Cost-benefit analysis of spinal cord stimulation for intractable angina pectoris: a win-win scenario?
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Angina Pectoris↗
Biomedical subjects
J Regan
Publications and source records attributed to J Regan.
Anionic- and lipophilic-mediated surface binding inhibitors of human leukocyte elastase.
We report the synthesis of a series of diphenylmethane-based oligomers containing anionic and lipophilic functionalities that are potent inhibitors of human leukocyte elastase (HLE). The enzyme inhibition is regulated by the size of the oligomer, as well as, the number of charges. Lipophilicity is an important element in determining potency and specificity against other basic enzymes. Compounds whose scaffolds contain three phenoxyacetic acid groups and three alkyl ethers are competitive and specific inhibitors of HLE with Ki = 20 nM. The mechanism of action of this class of compounds is believed to involve multidendate interactions with the surface of HLE near the active site which prevents substrate access to the catalytic site.
Benzhydryl Compounds↗
Characterization of anti-thymoglobulin, anti-Atgam and anti-OKT3 IgG antibodies in human serum with an 11-min ELISA.
Patients treated with OKT3 may become resistant to OKT3 therapy following induction of anti-idiotypic antibodies. Antirabbit or antihorse antibodies following Thymoglobulin (rabbit antithymocyte globulin (ATG) or Atgam (horse ATG) therapy may not similarly inhibit drug efficacy due to an insufficient anti-idiotypic response against the multiple idiotypic specificities of the polyclonal anti-T cell preparations. However, no standardized assay had been developed to monitor antihorse and antirabbit antibodies. To address this issue, we developed three rapid (11-min) and standardized semiquantitative plate enzyme-linked immunoassays (ELISAs) to monitor human serum immunoglobulin-G (IgG) antibodies to Orthoclone OKT3 IgG2a, Atgam and Thymoglobulin. The format was identical for the three assays, with the exception of the immunoglobulin antigen coated on the ELISA plates. As OKT3 is a monoclonal antibody, OKT3 itself is used as the capture antigen. However, for antibody responses against the polyclonal antibody preparations Atgam and Thymoglobulin, it was found that horse IgG and rabbit IgG respectively were equivalent to Atgam and Thymoglobulin as capture antigens. Excellent correlation with a 3.5-h format was demonstrated (r values between 0.986 and 0.845). Specificity was demonstrated by inhibition experiments. Correlations between endpoint titres calculated from serial dilutions and 1:50 dilution OD values were 0.821, 0.983 and 0.937 respectively for the mouse, horse and rabbit assay. High titre sera were selected to assess their ability to block in vitro the binding of OKT3, Thymoglobulin and Atgam to T cells, using flow cytometry. None of the sera containing antihorse (n = 9) or antirabbit (n = 8) antibodies blocked T cell binding of Atgam or Thymoglobulin. In contrast, OKT3 binding was blocked by the four highest titre sera of the 13 anti-OKT3 sera tested. Consequently, prospective monitoring of treated patients using standardized 11-min assays may allow a better assessment of the effect of presensitization to OKT3, Atgam or Thymoglobulin.
Animals↗
Vaginal colonization or infection with Candida albicans in human immunodeficiency virus-infected women during pregnancy and during the postpartum period. Women and Infants Transmission Study Group.
We evaluated the relationship between immunologic status and vaginal colonization or infection with Candida albicans for 605 women enrolled in a multicenter, prospective cohort study of mother-to-infant transmission of human immunodeficiency virus type 1 (HIV-1). A low CD4+ lymphocyte level (< 14% vs. > or = 14%, which corresponds to an absolute count of approximately 200 x 10(6)/L) was associated with a two- to fivefold increased likelihood of vaginal colonization (odds ratio [OR], 2.28; 95% confidence interval [CI], 1.01-5.19) and vaginal candidiasis (OR, 3.08; 95% CI, 1.21-7.71) during pregnancy and during the postpartum period (OR, 2.98; 95% CI, 1.51-5.88 and OR, 5.45; 95% CI, 1.73-16.6, respectively). These associations persisted in multivariate logistic regression analyses. No associations with CD8+ lymphocyte levels or CD8+ CD38+ or other lymphocyte subset levels were found after adjustment for CD4+ cell level and other covariates. However, postpartum (but not antepartum) antibiotic use and pregnancy were also associated with vaginal colonization and candidiasis (P < or = .001 for each). Vaginal candidiasis was not associated with an increased risk of mother-to-infant transmission of HIV-1; however, a related, more inclusive variable, clinical vaginitis or vaginosis of any etiology at the last antepartum visit, was associated with mother-to-infant transmission (OR, 1.92; 95% CI, 1.07-3.43). These findings emphasize the complex, multifactorial nature of vaginal candidiasis and highlight the need for safe and effective treatment and prevention strategies for women with advanced HIV infection.
