Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 1770368 | Preoperative nutritional status of total joint patients. Relationship to postoperative wou | 1991 Dec | The records of 217 consecutive patients who underwent a primary total hip or total knee arthroplasty were reviewed for preoperative and postoperative nutritional status. Fifty-seven patients had a lymphocyte count of less than 1,500 cells/mm3, four patients had an albumin level of less than 3.5 g/dL, and two patients had both, giving a 27% incidence of indices indicative of preoperative nutritional depletion. Patients without wound complications had an average preoperative lymphocyte count of 1,995 (+/- 631), compared to 1,638 (+/- 491) for those with persistent serous drainage from their wounds, and 1,553 (+/- 419) for those patients with a major wound complication (P = .002). The average albumin levels were 4.30 (+/- 0.33), 4.22 (+/- 0.31), and 4.13 (+/- 0.54), respectively. Patients with rheumatoid arthritis were compared to those with osteoarthritis and were found to have significantly lower preoperative albumin levels. They were three times as likely to develop a major wound complication. Patients on immunosuppressive medications had significantly lower preoperative lymphocyte counts, lower albumin levels, and higher complication rates (P = .04). After operation, lymphocyte counts of all patients dropped to an average of 57% of their preoperative values, and albumin levels dropped to 72% of their preoperative values. No nutritional parameters had returned to their preoperative levels by 10 postoperative days. For all patients, a preoperative lymphocyte count of less than 1,500 cells/mm was associated with a five times greater frequency of developing a major wound complication, and an albumin level of less than 3.5 g/dL had a seven times greater frequency.(ABSTRACT TRUNCATED AT 250 WORDS) | |
| 1934804 | Absent or faint renal uptake on bone scan. Etiology and significance in metastatic bone di | 1991 Aug | A review of 14,296 unselected bone scans identified 889 scans showing absent or faint renal uptake. The majority of cases were associated with renal insufficiency (816/889; 91.8%), while widespread metastatic bone disease was the most common cause in a group of patients without renal disease (53/889; 6.0%). Of the 140 patients with prostate cancer, 108 (77.1%) had evidence of bone metastasis, 19 of whom (17.6%) revealed absent or faint renal uptake, demonstrating that poor renal uptake is more frequently associated with prostate cancer than with any other malignancy. Of note was that 162 out of 328 (49.4%) patients with stomach cancer at varying stages showed evidence of bone metastasis, and 14 of them (8.6%) showed poor renal images on bone scan. Interestingly, ankylosing spondylitis and rheumatoid arthritis were occasional causes of lack of renal activity (4 and 3 cases, respectively). A case of adult-form osteopetrosis, showing strikingly increased uptake mainly in the long bones with markedly diminished renal uptake, was also included in this study. Of the 53 bone scans with metastatic disease showing poor renal uptake, 44 (83.0%) revealed evidence of diffuse or multiple metastases in both spine and ribs, while 49 (92.5%) showed malignant involvement in three or more regions and 35 (66.0%) in four or more regions, suggesting widespread bone involvement in most cases. | |
| 1936027 | Pathomorphological aspects, aetiology and natural history of acquired mitral valve stenosi | 1991 Jul | Commissural fusion, leaflet thickening and alteration of the subvalvular apparatus are dominant mechanisms causing clinically important mitral stenosis (MS) of rheumatic origin. Calcification and a consequent decrease in leaflet mobility are subsequent features in rheumatic MS and may be the primary mechanisms in MS of degenerative origin. In 1051 consecutive patients with pure or predominant MS requiring surgical intervention, aetiology was rheumatic in 76.9%, infective in 3.3%, degenerative (severe annular and leaflet calcification) in 2.7% and congenital (Lutembacher syndrome) in 1.2%; it was the result of systemic lupus erythematosus (n = 4), carcinoid heart disease (n = 2), endomyocardial fibrosis (n = 2) and rheumatoid arthritis (n = 2) in less than 1%, while in 14.5% of these patients aetiology remained unclassified. The natural history of rheumatic MS is characterized by an asymptomatic latent period, following the initial rheumatic fever (RF). In a prospective study of MS (n = 159) the mean interval between RF and the appearance of symptoms was 16.3 +/- 5.2 years. Twenty-five years after the initial RF 8% of the patients were still asymptomatic, 9% were class II (NYHA), 33% class III and 50% had been operated or were class IV. Progress from mild to severe disability took 9.2 +/- 4.3 years on average. When valve surgery was indicated but refused by the patients, survival with medical treatment was 0.44 +/- 0.06 after 5 years, 0.32 +/- 0.08 after 10 years and 0.19 +/- 0.09 after 15 years.(ABSTRACT TRUNCATED AT 250 WORDS) | |
