Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Eighteen cases of alloimmune neonatal neutropenia (ANN) were analysed for their clinical and serological properties. Pregnancy was normal in all cases, but a 50% incidence of abortion is recorded. With the exception of two premature babies, all newborns were delivered at term. Omphalitis and mild infections of the skin were predominantly present. None of the new-borns died by overwhelming sepsis. The average duration of neutropenia was 11 weeks (range 3-28 weeks). Intravenous IgG therapy was followed by transient remission in 2 of 4 affected newborns. Antibody differentiation revealed in five sera NA1-, in four sera NA2- and in two sera NB1-specific antibodies. In two sera only HLA antibodies were detectable. Complement activating antibodies were determined in 72% of the sera. Screening for granulocyte-specific antibodies in 1016 postpartum sera of unselected women revealed a total of 11 sera (1.1%) reacting selectively with granulocytes, but only four (0.4%) were directed against a known granulocyte-specific antigen. None of the new-born of mothers alloimmunized to granulocyte antigens developed neutropenia, which suggests an incidence of ANN below 0.1%.
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PMID:Serological and clinical aspects of granulocyte antibodies leading to alloimmune neonatal neutropenia. 128 78

In an attempt to identify risk factors for Staphylococcus aureus septicemia, 136 consecutive HIV-infected patients were investigated for the presence of nasopharyngeal colonization with Staphylococcus aureus and subsequent Staphylococcus aureus infection. Sixty of 136 (44.1%) HIV-infected patients had staphylococci which were detected in the nasopharynx on initial culture compared to 12 of 39 (30.8%) patients with chronic diseases and 11 of 47 (23.4%) healthy hospital staff. Another 12 HIV-infected subjects proved to be Staphylococcus aureus carriers on follow-up cultures. Patients with full-blown AIDS had a higher carriage rate compared to subjects who were only HIV-positive (p < 0.05), indicating that Staphylococcus aureus colonized patients were more severely ill. Eight patients with Staphylococcus aureus septicemia were observed, all of whom were carriers; no septicemia occurred in the non-colonized patients (p < 0.01). Colonized patients with neutropenia (< 1000/microliters) were significantly more likely to develop septicemia (p < 0.01). Nasopharyngeal colonization with Staphylococcus aureus and the presence of an indwelling catheter were established to be factors that help identify patients at risk of acquiring subsequent Staphylococcus aureus infection.
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PMID:Association between Staphylococcus aureus nasopharyngeal colonization and septicemia in patients infected with the human immunodeficiency virus. 129 67

We have treated sixty-two patients (21 with limited disease, 41 with extensive disease), on an outpatient-basis schedule of six drugs administered weekly for twelve weeks. Cyclophosphamide, 400 mg/m2, adriamycin, 20 mg/m2 and vincristine, 2 mg, full dose, were administered during weeks 1, 5 and 9; cisplatin, 50 mg/m2 and etoposide, 100 mg/m2 during weeks 2, 6 and 10; adriamycin and vincristine at the same doses during weeks 3, 7 and 11; methotrexate 30 mg/m2, during weeks 4, 8 and 12. After the first 28 patients vincristine was replaced by teniposide (VM-26) due to neurotoxicity. The overall response rate was 64.5% (complete remission 13 p., partial remission 27 p.). Toxicity grade 3-4, mainly nausea and vomiting or neutropenia, was recorded in 17 patients. Alopecia grade 1-2 was universal. One toxic death occurred from sepsis. The overall survival was 8 months (range 1-40), (95% CL: 53-77%); 8 months in limited disease (range 1-40), and 7 months in extensive disease (range 1-23). Time to treatment failure was 6 months (7 limited disease, 5 extensive disease). In conclusion, the results of this alternating schedule are poorer than those attained with standard, high-dose treatments, mainly in limited disease, but could be a less toxic option for patients with extensive disease.
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PMID:Alternating chemotherapy for small-cell lung cancer. A twelve-week schedule of six drugs. 131 40

