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

Doxifluridine, a new fluorouracil analog with a low myelosuppressive effect, has recently been subject to various disease-oriented, Phase II trials. For the present evaluation of drug tolerance, the Phase II data of 114 patients having received 376 doxifluridine cycles has been used. The treatment cycles consisted of 5 daily intravenous injections of 4,000 mg/m2 non-pretreated patients, and 3,000 mg/m2 in pretreated patients. Previous observations showing that doxifluridine is less myelotoxic than fluorouracil have been confirmed. 54% of the patients had no leucopenia (maintaining WBC counts over 3,000/mm3 and 90% had no thrombopenia (platelets not lower than 100,000/mm3) throughout treatment. However, a WHO grade 4 hematologic toxicity was observed in 9 patients, and 2 toxic deaths were related to severe granulocytopenia and sepsis. Digestive tract toxicity was similar and equally frequent as the one observed with fluorouracil: mucositis with oral ulcerations (19%), nausea and vomiting requiring specific treatment (8%) and severe but never hemorrhagic diarrhoea (5%). Neurologic toxicity was frequent, with 20% of patients complaining of somnolence and/or peripheral neuropathy, 7% of impaired consciousness and 1% of WHO grade 4 cerebellar ataxia. Among the 10% of patients with cardiac symptoms, 6% were benign and transient arrhythmias, and 4% were severe, including 1 myocardial infarction, 1 spontaneously reversible cardiac arrest and 2 ventricular fibrillations successfully treated with cardioversion. In spite of its encouraging antitumor activity and its good hematologic tolerance, intravenous doxifluridine, as used in this study, cannot be recommended because of the observed neurologic and cardiac toxicity. Oral doxifluridine is presently under investigation with preliminary results suggesting a lack of neuro- or cardiotoxicity.
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PMID:[Doxifluridine toxicity, a fluorouracil analog with low myelosuppressive effect]. 214 Feb 80

Of 19 patients with advanced transitional bladder cancer (T2-T4, N0-N+, M0) who received two or three cycles of pre-emptive MVC (Methotrexate, Vinblastine, Cisplatin), pathological partial (PR) and complete (CR) remissions were observed in 67% (50% and 17% respectively). The toxicity of chemotherapy was generally acceptable but 5 patients required hospitalization for neutropenia and thrombopenia . In one of them chemotherapy was stopped for severe sepsis. No death was observed. In 11 patients follow-up is greater than 12 months. In this group, 10 patients are actually alive and disease-free, while the other one was dead owing to brain metastasis, after eight months from surgery.
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PMID:[Neoadjuvant chemotherapy with MVC (methotrexate, vinblastine, cisplatin)in the treatment of infiltrating transitional carcinoma of the bladder]. 214 7

"Postoperative erythroderma", the pathogenesis of this disease have solved as graft-versus-host disease (GVHD) due to blood transfusion, is fatal and impossible to cure for the time being. Therefore the prevention against the disease is very important. One woman and three men who underwent an operation and blood transfusion at our department died of this disease. They fell into high fever on 11-13 days, erythroderma on 12-16 days, liver dysfunction on 14 days, and leukocytopenia on 17-19 days, after surgery and transfusion. Eventually, they all suffered from thrombocytopenia, diarrhea, renal dysfunction, and sepsis which led to death. The clinical course, macroscopic and microscopic findings of them coincided with those of GVHD. Since 1989, we have tried following methods for prevention of postoperative erythroderma: Reducing blood transfusion, especially fresh blood and fresh thrombocyte plasma, by using predeposited autologous blood, autologous washed erythrocytes collected from the operative area before and after extracorporeal circulation (ECC), concentrated residual blood from the ECC using a hemoconcentrater, and 1,500 rad of cobalt-irradiation of fresh blood, fresh thrombocyte plasma, and blood collected within 7 days prior to the transfusion. Postoperative erythroderma has not been experienced by introduction of these methods since 1989.
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PMID:[Studies on so-called "postoperative erythroderma": report of four cases]. 214 58

