Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0243026 (sepsis)
 52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ceftriaxone has a very long serum half-life and enhanced in vitro activity against common pediatric pathogens. Therefore we evaluated the efficacy and safety of once daily ceftriaxone therapy in 57 children with serious infections including: meningitis (26 patients); ventriculitis (3); pyelonephritis (7); osteomyelitis (6); abscess (4); septic arthritis (3); sepsis (2); and miscellaneous infections (6). The most common isolates were Haemophilus influenzae (23), Escherichia coli (9) and Staphylococcus aureus (8). Ceftriaxone was given intravenously or intramuscularly in a dose of 50 mg/kg for non-central nervous system (CNS) infections. Patients with CNS infections received an initial dose of 100 mg/kg followed by 80 mg/kg 12 hours later and once daily thereafter. In a limited number of patients no major differences in serum ceftriaxone concentrations were found after intravenous or intramuscular injection. Of 57 patients with pathogens isolated 55 were completely cured; in one patient with Klebsiella pneumoniae ventriculitis, intraventricular gentamicin was briefly added to the regimen. Another patient with an anaerobic liver abscess recovered after metronidazole was administered. In three patients a delayed response to ceftriaxone was noted. One patient with previous recurrent infections had a second episode of H. influenzae meningitis 22 days after cessation of therapy. Clinical side effects were noted in 10 of 71 patients (including 14 treated patients who had negative cultures). Seven patients had diarrhea, one each had fever or rash and one had fever, rash and arthralgia. Laboratory side effects in 16 of 71 patients included eosinophilia (7), thrombocytosis (7), elevated liver enzymes (4) and leukopenia and neutropenia (2).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Once daily ceftriaxone for central nervous system infections and other serious pediatric infections. 372 39

A phase II study of acute leukemia with mitoxantrone (MIT) was conducted by the Tokai Blood Cancer Study Group. The drug efficacy was evaluable in 31 cases (14 of ALL and 17 of ANLL) out of 37 entered at 13 institutions. Five cases were for first induction remission and 26 cases for re-induction remission; ages ranged from 7 to 69 (median: 43); 18 males and 13 females. MIT dosage was intravenous injection of 3-6 mg/m2/day X 5 consecutive days as a rule. Of the 14 cases of ALL, 2 achieved CR and 3, PR; the efficacy rate was 36%. Of the 17 cases of ANLL, 4 achieved CR and 3, PR: the efficacy rate was 41%. Of the 5 first induction remission cases, 3 achieved CR, and 1, PR, the efficacy rate being 80%, whereas out of the 26 re-induction remission cases, 3 achieved CR, 5 PR, and the efficacy rate was 31%. In 3 of 6 cases of CR, large cumulative doses of anthracyclines such as DNR 140 mg plus ACR 410 mg, DNR 360 mg plus ADR 120 mg plus ADR 120 mg, and DNR 240 mg plus ADR 540 mg, had been administered previously in each case. As to complications, sepsis and other infections were observed at the rates of 15% and 32%, respectively, from which it was inferred that in therapy with mitoxantrone, leukopenia should be observed carefully. The major non-hematological toxicity was gastrointestinal symptoms, but the degree was mild. From the results of this trial, it was concluded that mitoxantrone was an effective form of therapy for acute leukemia. Further clinical trials on mitoxantrone in combination with other drugs are scheduled.
 ...
PMID:[Phase II study of mitoxantrone in patients with acute leukemia]. 374 Aug 58

Twenty-two patients with metastatic colorectal cancer were treated with a regimen of 5-fluorouracil 600 mg/m2 (maximum, 1.0 g) i.v./week and folic acid 140 mg/m2 i.v. given 1 h prior to the 5-FU. This study was undertaken in an attempt to confirm the in vitro finding that inhibition of thymidylate synthetase by 5-fluorouracil is prolonged by the presence of folates. There were four partial responses (18%) with mean duration 4 months. Dose-limiting toxicity was enteritis, seen in 12 patients (58%), and causing hospitalization in seven patients. Enteritis was shown to be due to the folic acid in most patients. Two patients died from leukopenia, enteritis, and sepsis. Mean serum folate levels at the time of 5-FU injection were 36 microM. This regimen is no more effective than 5-FU alone and has significantly more serious toxicity. Further investigation of this regimen is not recommended.
 ...
PMID:5-Fluorouracil and high-dose folic acid treatment for metastatic colon cancer. 382 92