Adult↗
Effect of intensive treatment of diabetes of the risk of death or renal failure in NIDDM and IDDM.
OBJECTIVE: To examine the effectiveness and safety of long-term intensive therapy in NIDDM and IDDM. RESEARCH DESIGN AND METHODS: In a private practice setting with a multi-disciplinary team, we compared the rates of total mortality, cardiac-specific mortality, and severe renal failure over 14 years in a cohort of 780 eligible patients, 209 patients with a longer duration of intensive therapy (median duration > 11 years, group I) and 571 patients with shorter duration of intensive therapy (median duration < 1 year, group II). A comorbidity index was used to assess the degree of prognostic risk at baseline. A comprehensive diabetes program was the therapeutic intervention. The endocrinologists and diabetes care team provided primary care, aggressive cardiovascular screening, and risk reduction. Intensive insulin therapy was used in 95.7% of group I IDDM and 66.0% of group I NIDDM patients. RESULTS: The overall median HbA1c for group I was 7.3%. Compared with group II, the overall reduction in cumulative total mortality in group I was 22%. In the cohort with less severe initial comorbidity, the reduction in total mortality was 45%. We found similar reductions in renal failure rates in IDDM and in cardiac mortality in NIDDM patients on intensive insulin therapy. CONCLUSIONS: This comprehensive diabetes program is associated with lowered mortality and morbidity in both IDDM and NIDDM. Intensive insulin therapy in long-term patients with NIDDM does not increase cardiac mortality. Intensive therapy is safe and effective in NIDDM within the context of a comprehensive program.
Adult↗
Assessment and evaluation: keys to the success of adult day services.
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Activities of Daily Living↗
Correlation of ELISA-detected IgG and IgA anti-HLA antibodies in pretransplant sera with renal allograft rejection.
The present study compared the occurrence of rejection episodes during the first twelve posttransplant (Tx) months and the 1-, 2-, and 3-year graft survivals among recipients stratified by the percent panel reactive antibody (% PRA) of pre-Tx sera as detected using either an antihuman globulin determined PRA (AHG-% PRA) or an ELISA methodology detecting IgG reactive against soluble HLA class I antigens (% PRA-STAT). There was a significant correlation between AHG-PRA greater than or equal to 10% and a PRA-STAT greater than or equal to 10% (P<0.001). However, among 200 sera displaying an AHG-PRA greater than or equal to 10% (mean 57 +/- 2l%), only 69% (138/200) displayed a PRA-STAT greater than or equal to 10%. With further study the discrepant finding, of 62 sera that were AHG-PRA greater than or equal to 10% but PRA-STAT <10%, was due to the presence of IgM and/or IgG non-MHC reactivity. In contrast, among 293 sera displaying an AHG-PRA < 100% (mean 3 +/- 2%), 15% (43/293) displayed a PRA-STAT greater than or equal to 10%. There was no correlation between AHG-% PRA and rejection episodes occurring during the first twelve post Tx months. In contrast, however, there was a highly significant correlation between PRA-STAT greater than or equal to 10% and the occurrence of rejection episodes during the first twelve post-Tx months (P < 0.001). Patients with PRA-STAT greater than of equal to 10% experienced a 70% rejection frequency compared with the 35% rejection frequency for patients with PRA-STAT sera < 10% (P<0.001). A significant correlation was observed between the presence of IgG-1 and rejection (P<0.01) but not IgG-subclasses 2, 3, or 4. Of particular interest was the observation in 11 patients that the presence of ELISA-detected IgA anti-HLA class I antigen (ELISA-IgA PRA greater than or equal to 10%) was associated with a significantly reduced rejection risk compared with sera where only PRA-STAT greater than or equal to 10% was present (27% vs. 70% incidence of rejection episodes, P<0.01). Finally, patients displaying pretransplant PRA-STAT results < 10% experienced significantly improved l-, 2-, and 3- year graft survivals of 85% vs. 74%, 82% vs. 70% and 81% vs. 67%, respectively (P<0.01 for each time point), compared with patients displaying PRA-STAT results greater than or equal to 10%. These data suggest that the use of the ELISA methodology to detect IgG reactivity against soluble HLA class I antigens (PRA-STAT) may allow for the determination of a more clinically informative % PRA than the AHG-% PRA. Moreover, the presence of ELISA-detected IgA anti-HLA may act to inhibit rejection mechanisms associated with ELISA-detected IgG anti-HLA greater than or equal to 10%.
