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[Parenteral nutrition: indications and techniques].

Parenteral nutrition corrects for or prevents malnutrition in patients with acute or chronic bowel disease. Whether acute (a few days to a few weeks) or chronic (a few weeks to several years), there are two pathophysiological mechanisms of bowel disease leading to malnutrition: motricity disorders and defective absorption. Total parenteral nutrition has to be prescribed in three situations: occlusive intestinal stenosis, pseudo-obstruction with complete food intolerance, clinically or endoscopically severe colitis. The indication for total parenteral nutrition to allow the intestine to "rest" is indicated in case of digestive fistulae with a high flow and for inflammatory bowel disease (Crohn's disease, irradiated bowel disease). In other cases, parenteral nutrition can be used as a complement to poorly tolerated or quantitatively insufficient oral or enteral nutrition to maintain the patient's nutritional status or correct for malnutrition. Peripheral (<3 weeks) or central (>3 weeks) parenteral nutrition, like all types of nutritional support, must be complete and conducted according to a rigorous written protocol specific for each indication, particularly acute versus chronic intestinal disease, in order to avoid iatrogenic and metabolic risks. This goal can be best achieved by developing a nutritional team within each hospital. Two other important goals are to enhance the efficacy of the nutritional support and to avoid inappropriate prescriptions, notably for parenteral administration. Such an approach allows a better risk/benefit ratio evaluated with nutritional standards. These are the prerequisites for nutritional therapy to be recognized as a major discipline in medicine.

Acute Disease↗

Long term evaluation of etiological treatment of chagas disease with benznidazole.

The aim of this article is to present an investigation of cure rate, after long follow up, of specific chemotherapy with benznidazole in patients with both acute and chronic Chagas disease, applying quantitative conventional serological tests as the base of the criterion of cure. Twenty one patients with the acute form and 113 with one or other of the various chronic clinical forms of the disease were evaluated, after a follow up period of 13 to 21 years, for the acute, and 6 to 18 years, for the chronic patients. The duration of the acute as well as the chronic disease, a condition which influences the results of the treatment, was determined. The therapeutic schedule was presented, with emphasis on the correlation between adverse reactions and the total dose of 18 grams, approximately, as well as taking into consideration precautions to assure the safety of the treatment. Quantitative serological reactions consisting of complement fixation, indirect immunofluorescence, indirect hemagglutination, and, occasionally, ELISA, were used. Cure was found in 76 per cent of the acute patients but only in 8 per cent of those with chronic forms of the disease. In the light of such contrasting results, fundamentals of the etiological therapy of Chagas disease were discussed, like the criterion of cure, the pathogenesis and the role of immunosuppression showing tissue parasitism in long standing chronic disease, in support of the concept that post-therapeutic consistently positive serological reactions mean the presence of the parasite in the patient's tissues. In relation to the life-cycle of T. cruzi in vertebrate host, there are still some obscure and controversial points, though there is no proof of the existence of resistant or latent forms. However, the finding over the last 15 years, that immunosuppression brings about the reappearance of acute disease in long stand chronic patients justifies a revision of the matter. Facts were quoted in favor of the treatment of chronic patients.

Acute Disease↗

Clinical ecology. American College of Physicians.

Clinical ecologists propose the existence of a unique illness in which multiple environmental chemicals, foods, drugs, and endogenous C. albicans have a toxic effect on the immune system, thereby adversely affecting other bodily functions. The proposal uses some concepts that superficially resemble those that apply to clinical allergy and toxicology and others that are novel. Review of the clinical ecology literature provides inadequate support for the beliefs and practices of clinical ecology. The existence of an environmental illness as presented in clinical ecology theory must be questioned because of the lack of a clinical definition. Diagnoses and treatments involve procedures of no proven efficacy. Case reports by clinical ecologists and evaluation of these patients by other physicians indicate that this diagnosis is applied most frequently to persons with symptoms of physiologic (somatic) or psychologic dysfunction, or both. Proof of cause-effect relations between environmental factors and symptoms of "environmental illness" is particularly difficult because clinical ecologists implicate such a broad range of agents, including chemicals, foods, hormones, and microorganisms. Most patients are believed to react to multiple environmental substances by any route of exposure, and some are said to be intolerant to the entire environment, the so-called "total allergy syndrome." The principal method of proof cited by clinical ecologists for the existence of "environmental illness" is the symptom-provocation test used in diagnosis of individual cases after the condition is suspected because of a history of symptoms and suspected causes. Published studies on the provocation test employed widely different subject-selection methods and outcome-measurement criteria. All were seriously flawed by the absence of matched patient-control groups, absence or inadequacy of the placebo, and failure to achieve or document randomness of trials. Not surprisingly, therefore, the conclusions from these studies are conflicting. Those studies reporting results of immunologic tests are insufficient to address theories of environmental illness; the number of cases is small and selection criteria are not clear. Enumeration of lymphocyte subsets and quantitation of serum immunoglobulin and complement levels in patients with "environmental illness" have not yielded clear-cut evidence of immunologic abnormality. Clinical ecologists use a treatment program that includes avoidance of environmental chemicals, rotation of foods in the diet, and neutralization of symptoms with injected or sublingual extracts. Except for small-dose oral nystatin, which is used for treatment of patients with the candida hypersensitivity syndrome, drug therapy is intentionally avoided, although some clinical ecologists recommend mineral salts, oxygen, vitamins, minerals, and antioxidants for relief of symptoms.(ABSTRACT TRUNCATED AT 400 WORDS)

