycin C, vindesine, and cisplatin in advanced non-small-cell lung cancer. A phase II study. 131 68

Pneumococci (Streptococcus pneumoniae) infrequently cause neonatal septicemia. An increased number of cases have been reported in recent years, but no increase in the relative incidence among neonatal infections has been noted. On the basis of two cases of our own and a review of 40 recently published case reports, the clinical characteristics of pneumococcal septicemia are described and the pathogenesis is discussed. The presenting clinical picture in early-onset pneumococcal septicemia is dominated by respiratory distress, frequently accompanied by leukopenia, and is indistinguishable from that seen in septicemia caused by Group B Streptococci (GBS). The onset is preceded by prelabor rupture of the fetal membranes in almost half of the instances. The mortality is 50%, twice the figure given in recent GBS reports.
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PMID:Neonatal septicemia caused by pneumococci. 131 1

Both gram-negative infection and bacterial endotoxin (lipopolysaccharide, LPS) produce a marked neutropenia and increase glucose disposal by peripheral tissues. The purpose of the present study was to determine whether leukocyte depletion before these insults would diminish the commonly observed increases in tissue glucose uptake. Rats were depleted of circulating and marginated leukocytes with cyclophosphamide (CPA). Under basal postabsorptive conditions the subcutaneous injection of live Escherichia coli into control animals enhanced whole body glucose disposal that resulted in part from a stimulation of glucose uptake by the liver, spleen, intestine, and lung. These increases in tissue glucose uptake were not associated with an increase in neutrophil number, as assessed by myeloperoxidase (MPO) activity. CPA-induced leukopenia did not alter the sepsis-induced increase in glucose uptake by these tissues and whole body glucose use remained elevated. In contrast, skin and muscle proximal to the site of infection showed an increase in both glucose uptake and MPO activity. Furthermore, leukocyte depletion attenuated the elevated glucose uptake by skin and muscle near the inflammatory focus. The intravenous injection of LPS also increased whole body glucose disposal and enhanced glucose uptake by the lung, liver, spleen, intestine, and skin in saline-treated rats. Of these tissues the lung, liver, and spleen had a corresponding increase in neutrophil number. The LPS-induced increases in tissue glucose uptake in leukopenic rats were comparable, with the exception of liver and lung. In these tissues the incremental increase in glucose uptake after LPS was reduced 40-50% in leukopenic animals.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Sepsis- and endotoxin-induced increase in organ glucose uptake in leukocyte-depleted rats. 133 18

Administration of free muramyl tripeptide phosphatidylethanolamide (MTPPE) or liposome-encapsulated MTPPE (LE-MTPPE) in a twofold-lower dose at 24 h before bacterial inoculation resulted in clearance of intravenously inoculated Klebsiella pneumoniae by tissue macrophages, whereas in control mice, bacteria were not effectively cleared from the blood. In addition, MTPPE and LE-MTPPE led to increased numbers of leukocytes in the blood, which could compensate for the leukopenia in mice resulting from infection with K. pneumoniae. In an attempt to elucidate the relative contributions of the activation of tissue macrophages and the recruitment of leukocytes to the antibacterial resistance induced by MTPPE and LE-MTPPE, mice were infected intraperitoneally with K. pneumoniae. In these MTPPE- and LE-MTPPE treated mice, intraperitoneal influx of leukocytes and the phagocytic capacity of leukocytes were not higher than in untreated control mice. However, MTPPE- and LE-MTPPE-treated mice survived much longer; eventually 33% of the LE-MTPPE-treated mice survived, whereas all untreated control mice died as a result of bacterial septicemia. This prevention of early death appeared to be the result of an increased clearance of bacteria from the blood by activated tissue macrophages. It was observed that depletion of these tissue macrophages in liver and spleen abrogates the effect of LE-MTPPE treatment, indicating that tissue macrophages are of major importance in the LE-MTPPE-induced resistance against K. pneumoniae infection.
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PMID:Roles of peripheral leukocytes and tissue macrophages in antibacterial resistance induced by free or liposome-encapsulated muramyl tripeptide phosphatidylethanolamide. 139

38 patients with advanced breast adenocarcinoma were treated in a phase II study with 5-fluorouracil and high-dose folinic acid combined with cyclophosphamide and mitoxantrone. 6 patients had received prior chemotherapy for advanced disease, all with an anthracycline-containing regimen. Treatment was generally well tolerated. The most common side-effect was myelosuppression, with 1 toxic death due to leukopenia-related sepsis. 1 patient developed severe congestive heart failure 12 months from the end of therapy. 36 patients were evaluable for response. The overall response rate was 55%. Median duration of response was 8 months and median survival time was 16 months. This regimen warrants further investigations.
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PMID:A phase II study of 5-fluorouracil and high-dose folinic acid in combination with cyclophosphamide and mitoxantrone for advanced breast cancer. 141 91

