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ID PMID Title PublicationDate abstract
9844759 Inappropriate apoptosis of salivary and lacrimal gland epithelium of immunodeficient NOD-s 1998 Nov OBJECTIVE: The lesion is Sjögren's syndrome consists of lymphocytic infiltration and has a pathology characteristic of the potential apoptotic death of salivary gland secretory epithelial cells. To examine the role of the glandular epithelial cells in the pathogenesis of autoimmune exocrinopathy, we studied Fas and Fas ligand (FasL) expression and quantitated the levels of apoptosis in salivary and lacrimal glands from NOD and NOD-scid mice, an animal model that develops a Sjögren's syndrome-like pathology. METHODS: The parotid, submandibular and lacrimal tissues of NOD, NOD-scid, and BALB/c mice were evaluated by immunohistochemical analysis for the expression of Fas and FasL. Nuclear fragmentation of DNA from the epithelial cells of exocrine tissues was evaluated by the terminal UTP nucleotide end labeling method (TUNEL). Messenger RNA was isolated from 8 and 18 week old mice and was analyzed by the reverse transcription-polymerase chain reaction (RT-PCR) for the expression of Fas and FasL. RESULTS: We found suggestive evidence that apoptosis of the secretory epithelial cells occurs in both NOD and NOD-scid mice despite the lack of T- and B-lymphocytes in the latter. FasL mRNA and cell surface protein were expressed in salivary and lacrimal gland epithelial cells from 8 and 18 week old NOD, NOD-scid, and BALB/c mice. Fas protein and mRNA were expressed only in the exocrine glands from 18 week old NOD and NOD-scid mice. Glandular secretory epithelial cell apoptosis was elevated in both NOD and NOD-scid mice, however; there was little evidence of apoptosis in the control strain of BALB/c mice. CONCLUSION: These results suggest a potential apoptotic process dependent on Fas:FasL interactions occurring in NOD-scid glandular secretory epithelial cells in the absence of lymphocytic infiltration.
17657620 An analysis from clinico-epidemiological data of the principal adverse events from the COX 1998 The safety of the cyclo-oxygenase-2 (COX-2) selective NSAID, nimesulide, has been evaluated from information (a) in clinical trials in osteoarthritis that have been performed in Europe as well as in earlier pilot studies that were performed in patients with rheumatoid arthritis in the USA, and (b) in post-marketing studies (PMS) that have been performed by the manufacturer since the introduction of the drug in Europe and some South American countries. Upon analysis there have been clear indications of elevation of liver enzymes being related to the drug in 3/753 patients who were investigated in clinical trials in osteoarthritis. The results of the analysis of adverse drug reactions (ADRs) in patients with osteoarthritis (which is the principal indication for the drug) in PMS showed that the greatest number of these were in the skin and appendages, digestive system and organs wherein metabolic effects were manifest. There was a relatively low number of reports of gastrointestinal ulceration and haemorrhage, and these observations are in agreement with published experimental studies in humans and laboratory animals. Recent reports of ADRs in the liver in 25 patients were analysed in detail. In many of the cases there was evidence of confounding disease (e.g. cancer, prior liver damage) or prior or concurrent intake of known hepatotoxic NSAIDs (diclofenac, aspirin). Often elevations of liver enzymes above the laboratory norms are the only indication of liver injury and this in many cases is variable. The major cases of elevated liver enzymes and other liver changes have been in elderly patients.This first extensive analysis of ADRs from a COX-2 selective NSAID, nimesulide, indicates that there is a relatively low incidence of ADRs especially in the gastrointestinal tract, while those in the liver are within or below the general incidence with other NSAIDs.
11873872 Cross-reactive mechanism for the false elevation of free triiodothyronine in the patients 2001 Dec We report three cases of patients exhibiting a false elevation of serum free triiodothyronine (FT3) as a result of a cross-reaction with diclofenac. The first case is a 66-yr-old woman with a long history of rheumatoid arthritis (RA). The patient was receiving diclofenac for the treatment of her RA. The patient was subsequently diagnosed as having thyroid papillary adenocarcinoma and received a subtotal thyroidectomy. After the operation, the patient exhibited postoperative hypothyroidism except for a gradual elevation of FT3. The other two patients also exhibited an elevated serum FT3 level after the administration of diclofenac. Serum FT3 levels in these patients decreased to normal or below normal after diclofenac administration was discontinued. In the first case, the elimination of immunoglobulin from the sera using polyethylene glycol precipitation did not reduce the FT3 level. In our hospital, Vitros ECi (enhanced chemiluminescence enzyme immunoassay) system and Vitros FT3 kit were used for FT3 assay. The patient's FT3 levels were normal or below normal when they were measured using other FT3 kits. FT3 was also detected when diclofenac was dissolved in a phosphate buffered saline. Therefore, we concluded that a cross-reaction between FT3 and diclofenac was the mechanism causing the false elevation of FT3 in these patients.