| 1709332 | Human osteoblastlike cells do not respond to interleukin-6. | 1991 Feb | Interleukin 6 (IL-6) exerts well-established effects on cells of the immune system as well as on various other cell types. It has been implicated in the control of connective tissue cells in such conditions as rheumatoid arthritis and osteoporosis. We have investigated the effects of recombinant human interleukin-6 (rhIL-6) on human osteoblastlike cells derived from explants of trabecular bone. ROS 17/2.8 cells were used as an additional osteoblastlike cell model system. We were unable to identify any effects of rhIL-6 (5-5000 pg/ml) on the proliferation, alkaline phosphatase activity. osteocalcin production, or release of cytokines or prostaglandins by either osteoblastlike cell model system. Since we have shown previously that these cells release IL-6 in culture, we used a sheep anti-human IL-6 antibody to investigate the possibility that (1) action of added exogenous IL-6 could be masking endogenous production, and (2) endogenous IL-6 may regulate the effects of osteotropic agents on the osteoblastlike cells. Presence of the antibody exerted no detectable effects on 1,25-(OH)2D3-stimulated alkaline phosphatase or on proliferation or TNF production enhanced by IL-1. Thus IL-6 does not appear to be involved in the regulation of osteoblast activity. | |
| 2020658 | Clinical implications of nodal reactive follicular hyperplasia in the elderly patient with | 1991 Jan | In older persons, the humoral immune response, as reflected morphologically by proliferation and expansion of germinal centers, is relatively subdued in comparison with the florid reactive follicular hyperplasia (RFH) which may be observed in younger age groups. The presence of RFH in lymph node biopsies in patients 60 yr or older, which we have regarded with concern since 1972, appears to represent an imbalance of the immune system, in some patients, on the background of which predominantly non-Hodgkin's malignant lymphoma (NHL) may be present or will develop. Fifty-eight patients 60 yr old or more who presented with enlarged lymph nodes exhibiting inappropriate RFH for age were identified during the interval from 1969 to 1989. An apparent etiology was initially identified for the reactive follicular hyperplasia in only 12 cases: five with documented rheumatoid arthritis; one each with a history of trauma, positive monospot test, and combination of thrombophlebitis and fungal skin infection, and two each with elevated Epstein-Barr virus (EBV) titers and human immunodeficiency virus type 1 (HIV-1) seropositivity. While most were alive or died of nonlymphomatous causes and one was lost to follow-up, 18 (31%) patients either had concurrent lymphoma or subsequently developed diffuse NHL. There were ten diffuse interfollicular (I-Foll) lymphomas (six concurrent), two diffuse mixed cell lymphomas (DMCL), one diffuse large cell lymphoma (DLCL), one diffuse immunoblastic sarcoma (DIBS), two diffuse small noncleaved cell lymphomas (DSNCL), one unclassified NHL, and only one Hodgkin's disease.(ABSTRACT TRUNCATED AT 250 WORDS) | |
| 2292594 | Myeloid calcium binding proteins: expression in the differentiated HL-60 cells and detecti | 1990 Oct | A differentiation antigen induced in 1,25-dihydroxyvitamin D3 (VD3)-treated HL-60 cells was identified as being comprised of the myeloid calcium binding proteins CaBP-p8 and -p14 by determining its amino acid and DNA sequence. Northern blot analysis using a DNA fragment of the gene encoding p14 as a probe indicated that the gene was not expressed in undifferentiated HL-60 cells but transcribed starting on day 1 after VD3 treatment. The level of p 14 mRNA reached a peak on day 2, then declined, and little mRNA remained on day 10, indicating that the p14 gene is activated once and then inactivated during HL-60 differentiation due to VD3. In contrast, thymidylate synthase (TSase) mRNA was present in undifferentiated HL-60 cells but disappeared quickly after VD3 treatment. Both p8 and p14 of CaBP were found at elevated levels in sera of some patients with connective tissue diseases [highly elevated in rheumatoid arthritis (RA), Sjogren's syndrome (SjS), systemic lupus erythematosus (SLE), and progressive systemic sclerosis (PSS), and moderately in polymyositis or dermatomyositis (PM/DM) and mixed connective tissue disease (MCTD)]. These results were in sharp contrast with the finding that p14 is always at a highly elevated level but little p8 is present in the sera of cystic fibrosis (CF) patients [Bruggen et al. (1988) Nature 331, 570). | |
