Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of the study was to evaluate the toxicity and biological activity of highly purified lipopolysaccharide (LPS) administered intravenously to cancer patients in order to establish an optimum dosage scheme. An initial subtoxic dose was increased in weekly increments in accordance with individual regimens that maintained patient reaction at a safe and acceptable level. Purified LPS from Salmonella abortus equi was administered to 11 patients with advanced solid tumors on a weekly schedule with intraindividually escalating dosage as determined by patient response. Biological response was monitored by complete blood count, C-reactive protein, and cytokine measurements at different time points after LPS injection. Tumor necrosis factor-alpha (TNF) and interleukin-1 beta serum levels were measured by enzyme-linked immunosorbent assay and interleukin-6 (IL-6) by bioassay. Dose-limiting toxicities including chills and fever (WHO grade III) were reached at 1.0 ng/kg of body weight (maximal tolerated dose-1, MTD-1). Pretreatment with ibuprofen (1,600 mg) abrogated these side effects, allowing further escalation of LPS doses up to 10 ng/kg of body weight. At dose levels greater than 8.0 ng/kg of body weight (MTD-2), the aforementioned side effects occurred again and, additionally, hepatic toxicity (WHO grade III) was observed. Hematological changes included neutropenia followed by a pronounced neutrophilia contributed to by up to 30% bands, marked monocytopenia for 3 h, and retarded lymphopenia. By 24 h, all hematological parameters returned to pretreatment values. TNF serum levels increased from 10 pg/ml before treatment to 7,000 pg/ml as a function of dosage. Maximum serum levels were reached at 60 to 90 min after LPS injection. Similarly, IL-6 serum concentrations increased from less than 4 to 2,500 U/ml; peak levels were obtained 30 min after TNF peak values. Prior administration of ibuprofen had no effect on the above-mentioned hematological changes nor on cytokine release. LPS can be administered intravenously in weekly intervals at escalating doses from 0.15-10.0 ng/kg of body weight, when patients are protected by pretreatment with ibuprofen at dose levels above 1.0 ng/kg of body weight. Cytokine release as measured by TNF and IL-6 increased in a dose-dependent manner although the constitutional symptoms are completely attenuated.
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PMID:Biological response to intravenously administered endotoxin in patients with advanced cancer. 225 60

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.
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PMID:Response of C-reactive protein in neonatal Group B streptococcal infection. 388 78

No single diagnostic test for neonatal sepsis is both rapid and reliable. Combining leukocyte (wbc) counts with acute phase reactants (APR) enhances diagnostic accuracy. The most helpful wbc counts are leukopenia (less than 5.0 x 10(9)/l), increased immature/total neutrophils (greater than or equal to 0.2) and profound neutropenia (less than 1.0 x 10(9)). Of the APR, C-reactive protein responds most rapidly, but alpha 1-acid glycoprotein (orosomucoid), haptoglobin and mini-ESR (greater than or equal to 15 mm/h) are also useful. Rapid, quantitative determinations of APR are now available with nephelometric techniques. Abnormal wbc counts frequently appear before APR changes in group B streptococcal infection. Sequential determinations of wbc counts and APR may provide valuable diagnostic and prognostic information.
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PMID:White blood cells and acute phase reactants in neonatal sepsis. 608 34

Seventy-four patients with rheumatoid arthritis were treated with sulphasalazine. There was a significant improvement in clinical score, with substantial falls in serum C-reactive protein concentrations and erythrocyte sedimentation rate four weeks after starting the drug. Improvement was maintained in the 38 patients who remained on the drug for one year. The mean Rose-Waaler titre did not change. There was little difference between the results in seropositive and seronegative patients. The commonest adverse effect was dyspepsia, but five patients developed a megaloblastic anaemia and one patient neutropenia; all made a complete recovery. The results suggest that the drug has a disease-modifying action not attributable to its "salicylate" content. The mode of action might be by an antibacterial effect on gut flora.
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PMID:Sulphasalazine in rheumatoid arthritis. 610 77

C-reactive protein (CRP) was measured serially in 29 patients with acute leukaemia. Sixty-four febrile episodes (greater than or equal to 38 degrees C) occurred during 37 periods of neutropenia (less than 0.5 X 10(9)/l). In all of 41 microbiologically or clinically documented infections the maximum CRP level exceeded 30 mg/l, and in 25 it was greater than 100 mg/l. In no case in which the CRP level remained below 30 mg/l for 48 hr after the onset of fever was any clinical or microbiological evidence of infection obtained. The CRP level during documented infection began to fall 24-48 hr after appropriate treatment was begun. A CRP level above 30 mg/l in neutropenic patients was associated with early recurrence of fever if systemic antibiotics were discontinued. Graft-vs-host disease, without infection, did not result in high levels of CRP.
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PMID:Serum C-reactive protein levels in the management of infection in acute leukaemia. 658 11

