Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
10828318 Inhibitors of the enzyme purine nucleoside phosphorylase as potential therapy for psoriasi 2000 Jun Purine nucleoside phosphorylase (PNP) is one of the enzymes comprising the purine salvage pathway , and is responsible for the catalysis of the reversible phosphorolytic cleavage of purine ribonucleosides and 2'-deoxyribonucleosides. The pivotal role of PNP in T-cell proliferation has been demonstrated in patients with inherited PNP deficiency, where T-cell levels may be 1-3% of normal. This observation helped establish the critical role of PNP in T-cells and provided a rationale for developing inhibitors of PNP. Inhibitors of PNP may be useful for treating a variety of T-cell related autoimmune diseases including psoriasis, rheumatoid arthritis and Crohn s disease and T-cell cancers. In this manuscript, the x-ray crystal structure of the PNP enzyme is described. Results of a structure-based drug design program aimed at designing small-molecule inhibitors of PNP are also described. Of the many classes of compounds synthesized, studied and reviewed, only one, the 3-pyridinylmethyl-9-deazaguanine (BCX-34, 39) analog has been used in clinical trials. Both topical and oral formulations of BCX-34 were studied in psoriatic patients and the results of these clinical trials are described.
10791620 Maximal isometric muscle strength: normative values and gender-specific relation to age. 2000 To date, there have been very few studies on the age dependence of maximal isometric muscle strength (MIMS) in healthy subjects aged 20-80 years, based upon measurements of a large number of functional muscle groups (FMGs). Using a hand-held pull gauge it is possible to measure MIMS of nearly every FMG. The objectives of this study were to obtain normative values for MIMS, to evaluate differences in MIMS in relation to gender and body side and to compare the age dependence of muscle strength between women and men. In a convenience sample of 290 healthy women (aged 20-82 years) and 253 men (aged 21-79 years), MIMS of 51 FMGs was measured. For each FMG the age dependence of MIMS was depicted, side and gender specific, as percentile curves and was analysed using linear quantile regression analysis. MIMS was found to be significantly higher in men than in women and higher on the right than on the left side. A biphasic model with linear equations for strength medians was derived for each gender. The age at transition from phase 1 to phase 2 was 55 years (SD 8) for women and 49 years (SD 13) for men. During phase 1, MIMS did not decrease significantly. During phase 2, MIMS decreased in all FMGs in both genders with a steeper slope in women (-0.92) than in men (-0.63). The age dependence of MIMS differed significantly between women and men. The present study gives gender-specific equations which enable one to calculate normative values for MIMS, as measured with a pull gauge, based upon age. These normative values will allow an objective assessment of patients with diminished muscle strength as, for example, in myositis, rheumatoid arthritis and nerve root compression syndromes or in the elderly.
10599674 Episcleritis in childhood. 1999 Dec OBJECTIVE: To describe the characteristics and systemic disease associations of episcleritis in childhood. DESIGN: Retrospective, observational case series. PARTICIPANTS: Twelve children diagnosed with episcleritis between July 1981 and June 1998. METHODS/TESTING: Complete eye and systemic evaluations. MAIN OUTCOME MEASURES: Characteristics of episcleritis and presence and nature of concurrent systemic disease. RESULTS: The 12 children (10 boys and 2 girls) ranged in age from 13 months to 16 years. Five children had bilateral simple episcleritis, one had bilateral nodular episcleritis, and six had unilateral simple episcleritis. The eye examination was otherwise normal and recovery was uneventful in all cases. Six of the nine children older than 5 years of age had one of the following rheumatologic diseases: systemic lupus erythematosus, juvenile rheumatoid arthritis, spondyloarthropathy, inflammatory bowel disease, rheumatic fever, or polyarteritis nodosa. All three children younger than 5 years of age had simple episcleritis, an antecedent viral illness, and presented within 2 months of each other. CONCLUSIONS: Episcleritis is a rare occurrence in childhood, especially in children younger than 5 years of age. In older children, it is frequently associated with rheumatologic disease.