Environmental Exposure↗

New monoclonal antibodies specific for the guinea pig line 10 hepatocarcinoma.

Monoclonal antibodies reactive to line 10 (L10) hepatocarcinoma cells, but not to L2C leukemia cells, of strain 2 guinea pig were produced and characterized. Complement-mediated cytolysis assay and quantitative absorption analysis revealed that one of the monoclonal antibodies, 3C4 antibody (IgG2a), was highly specific for L10. Neither normal guinea pig tissues including adult and fetal liver, nor other hepatomas of strain 2 guinea pig, line 1 (L1) and Hepatoma III, were reactive with the 3C4 antibody. Another antibody, 2E4 (IgM), was reactive to the liver, kidney and spleen cells but not to the thymocytes, lymph node cells, brain and red blood cells of the guinea pig. The 2E4 antibody reacted to Hepatoma III but not to L1 cells. Therefore, 3C4 antibody is specific to a tumor-associated antigen of L10 hepatoma, and 2E4 antibody is cross-reactive with a certain differentiation antigen of normal tissues. The 3C4 antibody showed antibody-dependent cytotoxicity. Since 3C4 antibody was different in the isotype and the antigen recognized from a monoclonal antibody (D3) which was reported from the NIH in the USA, 3C4 is a new monoclonal antibody reactive with L10 hepatocarcinoma.

Animals↗

[Comparison of different methods of medical images in the assessment of local extension of osteogenic sarcomas].

The authors compared different methods of medical visualisation (standard radiography, arteriography, quantitative isotope bone scan, telethermography, CT scan, visualisation by nuclear magnetic resonance) in 52 osteogenic sarcomas. In the majority of cases the diagnosis was suggested by standard X-rays at the first visit. CT scan and visualisation by nuclear magnetic resonance are the two basic examinations both in terms of assessing the future single block excision as well as deciding the approach to be used for biopsy. Telethermography and quantitative isotope bone scan usefully complement clinical examination and standard X-rays in following the course during chemotherapy. Arteriography is indicated only in the presence of large tumors threatening the vessels directly.

Adolescent↗

Recent advances in X-ray microanalysis in dermatology.

Electron microprobe and proton microprobe X-ray analysis can be used in several areas of dermatological research. With a proton probe, the distribution of trace elements in human hair can be determined. In contrast to sulfur, which is homogeneously distributed, calcium, iron, and zinc appear to be non-homogeneously distributed over the hair cross-section. Electron microprobe analysis on freeze-dried cryosections of guinea-pig and human epidermis shows a marked gradient of Na, P and K over the stratum granulosum. In sections of freeze-substituted human skin this gradient is less steep. This difference is likely to be due to a decrease in water content of the epidermis towards the stratum corneum. Electron microprobe analysis of the epidermis can, for analysis of trace elements, be complemented by the proton microprobe. Quantitative agreement between the two techniques can be obtained by the use of a standard. Proton microprobe analysis was used to determine the distribution of Ni or Cr in human epidermis exposed to nickel or chromate ions. Possible differences in water content between the stratum corneum of patients with atopic eczema and normal stratum corneum was investigated in skin freeze-substituted with Br-doped resin. No significant differences were observed. Proliferative reactions in the epidermis appear to be associated with increased levels of the elements P and K. Such changes were found in guinea-pig skin after exposure to sodium lauryl sulfate, and in plaques of skin from patients with psoriasis.

Animals↗

Enzyme labeled immunosorbant assay (ELISA) for detection of platelet antibodies.