Between July 1986 and February 1991, 10 patients with small cell carcinoma of the cervix were prospectively treated with combination chemotherapy using cisplatin (50 mg/m2) and doxorubicin (50 mg/m2) on Day 1 and etoposide (75 mg/m2) on Days 1-3. All patients underwent an extensive pretreatment metastatic survey and had histologic confirmation of small cell carcinoma prior to entry in the study. Seven patients had stage Ib, 1 stage IIa, and 2 stage IIb. Nine patients received chemotherapy at primary presentation and 1 was treated for recurrent disease. In 6 cases, chemotherapy was given and then followed by radiation therapy. Three patients received chemotherapy following radical hysterectomy and 1 was treated for persistent disease after radiation therapy. Patients received a median of four courses of chemotherapy (range 2-6). Neutropenia was the dose-limiting toxicity with 9 of 10 patients requiring a dose reduction. There was no instance of neutropenic sepsis or other major toxicity. Seven patients had measurable disease at the start of therapy. Three of these patients had a complete clinical response, 1 had a partial response, 2 had stable disease, and 1 had progressive disease (response rate = 57%). The median survival was 28 months. At the time of this report, 4 of 6 patients with stage Ib cancers given primary treatment on this regimen remained free of disease (with 28 months the median follow-up). Our pilot study indicates that this chemotherapy regimen has activity in small cell carcinoma of the cervix and should be further evaluated as an adjuvant to surgery or radiation in patients with early stage disease.
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PMID:Treatment of small cell carcinoma of the cervix with cisplatin, doxorubicin, and etoposide. 133 Aug 47

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

Neutropenia was seen in rats made septic by subcutaneous (sc) injection of Escherichia coli. The sepsis-induced increase in glucose uptake by tissues distant from the site of infection was not associated with increased myeloperoxidase (MPO) activity. Only the skin and muscle at the site of infection demonstrated an increase in both glucose uptake and MPO activity. Granulocyte colony-stimulating factor (G-CSF) attenuated the sepsis-induced decrease in circulating neutrophils. Both glucose uptake and MPO activity of skin and muscle adjacent to the infection site showed a smaller increase in G-CSF treated rats. In contrast, septic rats injected with G-CSF exhibited a greater number of leukocytes and a larger reduction in the number of bacteria in the sc lavage fluid. These results demonstrate that G-CSF is a potent immunomodulator that stimulates neutrophil function and also increases their recruitment to the site of infection, resulting in improved bacterial killing and host defense.
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PMID:Effect of granulocyte colony-stimulating factor on sepsis-induced changes in neutrophil accumulation and organ glucose uptake. 137 72

Newborns are predisposed to neutropenia and thrombocytopenia during bacterial sepsis. The presence of peripheral cytopenias during overwhelming infection may be secondary to decreased hematopoietic growth factor production during states of increased demand. We therefore examined circulating levels of granulocyte-colony stimulating factor (G-CSF) and IL-3, production of G-CSF and IL-3 from unstimulated and stimulated mononuclear cells (MNC), expression of G-CSF and IL-3 genes during unstimulated and stimulated conditions, and equilibrium and binding of G-CSF receptors on mature effector peripheral blood cells of adults and neonates. Serum from cord and adult peripheral blood contained negligible amounts of both G-CSF (less than or equal to 50 pg/mL) and IL-3 (less than or equal to 5 pg/mL). Constitutive supernatant levels of G-CSF and IL-3 from cord and adult unstimulated MNC were also undetectable. However, there was a significant difference in G-CSF and IL-3 production from stimulated cord and adult MNC. Supernatants from stimulated adult MNC had significantly more G-CSF (p less than 0.007) and IL-3 (p less than 0.02). Additionally, Northern blot hybridization and densitometry of autoradiographs demonstrated significantly more G-CSF and IL-3 mRNA transcripts from adult than from cord MNC. Lastly, affinity, binding, and number of G-CSF receptors on cord and adult peripheral effector cells were equal. These data suggest that, during states of increased demand, cord MNC produce less G-CSF and IL-3 than do adult MNC and have an associated reduction in their respective mRNA transcripts. These findings may have implications in the pathogenesis of neonatal cytopenias during states of increased demand, such as sepsis.
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PMID:Decreased G-CSF and IL-3 production and gene expression from mononuclear cells of newborn infants. 137 59