A total of 1,622 daily measurements of the level of C-reactive protein (CRP) in the serum of 40 hospitalized patients with neutropenia were made during 55 study periods from October 1990 through February 1993 (mean, 29.5 measurements per period). Clinical events were categorized into four groups: group I (bloodstream infection), group II (significant bacterial or fungal infection without bloodstream infection), group III (fever without an obvious source), and group IV (drug-related fever). There was a strong association between baseline elevation of the CRP level (> or = 100 mg/L) and tumor-associated fever (P = .0005); the resolution of such fever coincided with a decrease in the CRP level following chemotherapy. Levels of CRP increased by > or = 40 mg/L in 10 (31%) of 32 cases during the 48-72 hours preceding the clinical diagnosis of a subsequently demonstrable infection--often pneumonia without bloodstream infection. CRP values on day 2 (1 day after the diagnosis of a clinical event) were significantly higher for events in groups I and II than for those in group III (P < .01) but not those in group IV. With regard to significant infections, a day-2 CRP value of > or = 40 mg/L was 100% sensitive and an increase in CRP level of > or = 50 mg/L from day 1 to day 2 had a positive predictive value of 95%. We conclude that serial measurements of serum CRP levels may be helpful in determining the extent of evaluation required for a newly febrile neutropenic patient and possibly in accelerating the detection of an otherwise unsuspected infection.
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PMID:A prospective study of daily measurement of C-reactive protein in serum of adults with neutropenia. 757 19

In patients with advanced multiple myeloma (MM) there is an excess of production of interleukin-6 (IL-6) in vivo, and elevated serum levels are associated with plasmablastic proliferative activity and short survival. These data prompted us to perform a clinical trial with a murine anti-IL-6 monoclonal antibody (MoAb) to neutralize the excess of this putatively deleterious factor in these patients. Ten MM patients with extramedullary involvement frequently were treated with anti-IL-6 MoAb. The MoAb was administered intravenously to 9 patients; 1 patient with malignant pleural effusion received intrapleural therapy. Of the 3 patients who succumbed to progressive MM after less than 1 week of treatment (including the only 1 treated locally), 2 with evaluable data exhibited marked inhibition of plasmablastic proliferation. Among the 7 patients remaining more homogeneous receiving the anti-IL-6 MoAb for more than 1 week, 3 had objective antiproliferative effect marked by a significant reduction of the myeloma cell labelling index within the bone marrow. One of these 3 patients achieved a 30% regression of tumor mass. However, none of the patients studied achieved remission or improved outcome as judged by standard clinical criteria. Of major interest, objective antiproliferative effects were associated with complete inhibition of C-reactive protein (CRP) synthesis and low daily IL-6 production in vivo. On the other hand, the lack of effect in 4 patients was associated with a higher IL-6 production and inability of the MoAb to neutralize it. Anti-IL-6 was also associated with resolution of low-grade fever in all the patients and with worsening thrombocytopenia and mild neutropenia. The generation of human antibodies to Fc fragment of the murine anti-IL-6 MoAb observed in 1 patient was associated with dramatic progression. These data show that anti-IL-6 MoAb can suppress the proliferation of myeloma cells and underscore the biologic role of IL-6 for myeloma growth in vivo. Furthermore, suppression of CRP and worsening of neutropenia/thrombocytopenia both indicate that IL-6 is critically involved in acute-phase responses and granulopoiesis/thrombopoiesis.
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PMID:Biologic effects of anti-interleukin-6 murine monoclonal antibody in advanced multiple myeloma. 760 99