10455416 Augmentation of natural immunity to a pro-inflammatory cytokine (TNF-alpha) by targeted DN 1999 Jun TNF-alpha is thought to be a key pro-inflammatory cytokine in T cell-mediated autoimmune diseases, particularly in rheumatoid arthritis (RA) and multiple sclerosis (MS). Experimental autoimmune encephalomyelitis (EAE) serves as an animal model for MS. The current study observes a notable TNF-alpha-specific antibody titer generated during the course of EAE, apparently not sufficient to prevent the development of disease. Administration of TNF-alpha-naked DNA vaccine enhanced the production of TNF-alpha-specific antibody titer and conferred EAE resistance. These antibodies were found to be neutralizing in vitro and capable of inhibiting the development of disease when transferred to other EAE rats. Thus, modulation of EAE with TNF-alpha DNA vaccines enhances the regulation of natural immunity to a self pro-inflammatory cytokine and provides a tool by which the immune system is encouraged to elicit anti-self protective immunity to restrain its own harmful reactivity when such a response is needed.
10451123 Simultaneous analysis of nitrite, nitrate and the nicotinamide nucleotides by capillary el 1999 Jul A simple but rapid capillary electrophoresis method was developed for the measurement of nitrite and nitrate in human extracellular fluids and other aqueous solutions. The capabilities of the method were demonstrated by the measurement of endogenous nitrite and nitrate in plasma and serum samples from healthy volunteers, and serum and synovial fluid samples from rheumatoid arthritis patients. Furthermore, this method was used to simultaneously measure nicotinamide adenine dinucleotide, reduced (NADH), nicotinamide adenine dinucleotide (NAD+), nitrite, and nitrate, when studying the nitrite reductase activity of xanthine oxidase. The stability of nitrite was also investigated and it was found that when whole blood was spiked with nitrite and then processed, the nitrite was more stable in the plasma than in the serum. Our findings may help to explain the variations in basal nitrite concentrations reported in the literature.
10415615 IL-15/IL-15R alpha intracellular trafficking in human cells and protection from apoptosis. 1999 Jun 22 IL-15 is an immunostimulatory cytokine sharing with IL-2 the IL-2R beta gamma complex. In vivo, IL-15 detection in synovial fluids has been associated with the development of rheumatoid arthritis. A debate exists as to whether IL-15 has the potential to be secreted in meaningful amounts or to act as a pericellular cytokine. Our data show (1) the presence of two IL-15 isoforms displaying signal peptides of different length and the capacity to be secreted restricted to the isoform bearing the longer one; (2) in cells expressing the two isoforms, the existence of different nuclear localization and intracellular trafficking of IL-15 and IL-15R alpha; and (3) an intercellular microcirculation of IL-15, not detectable with ELISA kits, but displaying a role as an anti-apoptotic factor able to induce the deflection of the TNFR associated factor 2 (TRAF) to IL-15R alpha. Our data point to a juxtacrine mechanism of action of IL-15 and suggest a role for IL-15/IL-15R alpha in the regulation of apoptosis.