| 2167186 | Stimulation of neutrophil elastase and myeloperoxidase release by IgG fragments. | 1990 Aug | Human leucocyte elastase (HLE) cleaves IgG into Fab and Fc fragments. The Fc fragment bears an elastase-specific antigen and has previously been reported to be found in synovial fluid during rheumatoid arthritis. In addition, biological activity of elastase-specific Fc fragments has been described in modulating granulocyte oxidative metabolism. To investigate further regulatory effects of the elastase-induced IgG cleavage products, we tested the elastase and myeloperoxidase release of granulocytes. IgG fragments induce no enzyme release of unstimulated neutrophils. But elastase and myeloperoxidase release of cytochalasin b/FMLP-treated neutrophils is stimulated in a dose-dependent manner by the Fab fragments. The extent of stimulation depends on stimulus concentration and is at its maximum for low (e.g. 2.5 x 10(-8) M) FMLP concentration. Ten nanomoles Fab/4 x 10(6) PMN augment elastase release to 206% and myeloperoxidase release to 155% after pre-stimulation with 2.5 x 10(-8) M FMLP. Fc fragments stimulate elastase release to 162% but no MPO release. Untreated IgG1 and analog Fab and Fc fragments produced by papain cleavage react similarly. Elastase-generated IgG fragments may therefore up-regulate their concentration by simulating elastase release. The concomitantly stimulated release of myeloperoxidase may influence bactericidal activity and termination of oxidative burst. | |
| 2816986 | Dissimilar fatty acid composition of standard rat chow. | 1989 Nov | The lower incidence of coronary heart disease in populations consuming polyunsaturated fatty acids has spurred interest in the possible cardioprotective nature of these fatty acids. Furthermore, the source of dietary fats may modify the natural history of some chronic inflammatory disorders such as rheumatoid arthritis and systemic lupus erythematosus. Some studies examining these issues have involved animals fed a standard chow diet to which the desired fatty acids were added. Our observation that two lots of standard rat chow varied considerably in fatty acid composition, prompted us to analyze two additional standard rat chow lots for fatty acid composition. Each lot was extracted and fatty acid chain length determined by gas chromatography with the percentage of total fatty acids determined by integration. A wide variation in the total saturated (27.4-42.1%), monounsaturated (8.3-30.9%), omega 6 (17.2-44.2%), and omega 3 (3.8-11.2%) fatty acids was observed. By one-way analysis of variance, significant differences (p less than 0.025) between the various lots were observed for total saturated, monounsaturated, and omega 6 fatty acid groups. These findings suggest that fatty acid composition of standard rat chow is not similar. If the baseline fatty acid composition is critical to the experimental design, custom chow diets should be used. | |
| 2459252 | Preparative isolation of p67, A, B, B' and D from nRNP/Sm and Sm antigens by reverse-phase | 1988 Oct 4 | The p67 (67 kDa) and A (33 kDa) polypeptides of nRNP/Sm antigen and the B, B' (28 and 29 kda) and D (16 kDa) polypeptides of 'free' Sm antigen were isolated and used in enzyme-linked immunoadsorbent assays (ELISA) for human autoantibodies. ELISA specificity was demonstrated using monoclonal antibodies. The ELISA using HPLC-purified polypeptides was found to be more sensitive than immunoblotting for detecting antibody. 86% of sera with precipitating anti-nRNP antibodies were positive in the ELISA, as were all sera with precipitating anti-Sm antibodies. Patients with rheumatoid arthritis (RA), Sjögrens syndrome (SS) and undifferentiated connective tissue disease (UCTD) had low levels of anti-p67 with a prevalence 11.6% and 18%, respectively, whilst patients with systemic lupus erythematosus (SLE) and mixed connective tissue disease (MCTD) had high levels and prevalence rates of 55.2% and 80%, respectively. Anti-B or anti-D antibodies were detected at high levels in SLE (prevalence 30%) but were found rarely in UCTD and MCTD (prevalence 7% and 10%) and not at all in RA or SS sera. | |