Enzyme-Linked Immunosorbent Assay↗
Pretransplant rejection risk assessment through enzyme-linked immunosorbent assay analysis of anti-HLA class I antibodies.
Soluble HLA enzyme-linked immunosorbent assays (ELISAs) for the detection of anti-HLA class I immunoglobulin G (IgG), IgG1, IgG2, IgG3, IgG4, IgM, and IgA antibodies were developed and used to analyze retrospectively the correlation between pretransplant allosensitization and posttransplant rejection episodes in renal allograft recipients. Enzyme-linked immunosorbent assay plates were coated with 46 different soluble HLA preparations representing 40 different HLA class I antigens. After incubation with a serum specimen, bound antibodies were detected with a peroxidase-conjugated antibody. Serum specimens from 85 patients were analyzed. All patients tested positive by microlymphocytotoxicity (ie, >5% panel-reactive antibody [PRA]). Approximately half (56%) of the patients had experienced one or more rejection episodes within 12 months posttransplantation. Fifty-five patients tested positive by ELISA (total IgG %PRA >10%). A strong correlation between first-year rejection and ELISA-detected anti-HLA class I IgG1 was observed (P = 0.0004). The predictive value for IgG1 and first-year rejection was 77.5%, demonstrating that ELISA results identify patients at high risk of rejecting the transplanted kidney. Anti-HLA class I total IgG detected by ELISA also correlated with first-year rejection episodes (P = 0.04). The presence of anti-HLA class I IgG2, IgG3, IgG4, or IgM was not predictive of first-year rejection episodes. Anticlass I IgA antibodies were only found in combination with anti-class I IgG1 antibodies.
Antibody Specificity↗
Thoracoscopic Surgery of the Spine.
Anterior approach to the thoracic spine has been limited by the morbidity of a thoracotomy. By a thoracoscopic approach, a majority of thoracic spine procedures can now be performed from the anterior approach including diskectomy for herniation, release for correction of spinal deformity and corpectomy for tumor. Although experience is limited and results still short term, the thoracoscopic approach appears to be a promising one for the treatment of thoracic spine disease.
Journal Article↗
Filling Tec 5 vaporizers.
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Anesthesiology↗
Detection of panel-reactive anti-HLA class I antibodies by enzyme-linked immunosorbent assay or lymphocytotoxicity. Results of a blinded, controlled multicenter study.