10402066 Should dehydroepiandrosterone replacement therapy be provided with glucocorticoids? 1999 Jun Adrenocorticotrophic hormone (ACTH) induces the concomitant secretion of glucocorticoids (GC) and dehydroepiandrosterone (DHEA) from the adrenal cortex. Whereas GC are catabolic, DHEA is anabolic. Long-term GC administration may result in some deleterious side-effects, such as muscular weakness, atrophy and necrosis, diabetes, fattiness, osteopenia, osteoporosis and avascular necrosis and susceptibility to infections. DHEA ameliorates some deleterious effects of GC, such as diabetes, amino acid deamination, fattiness, hypertension and susceptibility to viraemia. By its anabolic effects in muscles, bones and endothelium, DHEA may diminish the severity of GC-induced myopathy, osteopenia, osteoporosis and avascular necrosis. The natural concomitant secretion of DHEA with GC probably enables the latter to protect the body from ill-effects of stress without exerting their deleterious potency. DHEA secretion diminishes during aging and severe or chronic diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Anti-inflammatory and immunosuppressive effects of GC and androgens, including DHEA, are now well established. On the other hand, administration of GC inhibits ACTH secretion, involutes the adrenal cortex and results in further DHEA deficiency, particularly harmful in chronic autoimmune diseases (i.e. RA, SLE). Therefore, the deleterious side-effects of chronic administration of GC emerges from both their direct catabolic activity and the suppression of DHEA production. Whereas, in males, most androgens come from the testes, in females, under GC supplementation, DHEA deficiency leads to nullification of the androgen-dependent anabolism, leaving them exposed to the GC-catabolic effects to a larger extent. The viewpoint presented here claims that under chronic GC supplementation, DHEA replacement therapy may reduce damage caused by GC administration.
10370735 Different strategies in the laboratory diagnosis of autoimmune disease: immunofluorescence 1999 Mar We investigated the clinical utility of different strategies for antinuclear antibodies (ANA) and antibodies to extractable nuclear antigens (ENA) testing. All requests for ANA and ENA (n = 485) in a 20-week period were tested by immunofluorescence (FANA) and immunodiffusion (strategy 1), enzyme-linked immunosorbent assay (ELISA) techniques (strategy 2) or a combination of FANA and ELISA (strategy 3). Results of strategy 1 were positive by FANA in 8% (by immunodiffusion in 2%). By ELISA, 11% of the samples tested positive. In 12% (n = 60) of the cases the two strategies did not agree. The positive predictive value (PPV) for autoimmune disease of strategy 1 was significantly higher than that for strategy 2, but after exclusion of rheumatoid arthritis this difference was abolished. In strategy 2 reagent costs were high but working time comparably shorter. With strategy 3 PPV results were not better, whereas costs and working time were higher. The most frequently occurring reasons for ANA/ENA test requests were: joint symptoms (37%), follow up (30%) or abnormal laboratory result (7%). In a survey of the clinicians 66% replied that the test result did not have any consequences, irrespective of the result or the strategy used. We conclude that FANA and immunodiffusion are superior to ELISA techniques. However, the clinical value of ANA/ENA testing is low and more selective test ordering is strongly recommended.
10369953 Radioiodine uptake in inactive pulmonary tuberculosis. 1999 Jun Radioiodine may accumulate at sites of inflammation or infection. We have seen such accumulation in six thyroid cancer patients with a history of previously treated pulmonary tuberculosis. We also review the causes of false-positive radioiodine uptake in lung infection/inflammation. Eight foci of radioiodine uptake were seen on six iodine-123 diagnostic scans. In three foci, the uptake was focal and indistinguishable from thyroid cancer pulmonary metastases from thyroid cancer. In the remaining foci, the uptake appeared nonsegmental, linear or lobar, suggesting a false-positive finding. The uptake was unchanged, variable in appearance or non-persistent on follow-up scans and less extensive than the fibrocystic changes seen on chest radiographs. In the two patients studied, thyroid hormone level did not affect the radioiodine lung uptake and there was congruent gallium-67 uptake. None of the patients had any evidence of thyroid cancer recurrence or of reactivation of tuberculosis and only two patients had chronic intermittent chest symptoms. Severe bronchiectasis, active tuberculosis, acute bronchitis, respiratory bronchiolitis, rheumatoid arthritis-associated lung disease and fungal infection such as Allescheria boydii and aspergillosis can lead to different patterns of radioiodine chest uptake mimicking pulmonary metastases. Pulmonary scarring secondary to tuberculosis may predispose to localized radioiodine accumulation even in the absence of clinically evident active infection. False-positive radioiodine uptake due to pulmonary infection/inflammation should be considered in thyroid cancer patients prior to the diagnosis of pulmonary metastases.