A prospective study was conducted to evaluate response rate and toxicity of the combination of cyclophosphamide, adriamycin, and cis-platinum in patients with disseminated hormonally resistant prostatic carcinoma. Twenty-two patients were entered in the study: 19 were evaluable for response. One patient achieved partial remission while 14 (73%) had stable disease. Four patients had progressive disease. Patients with stable disease and partial remission had subjective improvement and survived significantly (p less than 0.03) longer than patients with progressive disease (58 weeks vs. 22 weeks). Toxicity was mainly hematological, and one patient died from sepsis secondary to leukopenia. Nausea and vomiting was moderate to severe, with one patient refusing cis-platinum for that reason. Renal toxicity was tolerable and reversible. Lack of good measurable disease makes generalization difficult, but pointers from animal models, along with the biological activity suggested by our results, make this a worthwhile combination to be considered for a trial in a larger population with measurable disease or in a randomized trial vs. the more effective single agent.
 ...
PMID:Evaluation of cyclophosphamide, adriamycin, and cis-platinum (CAP) in patients with disseminated prostatic carcinoma. A phase II study. 384 Mar 26

Antiserum raised to a rough mutant Escherichia coli, termed J5 (anti-J5 RS), protected against lethal gram-negative bacterial sepsis in a guinea pig model when animals were pretreated with both antiserum and heparin. This same model was used to examine and compare the effects of pretreatment with anti-J5 RS, normal rabbit serum (NRS), or saline, each +/- heparin on physiologic and metabolic parameters during a septic insult. Results demonstrated that leukopenia and thrombocytopenia occurred to a similar degree in all pretreatment groups; no significant leuko- or thrombostasis was noted on examination of histologic specimens; complement activation was maximal in those animals receiving anti-J5 RS alone without heparin; the most abnormal amino acid profile was present in the NRS + heparin group; and only the anti-J5 RS + heparin group did not develop glomerular lesions indicative of disseminated intravascular coagulation. A complement-mediated cell aggregation-type injury does not appear to occur in this model. It is hypothesized that both excessive complement and coagulation system activation occur after bacterial challenge when antibody directed against the bacteria is present (anti-J5 RS) leading to antigen-antibody complex formation and complement and coagulation cascade activation. Heparin may block either or both these cascade systems allowing enhanced, antibody-mediated opsonization and clearance of blood-borne bacteria, thus preventing end-organ alterations and organ failure during sepsis when combined with anti-J5 RS.
 ...
PMID:Metabolic effects of pretreatment with Escherichia coli J5 antiserum on guinea pig gram-negative bacterial sepsis. 388 2

Preliminary evidence (n = 15) with semiquantitative (latex) determinations of C-reactive protein (CRP) suggested an unreliable CRP response in systemic Group B streptococcal infection. Recent experience with sequential, quantitative determinations of CRP in 10 infants surviving GBS infection documents that CRP can rise rapidly with systemic infection and fall rapidly with appropriate treatment. One infant with asymptomatic bacteremia had no increase in CRP, but in nine others with sepsis and/or meningitis the peak concentrations were from 4.2 to 31.9 mg/dl. Duration of elevated CRP ranged from 2 days in benign illness to 17 days in severe meningitis. Two infants with neurologic sequelae had concentrations greater than 20 mg/dl. Leukopenia, neutropenia and elevated immature neutrophil:total neutrophil ratio were frequently observed at the onset of infection. Leukocyte counts may be most helpful in making an early diagnosis, whereas CRP concentrations may document response, influence duration of antibiotic therapy and provide prognostic information.
 ...
PMID:Response of C-reactive protein in neonatal Group B streptococcal infection. 388 78

Forty-four patients with non-small cell carcinoma of the lung were treated every 3 weeks with vinblastine (4 mg/m2/day iv X 2) and cisplatin (20 mg/m2/day iv X 3). Of the 28 patients with metastatic disease, eight (29%; 90% confidence interval of true response, 17%-47%) achieved objective response, for a median duration of 27 weeks. Median survival in this group was 47 and 28 weeks for responders and nonresponders, respectively. Of the 16 patients with advanced regional disease, 11 (69%; 90% confidence interval of true response, 49%-86%) achieved objective response. Thirteen of these patients received consolidation radiotherapy (4500 cGy/25 fractions/5 weeks), with a boost of 1000 cGy/5 fractions/1 week in those patients who achieved response. In the three patients who did not receive radiotherapy, two died during the induction phase, one from grade 4 leukopenia and sepsis and the second from unrelated factors. The third patient had systemic progression of disease during induction chemotherapy. Six patients experienced overall improvement in their chemotherapy response from the radiotherapy. Two patients who did not respond to the chemotherapy achieved partial response with irradiation. Four patients who had partial response to the chemotherapy achieved complete response with irradiation, and seven patients had no further change in their degree of response to irradiation. The overall median survival of this group was 81 weeks. Maintenance chemotherapy was not given. After radiotherapy, the site of first failure was outside the radiation field in nine of 13 patients (69%). Hematologic toxicity was dose-limiting. Other toxic effects that were not dose-limiting included nephrotoxicity, neurotoxicity, and acute nausea and vomiting. In the patients with advanced regional disease, there was no increase in the radiation toxicity attributable to the chemotherapy. We conclude that: (a) this dose schedule of vinblastine and cisplatin has reproducible activity in non-small cell carcinoma of the lung; (b) the response and median survival of patients with advanced regional disease are superior to those of patients with metastatic disease; and (c) in patients with advanced regional disease, treatment with chemotherapy followed by radiotherapy yielded an overall response rate of 81% (90% confidence interval of true response, 60%-93%) and improved survival compared to a similar group of patients studied by others receiving radiotherapy alone. We recommend further testing of this concept.
 ...
PMID:Cisplatin and vinblastine chemotherapy for metastatic non-small cell carcinoma followed by irradiation in patients with regional disease. 395 44