| 3370569 | Unusual clustering of diseases in a Canadian Old Colony (Chortitza) Mennonite kindred and | 1988 Jun 1 | We investigated a large Old Colony (Chortitza) Mennonite kindred with branches across Canada. Six generations of the kindred were traced. There was intermarriage among numerous family members. Insulin-dependent diabetes mellitus (IDDM) was identified in 10 members; all 7 living patients were found to carry the immunogenetic marker HLA-DR4. Nine other close relatives had disorders of carbohydrate metabolism, including gestational diabetes mellitus and non-insulin-dependent diabetes mellitus progressing to insulin use. Ten other relatives had autoimmune diseases, including rheumatoid arthritis, hyperthyroidism, hypothyroidism and multiple sclerosis. Cases of Alport's syndrome, congenital malformations, inborn errors of metabolism and unusual malignant diseases were also found in the kindred. In the small Alberta community in which the kindred was ascertained there were people of Old Colony Mennonite descent with genetic conditions such as Gilles de la Tourette's syndrome and congenital malformations, including congenital heart disease. This kindred represents the largest reported familial aggregation of IDDM. This disease and other disorders of carbohydrate metabolism occur in the context of a strong familial predisposition to autoimmune disease. Study of this family may permit empiric testing of proposed models of inheritance of diseases of complex origin such as IDDM. We report this Old Colony (Chortitza) Mennonite community because it is one of the settlements populated by this religious and genetic isolate, which extends across Canada and Central and South America and affords opportunities for the study of both common and rare inherited diseases. | |
| 3075460 | Routine testing for antinuclear antibodies: a comparison of immunofluorescence, counterimm | 1988 Apr | We compared the classical immunofluorescence test (IFT) and counterimmunoelectrophoresis method (CIE) with the new immunoblotting technique (IBT) for the detection of antinuclear antibodies (ANA). Sera from 200 patients were tested in all three assays. Patients were classified as having either rheumatic disease including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), mixed connective tissue disease (MCTD), primary Raynaud's phenomenon or nonrheumatic disease. Within these broad categories, we observed that IFT and IBT showed a more or less comparable sensitivity and specificity (IFT: 0.54 and 0.82, respectively; IBT: 0.39 and 0.79, respectively). The CIE method combines a high specificity (0.99) with an extremely low sensitivity (0.08). By combining positive results obtained by IFT and IBT, a higher specificity (0.97) but a diminished sensitivity (0.24) is obtained. As IBT allows simultaneous discrimination between ANA of different specificities, we also tested for a correlation between the presence of anti-Sm, anti-RNP and anti-SS-B and the disease category. Only anti-SS-B discriminated significantly between rheumatic- and nonrheumatic disease. Anti-RNP was found in 50% of the SLE patients and in 50% of the MCTD patients; anti-Sm in 17% of the SLE patients and 25% of the MCTD patients. Anti-SS-B was found in 33% of the SLE patients. However, predictive rates of these ANA were low: 0.37 (anti-RNP), 0.67 (anti-Sm) and 0.43 (anti-SS-B). We conclude that from a practical point of view IFT is the preferable assay to screen for the presence of ANA. To characterize ANA specificities, however, the IBT is far superior to the CIE technique. | |
| 2881198 | [Enzymuria and kidney diseases in childhood]. | 1986 Dec | Urinary enzyme excretion and proteinuria were studied in 316 children with different underlying diseases. Activities on N-acetyl-beta-D-glucosaminidase and alanine aminopeptidase decreased progressively with age in the urine of 66 healthy prematures, newborns, infants or children. In 51 children with nephrotic syndrome, tubulopathies or chronic renal failure, excretion of NAG and AAP rose 3 to 30 fold. Contrary to molecular weight dependent protein analysis, determination of enzymuria did not allow to differentiate between glomerular and tubular disorders. After renal transplantation, 31 out of 52 children had a pathological enzymuria. NAG and AAP were more frequently elevated during treatment with cyclosporine A (21/29), than with azathioprine (10/23). The influence of nephrotoxic drugs upon enzymuria was documented in 14 children with cystic fibrosis or septicaemia treated with tobramycin. Activities of NAG and AAP rose transiently, whereas proteinuria remained almost unchanged. Only three out of 45 children receiving nonsteroidal antiinflammatory drug therapy for juvenile rheumatoid arthritis or spondylarthritis showed a pathological increase in enzymuria. Mean urinary NAG and AAP excretion in 154 children with insulin dependent diabetes mellitus were not different from controls and were unrelated to either duration of disease or HbA1 concentration. The determinations of urinary enzymes as non-invasive tests of renal integrity in medicine and toxicology provide a very sensitive indicator of renal damage. The assays of NAG and AAP have proven to be most valuable; however, due to a lack of specificity for the type and origin of renal dysfunction, these urinary enzyme assays are most useful when carried out in conjunction with electrophoretic analyses of proteinuria. | |