9917668 Femoral component failure in hybrid total knee arthroplasty. 1998 Nov From 1986 to 1991, 74 consecutive hybrid total knee arthroplasties (in 65 patients) of a single design were performed at the authors' institution. Seven patients (eight knees) died with well functioning replacements during the surveillance period. One patient refused to participate in any followup efforts because of billing disputes. This left 65 total knee arthroplasties (57 patients) for review. There were 35 men and 22 women with an average age of 60 years (range, 27-83 years) at the time of arthroplasty. The underlying diagnosis was osteoarthritis in 46 knees, rheumatoid arthritis in six knees, and other in four knees. The average length of followup was 7.4 years (range, 5-10 years), and no patients were lost to followup. The Knee Society scores improved from an average of 37 preoperatively to 84 at latest followup. The functional score improved from 49 to 69 at latest followup. Ten (13.8%) knees required revision surgery. Eight of the nine knees that were revised had femoral component problems, including a loose component in six and a fractured component in two. One knee was revised for polyethylene wear with secondary osteolysis and one was revised elsewhere in which the operative details are unknown. The implant survival to revision at 5 years was 89% and 85% at final followup. Femoral component fixation in hybrid total knee arthroplasty in unreliable with this component design. In light of the excellent 10- to 15-year results of cemented condylar knee designs it is thought that hybrid fixation should be abandoned.
9855235 Epidemiology of acute vertebral osteomyelitis in Denmark: 137 cases in Denmark 1978-1982, 1998 Oct We studied the epidemiology of acute, non-tuberculous, hematogenous vertebral osteomyelitis in Denmark during 1978-1982. 137 patients fulfilled the criteria for acute vertebral osteomyelitis. The incidence was 5/mill/year. There were no cases in the age group 20-29 years. The highest incidence was between 60-69 years (18/mill/year). The prevalence was 15 cases. The mean duration of the disease was 7 months. The lumbar spine was affected in 59%, the thoracic spine in 33% and the cervical spine in 8% of the cases. Insulin-dependent diabetes and treatment with systemic corticosteroids seemed to be significant risk factors, but not rheumatoid arthritis and abuse of alcohol or intravenous drugs. We found no demographic variables of importance for the incidence. In 46%, a primary focus was identified, urinary tract infection being the commonest. According to the National Patient Register 1991-1993, the relative number of reported patients with vertebral osteomyelitis had increased in the age group 20-49 years, compared to 1978-1982, but the incidence was highest in the group aged 60-79 years.
9834131 Proteolytic cleavage of ICAM-1 by human neutrophil elastase. 1998 Dec 1 Human leukocyte elastase (HLE) participates in tissue destruction in a number of inflammatory disorders, including rheumatoid arthritis and cystic fibrosis. Since HLE has been shown to bind to Mac-1, and ICAM-1 plays a key role during the recruitment and the activation of leukocytes at inflamed sites, we investigated the capacity of HLE to cleave ICAM-1. Flow-cytometric analyses showed a dose-dependent cleavage of ICAM-1 by HLE on different human cell lines. The cleavage was completely inhibited by alpha1-antitrypsin, a natural HLE protease inhibitor. The ability of HLE to degrade ICAM-1 was further confirmed by electrophoretic analysis using a soluble form of ICAM-1 (D1-D5). Enzymatic removal of N-linked glycosylation did not significantly modulate ICAM-1 cleavage by HLE, while removal of sialic acid residues partially reduced the sensitivity of ICAM-1 to HLE. We further showed that sputum of cystic fibrosis patients contains high levels of HLE activity capable of cleavage of cell surface ICAM-1. The cleavage induced by incubation of cells with the sputum sample was totally inhibited by alpha1-antitrypsin and the specific peptidic HLE inhibitor N-methoxysuccinyl-Ala-Ala-Pro-Val-chloromethylketone. Moreover, the cleavage of ICAM-1 was concomitant to that of CD4 at the surface of the same cell, at the same amplitude, and at all HLE concentrations. The capacity of HLE to modulate the expression of ICAM-1 on the surface of leukocytes by proteolytic cleavage brings support to the hypothesis that overproduction of HLE can cause severe immunologic lung disorders by affecting intercellular adhesion.