Eighteen patients with advanced malignancies refractory to other forms of treatment were given dactinomycin (Act D) as continuous intravenous infusions. Their median age was 51 years (range, 36-67); their median performance status was 50 (range, 40-90) on the Karnofsky scale. Act D was administered continuously for 5 days, utilizing a central venous line and a perfusion pump. The starting dose was 0.1 mg/m2/24 hours X 5 days (total dose, 0.5 mg/m2) and was escalated according to a modified Fibonacci scale to 0.2, 0.33, and 0.5 mg/m2/24 hours X 5 days, respectively. Three, three, four, and eight patients were entered, respectively, in each dose level. Toxicities observed were: leukopenia in four patients (nadir leukocyte count less than 1000 cells/nm3 in one patient and 2000-3000 cells/mm3 in 3 patients); thrombocytopenia, with nadir platelet counts between 50,000 and 100,000 platelets/mm3 in 2 patients; stomatitis in four patients; and nausea in three patients. Vomiting was not observed during the infusions. Two patients may have had a radiation recall phenomenon. Blood count depression, nausea, and mucositis were transient, resolving after a few days. One patient at level IV died of sepsis, which was diagnosed on the fourth day of the infusion, before leukopenia intervened. No objective responses were seen. It was concluded that a higher dose of Act D can be given by continuous infusion than by a bolus injection; the authors recommended 0.5 mg/m2/day X 5 days (total dose, 2.5 mg/m2) for further studies.
 ...
PMID:A phase I trial of dactinomycin intravenous infusion in patients with advanced malignancies. 400 96

Among 31 consecutive patients who developed acute nonlymphocytic leukemia following treatment with chemotherapy or radiation therapy, 17 were treated with intensive chemotherapy aimed at inducing a complete remission. Seven of these 17 patients (41%) obtained a complete remission that ranged in duration from 2 to 11 (median 3) months. Two additional patients who failed to develop normal peripheral blood counts despite postinduction bone marrows that were normocellular and free of leukemia were classified as nonresponders. The median time to complete remission and median duration of leukopenia (WBC less than 1,000/mu 1) were 34 days and 23 days, respectively. Induction chemotherapy was complicated by fever in all patients, documented infection in six patients, and death secondary to sepsis in three. Survival of the 17 patients ranged from less than 1 to 39 (median 4) months. Patients achieving a complete remission had a median survival time of 10 months compared to 2 months for the nonresponders. The other 14 patients received only supportive care and had a median survival of 2 months. These findings indicate that therapy-associated acute nonlymphocytic leukemia (t-ANLL) can frequently respond to chemotherapy and that achieving a complete remission is associated with longer survival. Although these results are encouraging, patients with t-ANLL still have a relatively poor prognosis and efforts directed at improving treatment outcome need to be continued.
 ...
PMID:Response of therapy-associated acute nonlymphocytic leukemia to intensive induction chemotherapy. 401 Jun 22

Pneumococcal bacteremia is associated with a high morbidity and mortality, especially when leukopenia is present. To define further the possible factors associated with death in pneumococcal bacteremia, we reviewed all cases at 2 hospitals over a 1-yr period. Overall, increased mortality was associated with women (p = 0.009), nosocomial acquisition of the disease (p = 0.001), the presence of leukopenia (p = 0.00002) or thrombocytopenia (p = 0.025), shock (p = 4 X 10(-8)), and adult respiratory distress syndrome (p = 2 X 10(-7)). Leukopenic and nonleukopenic patients were compared further to ascertain factors that may predispose to leukopenia. Alcoholism was the only associated condition correlating with the presence of leukopenia (p = 0.036), and alcoholism and leukopenia occurred in a group of younger men. We conclude that the association of alcoholism, leukopenia, and pneumococcal sepsis is a distinct clinical entity seen in younger patients and is associated with a very high mortality.
 ...
PMID:Alcoholism, leukopenia, and pneumococcal sepsis. 405 12


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>