11847486 Elevated levels of serum prolactin in patients with advanced multiple myeloma. 2001 BACKGROUND AND OBJECTIVE: The role of prolactin in immunoregulation and normal hemopoiesis is well known. However, prolactin also seems to be involved in the pathomechanism of malignancies and autoimmune diseases. Elevated serum prolactin levels were reported in patients with malignant lymphoma, colon and breast carcinoma, systemic lupus erythematosus and rheumatoid arthritis. Recently we demonstrated prolactin immunostaining in bone marrow cells of patients with multiple myeloma. DESIGN AND METHODS: Serum prolactin levels of 56 patients with multiple myeloma, as well as serum beta(2)-microglobulin, and interleukin-6 concentrations were determined in this study. RESULTS: Patients with advanced disease showed a significant increase in serum prolactin concentration, while patients with a clinical stage of I and II, and also control patients had normal values. The concentration of serum beta(2)-microglobulin and interleukin-6 changed in parallel with that of serum prolactin in patients with multiple myeloma. Determining serum prolactin levels several times during the disease process in a given patient clearly showed that the prolactin concentration was increasing during the disease progression. INTERPRETATION AND CONCLUSIONS: Our results indicate a role of prolactin in disease progression in multiple myeloma.
11700389 Vascular endothelial growth factor signaling pathway as an emerging target in hematologic 2001 Angiogenesis is important in a variety of physiologic and pathologic disorders. It is a central element in embryogenesis, ovulation, wound healing, diabetic retinopathy, and rheumatoid arthritis and in the establishment and spread of malignant tumors. Angiogenic factors include direct angiogens, indirect angiogens, and integrins. Direct angiogens stimulate the formation of new blood vessels directly. Indirect angiogens promote neovascular formation by paracrine stimulation of direct angiogens. Integrins mediate interactions between the developing vessels and components of the extracellular matrix. Vascular endothelial growth factor (VEGF) is a principal direct angiogen. By binding to 1 of 3 receptors (VEGFR-1, -2, or -3), it influences vasculogenesis during embryogenesis, physiologic and neoplastic angiogenesis, and lymphangiogenesis. Although the importance of angiogenesis in solid tumors has been recognized for some time, its exact significance in hematologic malignancies is less clear. Evidence now suggests that VEGF has a major role in the development and progression of hematologic malignancies such as acute leukemia, chronic leukemia, myelodysplasia, non-Hodgkin's lymphoma, and multiple myeloma. Potential therapeutic interventions to interrupt the VEGF signaling pathway of malignancy include antibodies that neutralize the growth factor and small molecules that inhibit the receptor tyrosine kinase activity of VEGF receptors.
11679750 Crystallization and preliminary X-ray crystallographic studies on a Fab fragment of the mo 2001 Nov The Fas-Fas ligand system is involved in apoptosis. The mouse anti-human Fas monoclonal antibody HFE7A (m-HFE7A) has a potential use in human therapy against autoimmune diseases such as rheumatoid arthritis. Information on the three-dimensional structure is essential for antibody humanization. Crystals of an antigen-binding fragment (Fab) of m-HFE7A were obtained by the hanging-drop vapour-diffusion method using sodium citrate as a precipitant and 2-methyl-2,4-pentanediol as an additive. Fast optimization to produce single crystals suitable for X-ray analysis was achieved by the streak-seeding technique. The crystals belong to the orthorhombic space group P2(1)2(1)2(1), with unit-cell parameters a = 43.4, b = 74.0, c = 133.8 A. The crystals diffract at least to 2.5 A resolution.
11677085 Insights into autoimmunity gained from structural analysis of MHC-peptide complexes. 2001 Dec The structural and functional properties of HLA-DQ and -DR molecules that confer susceptibility to several common autoimmune diseases, such as type 1 diabetes, rheumatoid arthritis and multiple sclerosis, have been defined. The relevant polymorphisms directly affect interaction with peptides, which provides strong support for the hypothesis that these diseases are peptide-antigen driven. Several studies indicate that structural modifications of peptides can affect MHC class II binding and/or TCR recognition and should be considered in the analysis of T cell responses in autoimmune diseases.
11571878 [Polymyalgia rheumatica in general practice]. 2001 Aug 20 BACKGROUND: Polymyalgia rheumatica is often diagnosed and treated in general practice. Rheumatologists have expressed concern about overdiagnosing and steroid treatment that conceals other diseases and deteriorating osteoporosis. MATERIAL AND METHODS: A ten-year material (1985-94) of polymyalgia rheumatica from a Norwegian general practice. RESULTS: Six out of 54 patients with the diagnosis polymyalgia rheumatica had their diagnose changed after one year. Average prednisolone starting dose was 31 mg, median treatment time for women was 20 months and for men 29 months. 10% were treated more than ten years, and 20% relapsed. Patients with fractures in the follow-up period had longer treatment periods; this indicates that a shorter treatment time may be important in preventing osteoporosis. INTERPRETATION: Diagnosing polymyalgia rheumatica can be done in general practice if there is good communication with second-line medical-services in cases with indistinct or serious symptoms. It is important to have in mind temporal arteritis, rheumatoid arthritis and malignancies. Treatment and follow-up of these patients is a task that needs stable and continuous relations between patient and doctor with special focus on the osteoporosis problem.