9795771 Identification of autoantigen epitopes in MHC class II transgenic mice. 1998 Aug MHC class II molecules function by selective binding of antigenic peptides, thereby both shaping the T-cell receptor (TCR) repertoire in the thymus and influencing presentation of immunogenic peptides to CD4+ T cells in the periphery. The strong association between a number of human autoimmune diseases (type 1 diabetes, rheumatoid arthritis, and multiple sclerosis) and certain HLA-DR/DQ alleles suggests that it may be possible to alter pathological autoimmune responses by deliberate introduction of autoantigenic peptides in a "tolerogenic" manner. Since there are likely to be differences in epitope selection and epitope spreading in different patients over time, this approach requires identification of all the immunogenic CD4+ T-cell epitopes (dominant, subdominant, or cryptic) of an autoantigen which elicit T-cell responses restricted to the HLA-DR/DQ alleles predisposing to these autoimmune diseases. This paper describes a new approach for the identification of immunogenic peptide epitopes of human autoantigenic proteins using HLA-DR and DQ transgenic mice. These mice are engineered to select a full TCR repertoire which can identify immunogenic peptide epitopes similar or identical to human subjects of the same HLA-DR/DQ genotype. This experimental system also allows comparison of autoantigenic immune responses restricted to disease-susceptible and disease-resistant HLA-DR/DQ alleles.
9790956 Induction of mitogen-inducible nuclear orphan receptor by interleukin 1 in human synovial 1998 Oct 9 High levels of interleukin 1 (IL-1) found in inflammatory diseases such as rheumatoid arthritis and periodontitis act on the local fibroblasts, resulting in an altered phenotype characterized by hyperplasia and the production of inflammatory mediators and destructive enzymes. The goal of this study was to identify genes induced as an early response to IL-1 in synovial and gingival fibroblasts which might play a regulatory role in the cascade of events leading to their activation. Using the technique of mRNA differential display, we have identified the mitogen-inducible nuclear orphan receptor (MINOR) as a gene up-regulated by IL-1 in human synovial and gingival fibroblasts. The rapid induction of both mRNA and DNA binding activity suggests that MINOR may play an important early role in regulating the response of fibroblasts to inflammation.
9721558 [Sarpogrelate hydrochloride for Raynaud's phenomenon of patients with collagen diseases]. 1998 Jun OBJECTIVE: To evaluate clinical efficacy of sarpogrelate hydrochloride (SPG), a novel 5HT2- serotonergic receptor antagonist, for Raynaud's phenomenon associated with collagen diseases. PATIENTS AND METHODS: Thirty two patients with collagen diseases such as scleroderma, mixed connective tissue disease, systemic lupus erythematosus, Sjögren's syndrome, and rheumatoid arthritis were enrolled. SPG (300mg/day) was administered for 8 weeks. Patients were asked to record the frequency of Raynaud's phenomenon and subjective symptoms in a diary, and evaluations were made in weeks 4 and 8 of treatment. Thermography and determination of whole blood serotonin levels were also conducted in some patients. RESULTS: The frequency and duration of Raynaud's phenomenon and subjective symptoms such as coldness and pain significantly improved in weeks 4 and 8 compared to the pre-treatment baseline. Thermography showed significantly improvements of skin temperature recovery rate following cold water loading after treatment with SPG. Epigastric distress was reported by 3 patients, but no other adverse reaction or abnormal changes in laboratory tests were observed. Whole blood serotonin levels per platelet increased significantly after treatment with SPG, suggesting that administration of SPG might inhibit activation of the platelets. CONCLUSION: A global improvement rate ("markedly improved" + " moderately improved") of 66% was obtained and SPG was regarded as safe in 85% of patients and useful or very useful in 82%. SPG is expected to be a useful new therapy for Raynaud's phenomenon in patients with collagen disease.