| 2940667 | Drug-associated glomerulopathies. | 1986 | The renal glomeruli are vulnerable to injury by a number of drugs and other toxic agents. These agents may lead to damage by one of two basic mechanisms: direct, dose-related toxic injury; indirect, immunologically mediated injury, largely dose-independent. Proteinuria is the simplest and most important functional indicator of glomerular injury. It occurs almost immediately in direct toxic injury, but there is a latent period of weeks to months with immunologically mediated processes. Of the two mechanisms, the second is by far the more common in clinical settings. The best studied experimental agent causing direct toxic injury is the aminonucleoside of puromycin. Clinically, perhaps the most important agent is Cyclosporine A. Although this agent is usually thought of primarily as a tubular toxin, it is capable of giving rise to a microangiopathic glomerular lesion similar to that in the hemolytic uremic syndrome. The classic model for immunologic glomerular lesion is Heymann nephritis, which produces a membranous glomerulopathy. Clinically, most drug mediated glomerulopathies also take the form of a membranous nephropathy, usually with a frank nephrotic syndrome. Among the more common offenders are penicillamine, gold salts used in rheumatoid arthritis, and captopril used in hypertension. The other common type of drug-related glomerulopathy occurs as part of a lupus-like syndrome induced by a variety of drugs, including hydralazine, procainamide, and penicillamine. All of these give rise to a variety of antibodies, most prominently antinuclear antibodies, and in the more severe cases there may be lupus-like glomerular lesions as well. | |
| 1645944 | Calcium channel autoantibodies in the Lambert-Eaton myasthenic syndrome. | 1991 Mar | We have tested 36 patients with the Lambert-Eaton myasthenic syndrome for serum antibodies to voltage-gated calcium channels by using an immunoprecipitation assay with [125I] omega-conotoxin-labeled voltage-gated calcium channels extracted from a human neuroblastoma cell line, SKN-SH. Forty-four percent of these patients had significant levels of antibody (30-1,466 pM) compared with healthy control individuals (less than 15 pM). The incidence of positive sera in patients without associated small cell lung carcinoma (61%) was greater than in those patients with small cell lung carcinoma (28%). Results correlated strongly with results obtained using voltage-gated calcium channels extracted from the small cell lung carcinoma line, MAR5. Anti-voltage-gated calcium channel antibody titers did not correlate with disease severity across individuals, but longitudinal studies in 2 patients receiving immunosuppressive therapy showed a clear inverse relation between antibody titer and an electromyographic index of disease severity. The incidence of positive sera among patients with other neurological disorders was not significant, but 8 of 12 patients with rheumatoid arthritis or systemic lupus erythematosus had raised titers (30-82 pM). We conclude that the antibodies detected in this assay are heterogeneous and that some of them are likely to be implicated in this disorder of neuromuscular transmission. The assay should prove useful as an additional diagnostic aid in patients with Lambert-Eaton myasthenic syndrome. | |