A phase IIb trial using liposome-encapsulated muramyl tripeptide phosphatidylethanolamine (L-MTP-PE) in combination with ifosfamide (IFX) for patients with relapsed osteosarcoma was undertaken to determine (a) the tolerability of the combination therapy, (b) if L-MTP-PE increased the toxicity of IFX, and (c) whether IFX altered or suppressed the in vivo immune response to L-MTP-PE. Patients had histologically proven osteosarcoma and pulmonary metastases that either developed during adjuvant chemotherapy or were present at diagnosis, persisted despite chemotherapy, and recurred following surgical excision. Stratum A patients were rendered clinically free of disease within 4 weeks of study entry prior to receiving combination therapy. IFX was administered at 1.8 g/m2 for 5 days every 21 days for up to eight cycles. L-MTP-PE was administered twice weekly for 12 weeks, then once weekly for 12 weeks. Once cycle of combination therapy was defined as 5 days of IFX and 3 weeks of L-MTP-PE therapy. Stratum B patients had measurable disease at study entry that was judged to be amenable to surgical resection. Stratum B patients received three cycles of combination therapy prior to surgery to judge clinical and histologic response. Postoperatively, patients received an additional five cycles. A total of nine patients were entered into the protocol: six on stratum A and three on stratum B. Serial blood samples were collected and assayed for cytokine levels (tumor necrosis factor-alpha [TNF alpha], interleukin-6 [IL-6], IL-8, neopterin, C-reactive protein). In addition, peripheral blood monocyte tumoricidal activity was evaluated pre- and post-combination therapy. Complete blood counts with differential and platelet counts were followed weekly. No increase in the toxic side effects of IFX was demonstrated when administered with L-MTP-PE nor were delays in IFX administration due to neutropenia experienced. The toxic side effects of L-MTP-PE were also not increased. Elevations of serum C-reactive protein, plasma neopterin, IL-6, IL-8, and TNF alpha following combination therapy were similar to those observed in patients treated with L-MTP-PE alone. Monocyte-mediated tumoricidal activity was elevated 24 and 72 h following L-MTP-PE and IFX therapy, similar to what has been reported following L-MTP-PE alone. Tumor specimens obtained from stratum B patients showed the histologic characteristics consistent with a "chemotherapy effect," i.e., dead, amorphous, acellular osteoid with cell drop-out.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Combination therapy with ifosfamide and liposome-encapsulated muramyl tripeptide: tolerability, toxicity, and immune stimulation. 761 44

In the present study a new technique for measuring the erythrocyte sedimentation rate (ESR) is clinically evaluated. This technique extends the measuring range above that of the traditional ESR by calculating the sedimentation (S) at 60 minutes from data collected between 18 and 24 minutes. Measurement of ESR, S and C-reactive protein (CRP) was performed prospectively three times a week in 25 patients developing 30 fever episodes following chemotherapy for a hematological malignancy. A good correlation was obtained between S and ESR values up to 90 mm (r = 0.98; p < 0.0001). The use of S may allow the clinician to follow an infectious or inflammatory process more accurately than with ESR. During neutropenia a rise in S preceded fever in all episodes were two samples were obtained before start of fever (n = 13). Changes in CRP and S values showed the same pattern in 11 episodes, in 12 CRP preceded S and in 7 episodes there was no correlation between the results. CRP, opposed to S, discriminated between bacteremias and blood culture negative episodes (p < 0.05) in samples obtained during the first 72 hours after start of fever. In patients with fever during neutropenia determination of S does not offer any clear advantage to CRP.
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PMID:Use of a novel measuring technique for the erythrocyte sedimentation rate--a pilot study in patients with neutropenia and fever. 771 31

Serum endotoxin, interleukin-6 (IL-6) and C-reactive protein (CRP) were serially determined in 26 patients with hematological malignancies and chemotherapy-induced neutropenia who developed fever. Endotoxin in serum was detected in 69% of the patients, with the highest values being recorded in patients with gram-negative (Gr-) bacteremia. High levels of IL-6 were found after start of fever, and in 6/9 patients with Gr- bacteremia levels exceeded 200 ng/l in samples drawn within the first 72 hours. However, only in 2/17 patients with gram-positive bacteremias and blood culture-negative fever episodes did IL-6 exceed this concentration (p < 0.05). High CRP values (exceeding 100 mg/l) did not discriminate between Gr- and non-Gr- episodes (7/9 versus 10/17, respectively). In patients with fever at day 3-5 (n = 15), IL-6 values > 100 ng/l were associated with fever continuing for more than 7 days after start of the episode; contrarily, CRP values did not indicate the persistence of fever. Determination of IL-6 may be a better test than CRP in monitoring the acute response to infection in the neutropenic patient. A combination of high endotoxin and IL-6 values may indicate a Gr- bacteremia. This could have therapeutic implications before results of blood cultures are obtained.
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PMID:Monitoring of endotoxin, interleukin-6 and C-reactive protein serum concentrations in neutropenic patients with fever. 778 67


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