Aspiration or ingestion of contaminated amniotic fluid or vaginal secretions has been suggested as a cause of systemic group B streptococcal (GBS) infection in the neonate. Suckling rat studies disagree on whether systemic disease will develop after an oral challenge of GBS. Our goal was to determine if systemic GBS disease would occur following oral colonization in the suckling rat and the effect of bacterial, host and environmental factors. Suckling rat littermates received oral inoculation on one of the first four days of life with varying doses and strains of GBS. Studies confirmed gastric inoculation without aspiration. Mortality and bacteremia decreased with age, increased with dose, varied with strain, and increased with asphyxia. Autopsy confirmed sepsis, intestinal colonization, meningitis, and pneumonia. Bacteremia was associated with an abnormal immature: total neutrophil ratio at 24 hr, thrombocytopenia at 48 hr, and neutropenia at 72 hr after inoculation. GBS can cause systemic infection in the host after oral colonization which appears age-, dose, strain-, and environment-dependent. Evaluation of GBS entry in the susceptible host may facilitate therapies directed toward preventing mucosal invasion.
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PMID:Systemic group B streptococcal disease in the neonate: characterization of an oral colonization model using the suckling rat. 214 5

We report two cases of adrenal hemorrhage and review 17 others that were confirmed by hormone measurements and computed tomography. Precipitating factors included heparin therapy, surgery, hypotension, and sepsis. Heparin-associated thrombocytopenia may be an underappreciated cause of adrenal hemorrhage. Despite the availability of computed tomography, adrenal hemorrhage mimics many other diseases, and an early diagnosis remains difficult.
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PMID:Adrenal insufficiency secondary to adrenal hemorrhage. Two case reports and a review of cases confirmed by computed tomography. 218 38

Pharmacokinetics and clinical study of aztreonam (AZT) in neonates and premature infants were conducted with the following results: 1. Pharmacokinetics (1) Serum concentrations of AZT at 30 minutes after one-shot intravenous injection of 10 mg/kg and 20 mg/kg to neonates including premature infants were 20.6-26.6 micrograms/ml and 38.5-46.4 micrograms/ml, respectively, and decreased thereafter. A dose response was observed in the serum concentrations with administration of AZT 10 mg/kg and 20 mg/kg. (2) Serum half-lives (T1/2) tended to be shorter in both mature and premature infants as their day-ages increased and T1/2 tended to be prolonged in premature infants compared with mature infants. (3) Changes in serum concentration upon one-hour intravenous drip infusion of AZT 20 mg/kg were very similar to those upon one-shot intravenous injection. (4) Urinary excretions in the first 6 hours after one-shot intravenous injection of AZT 10 mg/kg or 20 mg/kg tended to increase in mature infants as they grew and showed excretion rate of 26.2-54.3% but those in premature infants did not show any specific tendency with rate of 17.5-45.1%. Urinary excretions upon intravenous drip-infusion showed a tendency very similar to those upon intravenous injection. 2. Clinical studies (1) Clinically evaluable cases of AZT treatment were 88 cases (91 diseases), in which pathogenic organisms were identified in 56 cases (Group A), i.e., sepsis 9, purulent meningitis 2, pneumonia 8, urinary tract infection (UTI) 33 and others. Total efficacy rate was 98.2% including "excellent" (39), "good" (16) and "fair" (1). Number of cases in which pathogenic organisms were unknown (Group B) was 11, i.e., suspected sepsis (4), pneumonia (3) and intrauterine infection (4) and the efficacy rate was 100% with "excellent" (4) and "good" (7). Thus, both group A and B showed excellent results. AZT was also given to 24 cases for prophylaxis and all the cases showed prophylactic effect of AZT.4+ Bacteriologically AZT was deemed effective in 53 cases out of 56 (Group A) with identified pathogens "eradicated" and "unchanged" (2), thus the bacterial eradication rate was 96.2%. (3) A minor degree of loose feces was observed in 1 (1.3%) of 80 cases as a side effect. Abnormal laboratory test values found were eosinophilia (3 cases), elevation of GOT and GPT (2), platelet-increase (1), elevation of GOT (1), and thrombocytopenia.elevation of GOT.GPT.LDH (1). Every one of these was of a minor degree and transient. From the above pharmacokinetics and clinical results, standard dosage of AZT to neonates and premature infants should be in a unit dose of 20 mg/kg, twice daily to those with ages between 0 and 3 days, and 2 to 3 times daily to those with ages 4 days and above, by intravenous injection or intravenous drip infusion.
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PMID:[Pharmacokinetics and clinical studies on aztreonam in neonates and premature infants (the first report). Study on effectiveness and safety in mono-therapy with aztreonam. A study of aztreonam in the Perinatal Co-research Group]. 219 68