| 2359977 | Ulcer disease among geriatric inpatients with positive faecal occult blood test and/or iro | 1990 May | The purpose of this study was to investigate the prevalence and type of lesions in the upper gastrointestinal tract and to identify characteristics associated with ulcer disease among geriatric inpatients with positive faecal occult blood test and/or iron deficiency anaemia. Two thousand five hundred and four patients aged 60-98 (mean, 82) years admitted to a geriatric clinic for rehabilitation were screened by faecal occult blood test, for B-haemoglobin, and, in a case of anaemia, analyses of serum levels of mean corpuscular volume, mean corpuscular haemoglobin concentration, iron, and total iron-binding capacity. One hundred and seventy patients were included in the study. A high prevalence of ulcer disease (22%) was found. Significantly higher proportions of non-steroidal anti-inflammatory drugs and steroid users and of patients with rheumatoid arthritis and osteoarthrosis were found among ulcer patients than among patients without ulcerative upper gastrointestinal lesions. The clinical picture of ulcer disease differed from the classic presentation: abdominal pain occurred in only 7 of 38 patients (18%), whereas appetite and weight loss and nausea/vomiting were common. It is important to be aware of the high prevalence and the clinical picture of ulcer disease among geriatric inpatients with iron deficiency anaemia and/or occult gastrointestinal bleeding. | |
| 2323816 | Mycoplasma fermentans-derived high-molecular-weight material induces interleukin-6 release | 1990 May | A Mycoplasma fermentans-derived high-molecular-weight material (MDHM) is described which causes differentiation of concanavalin A-stimulated CBA/J or C57BL/6 mouse thymocytes to cytolytic effector T cells (CTLs). The effect of MDHM was inhibited by addition of monoclonal anti-interleukin-6 (IL-6) antibody. It could also be abolished after removal of adherent cells. However, adherent cell-depleted thymocytes could still form CTLs after addition of IL-6. The action of MDHM could thus be explained by the capacity of MDHM to stimulate IL-6 release from adherent cells. MDHM was active on macrophages from CBA/J and C3H/HeJ endotoxin nonresponder mice and was also capable of stimulating IL-6 release from human monocytes. On gel chromatography, MDHM had an apparent molecular size of 1.5 x 10(6) daltons. Treatment with RNase and DNase had no effect on either size or biological activity. Proteinase K did not abolish activity but reduced the apparent molecular size of MDHM. MDHM production by M. fermentans required either coculture with eucaryotic cell lines in RPMI 1640 medium with fetal calf serum or addition of eucaryotic cell sonic extracts to this medium. The biological activity of MDHM is not identical to that of a mitogen for murine spleen cells derived from M. arthritidis; MDHM caused only slight proliferation in this system compared with the mitogen from M. arthritidis, and the latter did not elicit IL-6 release from macrophages. The results are discussed in relation to mycoplasmas as putative etiological agents for rheumatoid arthritis, since high IL-6 titers were reported for synovial fluid from patients with this disease. | |
| 2451272 | Expression of platelet-derived growth factor receptors is induced on connective tissue cel | 1988 Mar | The tissue distribution of the receptor for platelet-derived growth factor (PDGF) was investigated by immunohistochemistry on frozen sections from normal and inflamed synovial tissue using monoclonal antibodies to the receptor. Non-inflamed synovial tissue showed no staining, indicating that PDGF receptor expression is low or absent in normal tissue. In contrast, tissue from synovitis with prominent neovascularization showed a strong staining in the tunica media of the proliferating blood vessels as well as on connective tissue cells in the stroma. Tissue from synovitis with prominent proliferation of synovial lining showed intense staining for PDGF receptors in fibroblast-like cells of the lining and a less intense staining on vascular and connective tissue cells deeper in the stroma. Staining for PDGF receptors was also intense in the pannus tissue close to infiltrated bone and cartilage. In all these forms of synovitis, PDGF receptor staining was associated with increased HLA-DR staining and infiltration of macrophages and T lymphocytes. The finding that PDGF receptor expression is induced in conjunction with the chronic synovial inflammation associated with rheumatoid arthritis and some other forms of arthritides suggests that PDGF may play a role in the stimulation of mesenchymal cell proliferation that often accompanies chronic inflammatory disease. | |