A soluble HLA ELISA for the detection of anti-HLA class I IgG antibodies was developed and compared to complement-dependent microlymphocytotoxicity. ELISA plates were coated with a panel of sHLA class I antigens isolated from the culture supernatants of 46 different EBV-transformed phenotyped B-cell lines. After the incubation of the coated plates with test serum, bound antibodies were detected using a peroxidase-conjugated anti-human IgG antibody. Absorbance was read using an ELISA plate reader and assay results were analyzed by computer. Antibody specificities were determined by Fisher's exact test tail analysis. The reproducibility of ELISA assay results was evaluated in a blinded, controlled multicenter study. A total of 102 serum specimens from patients on waiting lists to receive kidney transplants were tested five times by ELISA in five different laboratories. The correlation coefficients (r) of %PRA values determined by ELISA ranged from 0.89 to 0.96, and the average agreement on qualitative assay results (antibody positive vs antibody negative) was 98%. Endpoint titration of several serum specimens demonstrated equivalent sensitivity of ELISA and microlymphocytotoxicity (using the anti-globulin antibody protocol). Most of the antibody specificities determined by ELISA were in agreement with specificities determined by microlymphocytotoxicity. To evaluate the correlation of ELISA and microlymphocytotoxicity (CDC) assay results the same 102 specimens were tested six times by CDC in five different laboratories. The interlaboratory correlation coefficient (r) of %PRA values determined by microlymphocytotoxicity ranged from 0.57 to 0.94, and the average agreement on qualitative assay results was 85%. A comparison of ELISA with microlymphocytotoxicity was performed using consensus microlymphocytotoxicity results. This showed a high correlation (r = 0.81) of %PRA values determined by ELISA and microlymphocytotoxicity. This demonstrates that the detection of anti-HLA class I antibodies by soluble HLA ELISA is a reliable alternative to microlymphocytotoxicity testing.
Antibody Specificity↗
The influence of breast size on late radiation effects and association with radiotherapy dose inhomogeneity.
A prospective assessment of late changes in breast appearance in 559 patients after tumour excision and radiotherapy for early breast cancer noted a strong association with breast size. Only 3/48 (6%) patients with small breasts developed moderate or severe late changes compared with 94/423 (22%) with medium sized breasts and 34/88 (39%) patients with large breasts (p < 0.001). One possibility is that greater radiation changes are related to greater dose inhomogeneity in women with large breasts. To explore this hypothesis, radiation dose distributions were assessed in a separate group of 37 women in whom three-level transverse computer tomographic images of the breast in the treatment position were available. A significant correlation was found between breast size and dose inhomogeneity which may account for the marked changes in breast appearance reported in women with large breasts.
Adult↗
Antiproliferative activity to vascular smooth muscle cells and receptor binding of heparin-mimicking polyaromatic anionic compounds.
Proliferation of bovine aortic smooth muscle cells (SMCs) induced by thrombin, basic fibroblast growth factor, or serum is inhibited by anionic, nonsulfated aromatic compounds that mimic many of the effects of heparin. Among these compounds are aurintricarboxylic acid (ATA) and a newly synthesized polymer of 4-hydroxyphenoxy acetic acid (compound RG-13577). Iodinated- or 14C-labeled compound RG-13577 binds to cultured SMCs in a highly specific and saturable manner. Scatchard analysis of the binding data revealed the presence of an estimated 1 x 10(7) binding sites per cell with an apparent dissociation constant of 3 x 10(-6) mol/L. Binding of radiolabeled RG-13577 was efficiently competed for by related aromatic anionic compounds and by apolipoprotein E, but not by heparin, heparan sulfate, suramin, or various purified growth factors and extracellular matrix proteins. Receptor cross-linking of SMC-bound 125I-RG-13577 revealed a single species of high M(r) (approximately 280 kD) cell surface receptors detected in the absence but not the presence of excess unlabeled compound RG-13577. Binding was susceptible to downregulation and restoration of receptor levels in a manner similar to that of hormone and growth factor receptors. We suggest that the antiproliferative activity of compound RG-13577 and related compounds is initiated by binding to specific growth-inhibiting cell surface receptors. Heparin-mimicking compounds may be applied to inhibit SMC proliferation associated with atherosclerosis and restenosis.
Animals↗
Provision of a community perinatal service in a developing country.
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Developing Countries↗
Rabbit and human renotropin are not epidermal growth factor.