Although it is widely accepted that patients with immune thrombocytopenia produce platelet antibodies, the demonstration of such antibodies has been difficult and time consuming. A simple and quick enzyme linked immunoassay for platelet antibodies is presented. The platelet associated IgG is coupled with alkaline phosphatase labeled anti-IgG. The resultant complex is determined spectrophotometrically using p-nitrophenyl phosphate as substrate. With this technique, excess of IgG on platelets was detected in 24 out of 33 patients (72 percent) with immune thrombocytopenic purpura and four out of four thrombocytopenic patients with systemic lupus erythematosus. The results of this assay correlate quantitatively with Dixon er al3 complement lysis inhibition assay (r = 0.82).

Autoantibodies↗

Serologically detectable MHC and tumor-associated antigens on B16 melanoma variants and humoral immunity in mice bearing these tumors.

We compared the expression of serologically detectable MHC and tumor-associated antigens on low and high metastasis variants of B16 melanoma tumor. Complement-dependent cytotoxicity, radioimmunobinding, and quantitative absorption assays showed that with respect to both types of antigens the low metastasis variant B16-F1 expressed a higher serologically detectable antigenicity than B16-F10, its high metastasis counterpart. A reverse situation existed in terms of in vivo immunogenicity of these metastasis variants. Sera from C57BL/6 mice bearing locally growing B16-F10 tumors had a higher binding activity to B16 cells than sera from B16-F1 bearers. Accordingly, in vivo propagating B16-F10 tumors had a higher content of tumor-associated Ig than B16-F1 tumors.

Animals↗

Breast imaging with fluorine-18-FDG PET: quantitative image analysis.

UNLABELLED: This study evaluated various quantitative criteria for analysis of breast imaging with PET using the radiolabeled glucose analog 18F-fluorodeoxyglucose (FDG). METHODS: In a prospective study, 73 patients with abnormal mammography or palpable breast masses scheduled for biopsy were investigated with PET. A total of 97 breast tumors were evaluated by histology, including 46 benign and 51 malignant tumors. Using a whole-body PET scanner, attenuation-corrected images were acquired between 40 and 60 min after tracer injection. For Patlak analysis, dynamic data acquisition was obtained in 24 patients. To differentiate between benign and malignant breast tumors, receiver operating characteristic curves were calculated using incrementally increasing threshold values for tumor/ nontumor ratios based on average and maximum activity values per region of interest, standardized uptake values (corrected for partial volume effect, normalized to blood glucose, partial volume effect and blood glucose, using the lean body mass as well as the body surface area) and calculating the FDG influx rate (K) assessed by Patlak analysis. RESULTS: Quantification of FDG uptake in breast tumors provided objective criteria for differentiation between benign and malignant tissue with similar diagnostic accuracy as compared with visual analysis. Applying correction for partial volume effect and normalization by blood glucose yielded the highest diagnostic accuracy. CONCLUSIONS: These quantitative methods provided accurate evaluation of PET data for differentiating benign from malignant breast tumors. Quantitative assessment is recommended to complement visual image interpretation with the potential benefit of reduced interobserver variability.

Breast Diseases↗

[Early post myocardial infarction syndrome--a trial of assessment based on clinical course and immunologic tests].

The study analysed clinical and immunological course of 22 patients (aged 56.3 +/- 9.5) with fever (38.5 degrees C) and greatly increased erythrocyte sedimentation rate (ESR) in the first week after myocardial infarction. The control group consisted of 25 patients (aged 50.7 +/- 11.2) without inflammatory and infectious diseases. Clinical courses of the disease, chest x-ray, echocardiography, leucocytosis and serial CK-MB levels were analysed. The immunological investigations involved quantitative estimation of IgG, C3 complement, C4 complement and the identification of T and B lymphocytes on the basis of the rosette tests A, E and EAC. Post myocardial infarction syndrome (PMIS) manifested by fever and greatly increased ESR we observed in 64% of examined patients, but fully manifested PMIS in 14% with tendency to recurrences. We found the differences in immunological examinations compared to the control group. Pericardial effusion occurred in 64% of the patients. The treatment with corticosteroids brought dramatic relief of the symptoms with objective improvement of clinical condition. Patients with high temperature with accompanying greatly raised ESR in the first week after MI may demonstrate abortive form of the post myocardial infarction syndrome.

Aged↗

Establishment of a concordant xenogeneic splenocyte injection model for the dynamic study of the marginal zone in the spleen.