| 3795038 | Differential effect of plasma protein binding of bupivacaine on its in vivo transfer into | 1986 Dec | The effect of plasma protein binding of bupivacaine on its transfer into brain and salivary gland was studied using bovine serum albumin, human alpha 1-acid glycoprotein (AAG) and human serum. The in vivo brain extraction and salivary gland extraction of [3H] bupivacaine relative to [14C]butanol were determined with an intracarotid injection technique used on rats. The brain extraction varied inversely with the bovine serum albumin (0-7.5%) and AAG (0-3.0 mg/ml) concentrations. The salivary extraction only slightly varied inversely with the AAG concentration, whereas no significant effects of bovine albumin binding on salivary gland uptake were observed. The in vivo percentage of exchangeable drug in brain or salivary gland capillaries was severalfold greater than the in vitro percentage of unbound drug. The percent values of free drug, brain exchangeable drug and salivary exchangeable drug were 12 +/- 1, 81 +/- 7 and 93 +/- 18% for umbilical cord serum, 8.6 +/- 1.1, 73 +/- 6 and 103 +/- 3% for normal human serum, 5.9 +/- 0.5, 60 +/- 4 and 89 +/- 3% for serum of rheumatoid arthritis patients and 5.0 +/- 0.2, 45 +/- 2 and 83 +/- 3% for serum of metastatic cancer patients. These data indicate that bupivacaine is not transported through the brain capillary wall, i.e., the blood-brain barrier, from the bovine albumin-bound pool, but bupivacaine is partially available for transfer from the circulating AAG-bound pool. However, both bovine albumin-bound and AAG-bound bupivacaine are readily available for transport through salivary gland capillaries.(ABSTRACT TRUNCATED AT 250 WORDS) | |
| 2011111 | Neuro-ocular Lyme borreliosis. | 1991 Feb | Any patient who has a Bell's palsy (unilateral or bilateral), aseptic meningitis, chronic fatigue syndrome, atypical radiculoneuropathy, presenile dementia, atypical myopathy, or symptoms of atypical rheumatoid arthritis should be asked specifically about the following: visits to highly endemic areas, any known tick bites, any skin lesion suggestive of erythema migrans, any history of palpitations or of prior Bell's palsy, aching in joints (especially the knees), paresthesias, chronic fatigue and depression, forgetfulness, and eye problems. Any patient showing a chronic iritis with posterior synechiae, vitritis in one or both eyes, an atypical pars planitis-like syndrome, big blind spot syndrome, and swollen or hyperemic optic discs should be asked the same questions. The physician should send one red-top tube of blood containing 2 to 3 ml serum to Microbiology Reference Laboratory, 10703 Progress Way, Cypress, CA 90630-4714, requesting a Lyme/treponemal panel. For $90 the patient will receive an RPR test with titer, serum FTA-ABS test, serum Lyme IFA IgG and IgM, and a serum Lyme ELISA test. If these tests are within normal limits and the physician is still suspicious, a Western blot can be ordered on serum. A green top tube with fresh white blood cells sent out by overnight express on a Monday or Tuesday will produce a Lyme PCR and a lymphocyte stimulation test. Finally, R.K. Porschen, director of MRL Laboratory, will provide information on the urine antigen test on an investigational basis. A careful history with emphasis on the specific questions noted above, a complete neuro-ophthalmological and physical examination ruling out other causative problems, and the laboratory studies here discussed will usually provide sufficient data to choose therapy. Much further active research into Lyme borreliosis is an important priority in medicine. | |
| 2060177 | Statural growth and skeletal maturation in rheumatic prepubertal children treated with a t | 1991 Jan | Deflazacort, a new glucocorticoid (DFZ) which has recently become available, is known to have lower adverse effects on the skeletal metabolism and is expected to inhibit growth to a lesser extent in long-term treated children than earlier cortisone analogues. With the aim of verifying this hypothesis a multicenter study was planned to compare the effects of deflazacort and prednisone on linear growth and skeletal maturation in a group of prepubertal children requiring chronic steroid therapy. The data presented in this interim analysis refer to 24 children (11 females and 13 males ranging in age from 2.4 to 11.8 yrs) with rheumatoid arthritis (18), systemic lupus erythematosus (4) or dermatomyositis, selected from the total sample of 65 subjects included in the trial. They were randomly allocated to DFZ or PDN treatment and received the minimum effective dose of either steroid for at least 6 months per year. Longitudinal height measurements were obtained with standard instruments and techniques, and the bone age was assessed according to Greulich and Pyle. The following indicators of growth retardation were considered: bone age delay (difference between bone age and chronological age), statural age delay (statural age, with respect to the 50th percentile minus the chronological age) and statural age loss (statural age with respect to the individual height percentile at the first observation minus the chronological age).(ABSTRACT TRUNCATED AT 250 WORDS) |