We conducted a prospective, randomized trial to study the efficacy and tolerance of long-term versus short-term treatment with recombinant interferon alfa-2a in patients with chronic hepatitis B. Ten patients were randomly assigned to a 6-month interferon regimen, and 10 patients were assigned to a 3-week interferon trial. Eleven patients (five assigned to long-term treatment and six to short-term treatment) did not complete interferon therapy: eight had either severe thrombocytopenia or neutropenia; one had pronounced fatigue in relationship to administration of interferon; one had spontaneous bacterial peritonitis and sepsis and died; and one had a massive fatal variceal hemorrhage during interferon therapy. Most of the serious hematologic complications occurred in patients with cirrhosis and hypersplenism. In one patient, seroconversion to hepatitis B virus DNA negativity occurred before the onset of treatment. Four of the five patients able to complete the 6-month interferon regimen and only one of four patients able to complete the 3-week trial had seroconversion to hepatitis B virus DNA negativity. Thus, we conclude that the therapeutic response was better among patients who were able to complete a 6-month interferon trial. In patients with cirrhosis and hypersplenism, development of either severe thrombocytopenia or leukopenia associated with interferon therapy precluded completion of treatment.
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PMID:Long-term versus short-term treatment with recombinant interferon alfa-2a in patients with chronic hepatitis B: a prospective, randomized treatment trial. 221 80

Ten previously untreated patients with gastric cancer were treated with etoposide, 120 mg/m2 intravenously (i.v.) on days 4, 5, and 6, Adriamycin, 20 mg/m2 i.v. on days 1 and 7, and cisplatin, 40 mg/m2 i.v. on days 2 and 8 (EAP). Etoposide, 240 mg/m2 on days 4, 5, and 6, was administered orally instead of intravenously in alternating cycles, and pharmacokinetic studies were performed in those who had previously undergone gastrectomy or who had tumor infiltrating the stomach to determine oral bioavailability. Nine patients had advanced measurable gastric cancer, and one patient had an elevated carcinoembryonic antigen after surgery for synchronous gastric and colon cancer. The median age was 54 years (range 38-69), and the median Eastern Cooperative Oncology Group (ECOG) performance status was 2 (range 0-3). Nine of 10 patients had poorly differentiated adenocarcinoma. Twenty-four cycles were administered to 10 patients, and hematologic data were available for 23 courses. ECOG grade 4 neutropenia and thrombocytopenia developed in 19 (83%) and 8 (53%) courses, respectively. Thirteen courses (54%) were complicated by fever requiring parenteral antibiotics. Two patients (20%) died due to neutropenic sepsis. The profound myelotoxicity observed in our study prompted us to terminate the investigation prior to completing accrual. The oral bioavailability of etoposide was 21% and 36% in the two patients who had had prior gastrectomy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Phase II trial of etoposide, doxorubicin (Adriamycin), and cisplatin (EAP regimen) in advanced gastric cancer. 222 Jun 57

Previously we studied levels of the cytokine IL-6 and activation of the complement and contact system and of neutrophils in a group of 48 patients with sepsis. Some of these inflammatory parameters appeared to be associated with a poor prognosis. Here we report on the relationships of C4a and C3a (complement activation products), of factor XII and prekallikrein (contact system proteins), of elastase (a protease released by activated neutrophils) and of the cytokine IL-6 to hemodynamic and biochemical parameters measured in those 48 patients at the time of admission to the Intensive Care Unit. No significant correlations between any inflammatory parameter and either systemic vascular resistance or cardiac index were found. Mean arterial pressure significantly correlated with both factor XII and prekallikrein levels. Lactate correlated with C3a and C4a, with elastase, and in particular, with IL-6, whereas it did not correlate with either factor XII or prekallikrein. Platelet numbers inversely correlated with both C3a and C4a, as well as with elastase and IL-6, whereas they positively correlated with factor XII and prekallikrein. Based on these findings we propose a model for the interplay of these inflammatory mediators in the pathogenesis of sepsis. This model takes into consideration the occurrence of capillary leakage, shock, disseminated intravascular coagulation, thrombocytopenia and of acute phase reactions in sepsis.
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PMID:A model for the interplay of inflammatory mediators in sepsis--a study in 48 patients. 228 88

A 54-year-old woman with a 19-year history of rheumatoid arthritis developed life-threatening thrombocytopenia one week after beginning butoconazole therapy for a vaginal yeast infection. This was complicated by upper gastrointestinal hemorrhage that probably resulted from ibuprofen and methotrexate therapy. Sepsis, myelophthisic anemias, and other potential etiologies were ruled out. Once stabilized, the patient was rechallenged with other medications without incident. These findings indicate that a potentially serious thrombocytopenia may result from the administration of butoconazole vaginal cream or in combination with methotrexate and/or ibuprofen.
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PMID:Severe reversible thrombocytopenia resulting from butoconazole cream. 230 9


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