BACKGROUND: This study was undertaken to establish a simple technique with which we could investigate the relationship between the marginal zone (MZ) in the spleen and antispecies antibody production, as well as to estimate the efficacy of various immunosuppressive treatments in xenotransplantation. METHODS: With a concordant xenogeneic combination (hamster-to-rat), the early phase reaction of the MZ was studied by use of quantitative histologic analysis, and complement-dependent cytotoxic antibody titers were determined in both a heart transplantation model and the splenocyte injection model. Furthermore, changes in the MZ were examined with isogeneic and allogeneic combinations with the splenocyte injection model. Next, the effect of cyclophosphamide, a promising immunosuppressant for concordant xenotransplantation, was examined by use of the splenocyte injection model. RESULTS: With a concordant xenogeneic combination, the MZ enlarged, and antihamster immunoglobulin M antibody synthesis increased after immunization in both models. On the other hand, with an isogeneic combination, the MZ did not expand, and with an allogeneic combination the MZ enlargement was not as great as that with a concordant xenogeneic combination. Cyclophosphamide suppressed the MZ expansion in a dose-dependent manner and effectively diminished antibody production in the splenocyte injection model. CONCLUSION: Dynamic studies of the MZ in the spleen with the splenocyte injection model are useful for the elucidation of the mechanisms of reaction and for estimating the efficacy of various immunosuppressive treatments in concordant xenotransplantation.

Animals↗

Thrombin and human plasma kallikrein inhibition during simulated extracorporeal circulation block platelet and neutrophil activation.

Cardiopulmonary bypass causes hemorrhagic complications, and initiates a chemical and cellular inflammatory response. Contact of blood with synthetic surfaces leads to qualitative and quantitative alterations in platelets, neutrophils, complement, and contact systems. Despite the fact that cardiopulmonary bypass is carried out in the presence of high doses of heparin, there is significant activation of both platelets and neutrophils. Thrombin is protected on cell and fibrin surfaces from antithrombin, even in the presence of high doses of heparin (approximately 5 U/ml). We therefore studied the effect of a small (Mr = 497), highly effective (Ki = 41 pM), reversible tripeptide inhibitor of thrombin, DUP 714 (1 microM), in a well characterized model of simulated extracorporeal circulation. In the absence of DUP 714, platelet counts decreased by 75% 5 min after the start of extracorporeal bypass and increased to 48% at 120 min of recirculation. DUP 714 significantly preserved platelet counts, decreased plasma levels of platelet beta-thromboglobulin levels, but did not prevent a decrease in sensitivity of platelets to adenosine diphosphate. Kallikrein-C1-inhibitor and C1-C1-inhibitor complexes increased progressively from 0.32 U/ml to 0.67 U/ml and from 4.45 U/ml to 7.25 U/ml, respectively, during 120 min of recirculation without DUP 714. Addition of DUP 714 significantly inhibited kallikrein-C1-inhibitor complex formation but did not affect C1-C1-inhibitor complexes. In the absence of DUP 714, human neutrophil elastase levels rose from a baseline of 0.01 +/- 0.00 microg/ml to 1.18 +/- 0.21 microg/ml during 120 min of recirculation. Human neutrophil elastase release at 120 min was significantly inhibited in the presence of DUP 714 to 37% of the value with heparin alone. These results indicated that addition of this novel thrombin (and kallikrein) inhibitor to heparin preserved platelet counts, decreased platelet secretion, and provided the additional benefit of partially blocking neutrophil activation during simulated extracorporeal circulation.

Cardiopulmonary Bypass↗

Aberrant regulation of complement by the erythrocytes of hereditary erythroblastic multinuclearity with a positive acidified serum lysis test (HEMPAS).

Susceptibility to hemolysis in acidified serum is a pathognomonic feature of hereditary erythroblastic multinuclearity with a positive acidified serum lysis test (HEMPAS, congenital dyserythropoietic anemia type II). The purpose of the studies reported herein was to determine if aberrant regulation of complement contributes to the susceptibility of HEMPAS erythrocytes to acidified serum lysis. The results of these experiments have demonstrated that regulation of both the C3 convertase of the alternative pathway and the membrane attack complex of complement by HEMPAS erythrocytes is aberrant. However, these abnormalities are not a consequence of quantitative or functional deficiencies of the erythrocyte complement-regulatory proteins, decay accelerating factor (DAF, CD55), or membrane inhibitor of reactive lysis (MIRL, CD59). Our recent studies have shown that glycophorin A (GPA), the major erythrocyte sialoglycoprotein is a complement regulatory protein. Analysis by radioimmunoprecipitation suggested that GPA on HEMPAS erythrocytes is abnormally glycosylated. Further analysis indicated that the abnormality involves the O-linked oligosaccharide moiety. Together, these studies show that complement regulation by HEMPAS erythrocytes is abnormal and that constituents other than DAF and MIRL participate in controlling complement activation on the erythrocyte membrane. Additionally, these studies suggest that the glycosylation defect that is characteristic of HEMPAS involves GPA.