9719250 Combined hepatocellular and cholangiocellular carcinoma in a non-cirrhotic liver. 1998 Aug Combined hepatocellular (HCC) and cholangiocellular carcinoma (CCC) (mixed carcinoma) is a rare subtype of primary hepatic carcinoma. We report a case of mixed carcinoma that developed in a non-cirrhotic liver, in a patient who was serologically negative for both hepatitis B and C viruses. A 65-year-old Japanese woman with a 25-year history of chronic rheumatoid arthritis had been treated with steroids and anti-inflammatory drugs, and was diagnosed by ultrasonography with an asymptomatic solitary tumor in the right lobe of the liver. On computed tomography scan and hepatic arteriography, the tumor was well enhanced by contrast medium in the early phase. Based on the findings of elevated serum alpha-feto protein (AFP, 245 ng/ml) and normal carcino-embryonic antigen (CEA, 2.6 ng/ml) levels, a preoperative diagnosis of hepatocellular carcinoma was made. Right lobectomy of the liver was performed on January 7, 1997. Histological examination showed that the resected tumor consisted of combined CCC cells and HCC cells in an intermingled form, with CCC being far more dominant than HCC. The tumor was therefore determined to be a combined carcinoma, subclassified as intermingled type. This case appears to indicate that mixed type carcinoma developed in a non-cirrhotic liver, with CCC being dominant; such a finding is extremely unusual, based on previously published reports.
9619656 Clinical experience of rehabilitation therapists with chronic diseases: a quantitative app 1998 Apr OBJECTIVES: To provide an overview of the numbers of patients with selected chronic diseases treated by rehabilitation therapists (physical therapists, occupational therapists, exercise therapists and podiatrists). The study was performed to get quantitative information on the degree to which rehabilitation therapists are experienced in the treatment of chronically ill patients. METHODS: Secondary analyses were performed on several databases containing representative data on patients treated by rehabilitation therapists. Rates per 1000 patients in the populations of these rehabilitation therapists and 90% confidence intervals were computed for patients with the following diagnoses: ischaemic heart diseases, stroke, rheumatoid arthritis, osteoarthritis, osteoporosis, multiple sclerosis, Parkinson's disease, epilepsy, headache syndromes, COPD/asthma, diabetes mellitus and chronic back pain (the size of the latter group could only be assessed in physical therapy in primary care). RESULTS: The largest group of chronically ill patients treated by physical therapists in primary care are patients with chronic back pain (82 per 1000). Stroke patients are the most common chronically ill patients treated by physical therapists in institutional care (157 per 1000) and by occupational therapists in institutional (358 per 1000) and noninstitutional care (246 per 1000). These therapists also see a variety of other chronically ill patients. Exercise therapists and podiatrists treat less patients with the selected chronic diseases.
9286061 Models of mycoplasma respiratory and genital tract infections. 1997 Aug 8 Animal models for the study of human diseases must be replaced by in vitro methods, whenever possible. However, when critically evaluated, they remain indispensable for the solution of some specific problems in infectious diseases. These include the pathogenesis, the host response, as well as the study of antimicrobial agents and vaccines. Under these conditions animal models, which closely reflect the situation in man, are especially valuable. Two models may serve as "ideal" examples for the study of human diseases: firstly mouse typhoid for the study of systemic infections with Salmonella typhimurium. This model has been employed for many decades to examine various aspects of human typhoid fever. A second model is the experimental infection of hamsters with Mycoplasma pneumoniae as a model of local infection in the respiratory tract. Mycoplasma and ureaplasma infections of man are frequent, but rarely life threatening. Chick embryos, rats, hamsters, guinea pigs, and monkeys (rhesus monkeys and chimpanzees) are susceptible to experimental infection with M. pneumoniae. Some mouse strains are also colonized with M. pneumoniae after intranasal inoculation, but histopathological alterations similar to the hamster model have not been established in a reproducible way in mice. Hamsters have, therefore, been important for the evaluation of antibiotics and vaccines. Local immunity in the respiratory tract, the possible contribution of the immune response to disease pathogenesis, persistence of the organisms in the respiratory tract after clinical symptoms are cured by antibiotic therapy, and the role of cytokines in protection or disease pathogenesis remain interesting areas for future research, which could be addressed in animal models. The evaluation of the role of mycoplasmas and ureaplasmas in genital tract infections is by far more complex and even more difficult in AIDS and rheumatoid arthritis, because several species of mycoplasmas and Ureaplasma urealyticum can be isolated from a large proportion of healthy individuals. Furthermore, good models for the study of these infections are not available.