Forty-nine previously untreated adult patients with diffuse non-Hodgkin's lymphoma were treated with MACOP-B (methotrexate, adriamycin, cyclophosphamide, vincristine, prednisolone and bleomycin) between December 1986 and December 1990. Forty patients (82%) achieved a complete response (CR), three (6%) a partial response (PR), while four (8%) had either no response or progression of disease, one (2%) patient ceased MACOP-B therapy and received other chemotherapy because of sustained neutropenia, and one patient (2%) died of sepsis during therapy. The factors that adversely affected the CR rate were by stage IV, the presence of B symptoms, the presence of a large mass (greater than 5 cm), and low serum total protein level. The 4-year survival for all 49 patients was 70% and the 4-year disease-free survival (DFS) for the 40 CR patients was 77%. Relapses were higher in patients whose initial serum lactic dehydrogenase (LDH) level was higher than 660 IU/1 (DSF 89% vs. 49%). Toxicity was substantial but acceptable, with neutropenia and mucositis proving to be the most frequent severe side-effects. These preliminary results confirmed the effectiveness of MACOP-B therapy for diffuse non-Hodgkin's lymphoma.
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PMID:Treatment of diffuse non-Hodgkin's lymphoma with combined chemotherapy using methotrexate, adriamycin, cyclophosphamide, vincristine, prednisolone and bleomycin (MACOP-B). 138 63

Twenty-six patients with advanced renal cell carcinoma were treated with suramin administered by continuous infusion, with dosing determined by a nomogram. One patient achieved a partial response and five patients achieved a minor response or had stable disease for > 3 months. Toxicities included an immune-mediated thrombocytopenia in one patient and Staphylococcus sepsis that was not associated with neutropenia in five patients. Pharmacokinetic parameters were determined by the ADAPT II MAP-Bayesian parameter estimation program. Patient data were fit using a two-compartment open model and first-order rate elimination. This showed a wide interpatient variation in time to target level (median, 13.8 days), volume of distribution (median, 15.2 liters/m2), and t1/2-beta (median, 20.6 days). The patients who achieved a partial response, minor response, or stable disease had a slower elimination rate of suramin, compared to patients with progressive disease. Tumor specimens were obtained prior to therapy and were analyzed for the production of five different growth factor-specific RNA transcripts. These included transforming growth factor alpha, acidic fibroblast growth factor, basic fibroblast growth factor, and platelet-derived growth factor types A and B. No difference in the pattern of growth factor expression was seen in tumors of responding and nonresponding patients. Suramin does not have significant antitumor activity in renal cell carcinoma. The wide variability in pharmacokinetics suggests that individual dosing should be used in future trials of suramin for treatment for other malignancies. Pertinent corollary studies of tumor biology and clinical pharmacology should be included whenever possible in clinical trials in patients with renal cell carcinoma.
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PMID:Phase II trial of suramin in patients with advanced renal cell carcinoma: treatment results, pharmacokinetics, and tumor growth factor expression. 139 2

In a prospective study elastase alpha 1-proteinase inhibitor (E alpha 1PI), polymorphonuclear (PMN) count, the immature to total neutrophil count ratio (I/T ratio), and C-reactive protein (CRP) were analysed in 74 patients (76 cases) with neonatal septicaemia at the time of initial clinical symptoms. At that early stage of the disease, 94% of the patients had abnormal values for E alpha 1PI, 71% for I/T ratio, 61% for PMN count, and only 54% for CRP. PMN count was a poor indicator of septicaemia. Neutropenia, present in 26% of all patients, was related to normal E alpha 1PI in only 4 patients. The combined use of E alpha 1 and I/T ratio was the most sensitive indicator. In all patients irrespective of causative bacteria or disease onset at least one of these parameters was elevated. In early-onset septicaemia (n = 31), normal CRP values occurred significantly more often (63%) than in late-onset sepsis (33%). Even in five of the seven fatal cases, initial CRP measurements were normal. The sensitivity of PMN count and I/T ratio did not differ significantly between early- and late-onset septicaemia. Laboratory changes observed in 18 newborns during the first 3 days of the septic episode show that the rate of pathological values for E alpha 1PI and I/T ratio was highest at the time of initial clinical symptoms and decreased on days 2 and 3. In contrast, CRP reached maximal values as late as day 2 (88% abnormal values), followed by a decrease on day 3. We conclude that the use of E alpha 1PI may improve the laboratory detection of neonatal septicaemia especially if used in combination with I/T ratio.
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PMID:Elastase alpha 1 proteinase inhibitor complex, granulocyte count, ratio of immature to total granulocyte count, and C-reactive protein in neonatal septicaemia. 139 90


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