Twenty one patients with hormone resistant prostate cancer were entered in a phase II study of pirarubicin 70 mg/m2, as a single intravenous injection given at 21 day intervals. All patients had leukopenia (9 severe or life threatening) and 2 died of septicemia. Thrombocytopenia occurred in 5 patients (one life threatening) and anemia in 12 patients. One partial response of 3 months duration was documented. Pirarubicin 70 mg/m2 given intravenously at 21 day intervals causes severe hematological toxicity and has minimal therapeutic activity in patients with hormone resistant prostate cancer.
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PMID:Phase II clinical study of pirarubicin in hormone resistant prostate cancer. 150 Feb 66

A total of 378 serum samples from 240 hospitalized horses and 47 sera from healthy control horses were assayed for growth effects on actinomycin D-treated L929 cells. On average, patient and control sera stimulated cell growth; however, mean percentage of the relative growth index (RGI) of sera from clinical cases was significantly (P less than 0.001) lower than that of control sera. Approximately 35% of patient sera and 6% of control sera had tumor necrosis factor-like cytotoxic activity for L929 cells (ie, RGI less than 100%). Sera from horses with either peritoneal leakage of gastrointestinal tract contents or any bacterial infection were significantly (P less than 0.05) more cytotoxic than sera from horses that did not have these clinical factors. A clear tendency was evident for horses that had the highest serum cytotoxicity (RGI less than 75%) to also have clinical profiles suggestive of endotoxemia. Fever, leukopenia, diarrhea, and gastrointestinal tract leakage were significantly (P less than 0.05) overrepresented among these horses, compared with horses without serum cytotoxicity. Bacterial infections and abdominal surgeries were also increased in this group, but not significantly. Of the 14 horses with serum RGI less than 75%, 13 had some form of gastrointestinal tract disease and the other had gram-negative septicemia. Survival to discharge was significantly (P less than 0.05) lower among horses in the high-cytotoxicity group than among horses without serum cytotoxicity. Diarrhea and bacterial infections were the only clinical factors found more frequently in horses with low serum cytotoxicity than in horses without serum cytotoxicity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Association between serum cytotoxicity and selected clinical variables in 240 horses admitted to a veterinary hospital. 152

We conducted a phase I/II trial of 5-fluorouracil (5-FU)/folinic acid (FA) and alpha-2b interferon (IFN) in 43 previously untreated patients with measurable metastatic colorectal cancer. Patients had disease progression prior to therapy consistent of 5-FU 500 mg/m2 (level A) or 600 mg/m2 (level B) as starting dose administered as a 2-hour infusion, FA 200 mg/m2, and alpha-2b IFN 5MU/m2 subcutaneously. All drugs were given on days 1 to 5 and cycles were repeated after 3 to 4 weeks. The aim of the study was to define the maximal tolerable dose (MTD) of 5-FU for this schedule. In the absence of toxicity above MTD, defined as diarrhea and mucositis of World Health Organization grade 2 and leukopenia of World Health Organization, grade 3 5-FU was increased in increments of 100 mg/m2 for further cycles. Twenty-four patients were started on level A; 18 were started on level B. Forty-two patients were evaluable for toxicity, 32 for response. Three of 32 patients achieved a partial response; in 22 of 32 patients, tumor stabilization occurred. Forty percent of patients started on level A developed grade 2 diarrhea; 28% of patients developed grade 2 or 3 mucositis. Of 18 patients on level B, two patients experienced grade 4 mucositis (11%) and grade 3 or 4 diarrhea (11%). One drug-related death in the presence of sepsis occurred. Due to 11% of patients with grade 4 toxicity when started on 600 mg/m2 5-FU and 40% of patients with grade 2 diarrhea when started on level A, MTD as starting dose for 5-FU is 500 mg/m2 as a 2-hour infusion when used in combination with FA and IFN on a day 1 to 5 active schedule. We observed a wide range of 5-FU dose tolerated by individual patients. While some patients experienced severe, mainly gastrointestinal, toxicity on lower levels of 5-FU, others tolerated much higher 5-FU doses (11 patients, 700 mg/m2; 5 patients, 800 mg/m2; and one patient, 900 mg/m2). Our data suggest that double modulation of 5-FU by FA and IFN may not be superior to modulation of 5-FU with either drug alone.
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PMID:Interferon alpha-2b, 5-fluorouracil, and folinic acid combination therapy in advanced colorectal cancer: preliminary results of a phase I/II trial. 155 46

Human pneumococcal septicemia, the prominent postsplenectomy complication, was as yet difficult to study in the porcine model, since this species appeared to be fairly resistant against pneumococcal infections. We have used two strains of pneumococci (serotype 1 and 6B) both of which had been isolated from patients with systemic infection and both of which were maintained in a virulent state by regular mouse passage. After challenge with 10(9) type 1 pneumococci, however, only one of the 5 pigs developed fever, none showed profound hematological alterations and each animal exhibited a rapid clearance of bacteria from peripheral blood. By contrast, challenge of 7 animals with type 6B pneumococci resulted in a slower and incomplete bacterial clearance with persistent bacteremia for up to 24 hours. All animals developed fever and a profound leukopenia with less than 5,000 leukocytes/ml and 3 of the 7 animals died after injection of type 6B pneumococci. The results show that potentially the type 6B pneumococci can be successfully employed for studies of gram positive septicemia in the miniature swine.
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PMID:Establishment of a pneumococcal septicemia model in the miniature swine. 159 38


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