Sera obtained from rabbits and humans after unilateral nephrectomy (uni sera) compared with sera obtained preoperatively (control sera) significantly stimulate 3H-thymidine incorporation into the DNA of cultured renal tissue from the respective species. In contrast, rabbit liver cells in culture are not stimulated by the uni sera compared with control sera obtained from rabbits. Mouse epidermal growth factor (EGF) added to tissue cultures significantly stimulates both kidney and liver cells of rabbits and kidney cells of humans. Antiserum against EGF overcomes, at least to some extent, the enhancing effect of EGF under all circumstances, but does not influence the stimulatory ability of uni serum obtained from rabbit and human kidney cells from the respective species. In addition, the activity of EGF was not different in the presence of uni and control sera. This study corroborates the presence of renotropic activity in the sera of rabbits and humans after removal of functioning renal mass and shows that this activity is not derived from EGF, nor does it work by potentiating some aspect of the EGF system.
Animals↗
Production of prostatic lesions in canines using transrectally administered high-intensity focused ultrasound.
High-intensity focused ultrasound is a method of destroying tissue at a point distant from the transducer without injuring intervening tissue. A transrectal probe was developed and used to treat 26 canines in order to determine the feasibility of using this therapy in humans. Lesions of coagulative necrosis which evolved into cystic cavities were produced. Surrounding tissue was preserved without evidence of injury.
Animals↗
Reversal of basic fibroblast growth factor-mediated autocrine cell transformation by aromatic anionic compounds.
NIH-3T3 cells transfected with basic fibroblast growth factor (bFGF) fused to a signal peptide sequence (spbFGF cells) are transformed in vitro and tumorigenic in vivo. Treatment of spbFGF cells with low and nontoxic concentrations (0.5-2.5 micrograms/ml) of negatively charged, nonsulfated aromatic compounds (e.g., aurin tricarboxylic acid, 4-hydroxyphenoxyacetic acid) resulted in restoration of their normal proliferative rate, morphological appearance, and adhesion properties. Binding and cross-linking experiments using 125I-labeled bFGF revealed that these alterations were associated with an up-regulation of high affinity receptors bFGF receptors was induced by these compounds in spbFGF cells that were seeded on fibronectin to enforce a firm cell attachment and flattening. Thus, induction of spbFGF cell adhesion and spreading may not be related to restoration of normal bFGF-receptor interactions. Although the negatively charged aromatic compounds mimic many of the effects of heparin in other systems (e.g., release of heparin- and heparan sulfate-bound proteins, inhibition of heparanase), heparin, heparan sulfate, and dextran sulfate were not effective at the low concentrations of the anionic compounds used in the present study. Likewise, suramin, a sulfated aromatic molecule, was effective at toxic concentrations, 400-600-fold higher than the nonsulfated aromatic compounds. The development of defined, nontoxic anionic compounds may provide a new strategy to interfere with the autonomous and anchorage independent mode of cell growth involved in autocrine cell transformation and cancer.
3T3 Cells↗
Cosmetic and functional outcomes of breast conserving treatment for early stage breast cancer. 1. Comparison of patients' ratings, observers' ratings, and objective assessments.
The cosmetic and functional results of breast conserving therapy were evaluated in a sample of 76 patients with early stage breast cancer, treated by wide local excision, axillary dissection and postoperative radiotherapy between 1975 and 1985. A comparison was made between patients' ratings, independent ratings by two observers (an oncology nurse and a radiation oncologist) and objective measurements. In approximately 40% of the cases, moderate to large differences in the appearance of the treated versus the untreated breast were reported by patients and clinical observers alike. When evaluated on an individual level, the observers' ratings showed relatively high inter-rater agreement (kappa = 0.64), but low levels of concordance were found between the patients' and observers' ratings (kappa < 0.10). Approximately half of the patients reported limited arm or shoulder function, generally mild in nature. Compared to the patients', the observers' ratings of arm edema were significantly lower, indicating 20% mild and 5% more severe swelling. Objective measures of cosmesis and function correlated moderately with the observers' and patients' ratings. Both cosmetic and functional results were found to be significantly related to time elapsed since treatment, with patients treated longer ago exhibiting more problems. The cosmetic and functional outcomes were not related to the patients' age. The results suggest that the patients' opinion can provide important additional information in the evaluation of cosmetic and functional results of breast conserving treatment.
Adult↗