Anemia, Dyserythropoietic, Congenital↗

Comparison of three serological methods for the detection of hepatitis-associated antigen.

Serum hepatitis (Australia) antigen in the sera of hepatitis patients and carriers can be detected in one and a half to three hours by crossover electrophoresis. The method is more sensitive than the immunodiffusion technique commonly employed in this field. It is of the same order of sensitivity as complement fixation but is less complicated.Crossover electrophoresis is thus the method of choice for the rapid screening of sera for hepatitis antigen; complement fixation may be used for quantitative determination of antigen in positive cases.

Acute Disease↗

Sex, MHC and complement C4 in autoimmune diseases.

Autoimmune diseases are estimated to affect 10-50 million people in the United States, and untold millions worldwide. Nearly 80% of all people with autoimmune diseases are women, and a strong association of these diseases with MHC genes has been known for some time. However, very little is known about what causes autoimmune diseases or the factors that lead to disease recurrence. The sex-associated differences in multiple sclerosis (MS) and the mouse model of MS, experimental autoimmune encephalomyelitis (EAE), are associated with MHC genetic background, sex hormone levels and cytokine production. The implication of these factors has aided the identification of new autosomal genetic susceptibility loci. Complete deficiencies of early complement components are strongly associated with systemic lupus erythematosus (SLE) but the role of complement proteins in SLE is not yet clear. Recent data suggest that quantitative and qualitative diversities of the MHC-linked complement C4 among different ethnic groups can be important in the susceptibility and disease severity of SLE.

Animals↗

[Changes in complement breakdown products and terminal complement complex in patients with acute glomerulonephritis].

In this study we examined the role of the complement system in acute glomerulonephritis (AGN). Breakdown products of complements (iC3b, C4d and Bb) and Terminal complement complex (TCC, SC5b-9 complex) in plasma samples were measured by ELISA. The microassay plates were coated with monoclonal antibodies which bind specifically to human iC3b, C4d, Bb and SC5b-9 complex. This assay accurately quantitates small amounts of in vivo complement activation. The plasma samples were drawn from patients with AGN and other glomerulonephritis. There were some patients with various glomerulonephritis whose plasma iC3b, C4d and Bb concentrations were higher than those in normal human. However specificity was not found. The ratios iC3b/C3 and C4d/C4 were increased in the early stages of AGN, but plasma Bb concentrations revealed no significant changes. Plasma SC5b-9 complex concentrations were increased in the early stages of AGN. C3c, C3d, C4d and SC5b-9 were found to be localised in the glomeruli of those AGN patients. It is suggestive that in these cases of AGN (especially case 2) complement activation is predominantly mediated through the classical pathway and TCC is formed by this activation. This complement activation in the blood and the renal tissue is presumed to be involved in the initiation and progression of AGN.

Acute Disease↗

Quantitative evaluation of urinalysis test strips.

BACKGROUND: Urine test strip results are generally reported in categories (i.e., ordinal scaled), but automated strip readers are now available that can report quantitative data. We investigated the possible use of these meters to complement flow cytometry of urine and compared reflectance readings with quantitative determinations of urinary glucose and microalbumin. METHODS: We compared URISYS 2400 (Roche) quantitative reflectance data with data from the UF-100 (Sysmex) and biochemical data for 436 nonpathologic and pathologic urine samples. RESULTS: Reproducibility of the reflectance signal was good for high- and low-concentration urine pools for protein (0.8% and 0.9% and 1.5% and 2.2% within and between runs, respectively), leukocyte esterase (1.1% and 1.0%; 5.1% and 1.2%), hemoglobin (1.7% and 1.1%; 8.9% and 1.1%) and glucose (2.1% and 0.5%; 6.5% and 2.3%). Fair agreement was obtained between UF-100 and test strip reflectance data for erythrocytes and hemoglobin (r = -0.680) and leukocytes and leukocyte esterase (r = -0.688). Higher correlations were observed for biochemical and test strip data comparing protein and albumin (r = -0.825) and glucose data (r = -0.851). The lower limits of detection for erythrocytes and leukocytes were 8 x 10(6)/L and 19 x 10(6)/L, respectively. The protein test (n = 220) detected 86% (95% confidence interval, 78-92%) of samples with <30 mg/L albumin with a specificity of 84% (95% confidence interval, 76-91%). CONCLUSIONS: In urine test strip analysis, quantitative hemoglobin and leukocyte esterase reflectance data are complementary with flow cytometric results and glucose and albumin results.

Albumins↗