9236859 Angiogenesis: new aspects relating to its initiation and control. 1997 Jun Angiogenesis, the formation of new microvessels from parent microvessels, involves remodeling the basement membrane and interstitial extracellular matrix (ECM) using degrading proteases produced by the endothelial cells (ECs) and other adjacent cells, and the synthesis of ECM molecules by these cells. Degraded ECM releases previously bound heparin-binding cytokines (and growth factors) which are able to act as ligands to high-affinity receptors on various target cells, including ECs. The EC carries receptors for a number of cytokines which are produced by neighboring cells or released from the ECM and which can either induce or suppress the angiogenic phenotype of the EC. ECs are able to synthesize and secrete cytokines with auto- and paracrine effects. Angiogenesis, which virtually never occurs physiologically in adult tissues (except in the ovary, the endometrium and the placenta), is essential in wound healing and inflammation. Angiogenesis is, in fact, strictly controlled by a redundancy of pro- and anti-angiogenic paracrine peptide molecules, some of which have recently been described. The expression and synthesis of two distinct anti-angiogenic factors is, for example, controlled by the p53 tumor suppressor gene. In certain hypoxic conditions, chronic inflammatory diseases and syndromes, angiogenesis is of pathogenic and prognostic significance. Angiogenesis is, moreover, essential for the growth and metastatic spread of solid tumors. This indicates the potential for developing new therapeutic strategies not only for tumors but also in diseases such as rheumatoid arthritis, psoriasis, liver cirrhosis and diabetic retinopathy. Moreover, the therapeutic induction of angiogenesis in ischemic tissues using recombinant cytokines is also promising for clinical application. In fact, the first successful human gene therapy for stimulating angiogenesis has recently been reported.
9202590 The clinical importance of axillary lymphadenopathy detected on screening mammography. 1997 Jun The aim of this study was to determine the incidence and cause of axillary lymphadenopathy detected by screening mammography and to devise a management protocol for this pathology. In a retrospective study of 95,806 consecutive screening mammograms, 37 cases of 'pathological' axillary nodes were identified using two or more of the following criteria: size > 2 cm, replacement of fatty hilum, rounded shape and generalized increased density. In 16 cases with an additional mammographic abnormality, 12 had a mass (10 malignant and two benign) and four had suspicious calcification (all malignant). In 12 of these cases, the lymph nodes showed malignancy (75%). In 21 patients with lymphadenopathy alone on screening, six patients had a known underlying diagnosis and were not recalled from screening. The remaining 15 patients were recalled for further assessment including fine needle aspiration cytology (FNAC). The ultimate diagnosis was benign in 10 cases (48%)--six reactive changes, one healed granulomatous disease, one rheumatoid arthritis, one amyloid and one acute infection--and malignant in 11 cases (52%)--six non-Hodgkin's lymphoma, four metastatic carcinoma and one leukaemia. In conclusion, there is a high incidence of malignant nodal involvement in cases of screen detected lymphadenopathy (62% of cases in our series). We would advise that patients with lymphadenopathy as the sole finding on screening mammography and in whom there is no known underlying cause should undergo FNAC followed by excision biopsy. Fifty per cent of such patients in this study had underlying malignancy.