11484093 The role of Gd-enhanced three-dimensional MRI fast low-angle shot (FLASH) in the evaluatio 2001 In the field of lumbar spine disorders, three-dimensional (3-D) magnetic resonance imaging (MRI) can clearly depict a lumbar nerve root from the distal region to the dorsal root ganglion. In this study, we used a gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) enhanced-three-dimensional (3-D) fast low-angle shot (FLASH) sequence when examining lumbosacral disorders. The subjects were 33 patients (14 men and 19 women) in whom lumbosacral neural compression had been diagnosed clinically. Twenty-one patients had lumbar disc herniation, 11 had lumbar spinal stenosis, and 1 had lumbar radiculopathy caused by rheumatoid arthritis. Five subjects with low back pain were also studied as a control group. In all patients and in all 5 of the controls, the dorsal root ganglion of every root was enhanced clearly. There was no root enhancement in the 5 controls. Enhancement of the symptomatic nerve roots, caused by compression, was found in 11 of the 33 patients. All 11 patients had radiculopathy, and muscle weakness was more frequent in patients with enhanced nerve roots than in those without enhancement. There was no enhancement of the cauda equina, even in the patients with cauda syndrome. The enhancement effect may reflect some pathological condition of the compressed nerve root and needs to be studied further.
11453813 Improvement of Pyoderma gangrenosum and psoriasis associated with Crohn disease with anti- 2001 Jul BACKGROUND: Infliximab is an anti-tumor necrosis factor alpha monoclonal antibody IgG effective in the treatment and maintenance of remission of active refractory Crohn disease and associated draining enterocutaneous fistulae. Multiple infusions of infliximab show promising results in patients with rheumatoid arthritis. Currently, there is limited clinical experience with infliximab, and no published reports exist on its use in cutaneous disorders. OBSERVATIONS: We describe 2 patients with Crohn disease and pyoderma gangrenosum and 1 patient with Crohn disease and psoriasis who were treated with infliximab for recalcitrant Crohn fistulae, with concurrent improvement in their skin diseases. CONCLUSIONS: These cases suggest that infliximab, a promising therapeutic agent for refractory Crohn disease and fistulae, may also be effective in the treatment of pyoderma gangrenosum and psoriasis associated with Crohn disease.
11349215 The role of matrix metalloproteinases in tumor angiogenesis and tumor metastasis. 2001 Although a considerable amount of effort has been placed on discovering the etiologies of cancer, the majority of the basic cancer research existing today has focused on understanding the molecular mechanism of tumor formation and metastasis. Metastatic spread of tumors continues to be a major obstacle to successful treatment of malignant tumors. Approximately 30% of those patients diagnosed with a solid tumor have a clinically detectable metastasis and for the remaining 70%, metastases are continually being formed throughout the life of the tumor. Even after the tumor is excised, the threat of death is attributable to the metastasis that may occur through the remaining tumor cells. In addition, treating the metastasis often proves futile since metastasis often vary in size, composition, and anatomical location. New treatments blocking the formation of metastasis will provide greater chances of survival for cancer patients. One family of enzymes that has been shown over the years to play a role in tumor progression is the matrix metalloproteinase (MMP) family. The main function of MMPs, also known as matrixins, is degradation of the extracellular matrix physiologic function involving MMPs include wound healing, bone resorption and mammary involution. MMPs, however, also contribute to pathological conditions including rheumatoid arthritis, coronary artery disease, and cancer. Tumor cells are believed to utilize the matrix degrading capability of these enzymes to spread to distant sites. In addition, MMPs also are thought to promote the growth of these tumor cells once they have metastasized. This review will discuss the role of MMPs and their inhibitors in tumor invasion, angiogenesis and metastasis with special emphasis on the gelatinases, MMP-2 and MMP-9.
11276797 Epidemiology and pharmacoeconomic implications of non-steroidal anti-inflammatory drug-ass 2000 Dec Non-steroidal anti-inflammatory drugs (NSAIDs) are widely prescribed and used, especially to treat patients with osteoarthritis and rheumatoid arthritis. Since their introduction as a therapeutic class, a large body of literature has accumulated on the side-effects of these drugs. NSAIDs, through their inhibition of prostaglandin synthesis, can affect the renal and cardiovascular systems. However, the majority of reported side-effects are related to the gastrointestinal (GI) system, and the occurrence of these GI events adds significantly to the disease burden. Several factors have been identified that contribute to the risk of an NSAID-associated GI event. However, when considering risk, especially in clinical trials or observational studies, it is necessary to distinguish between baseline risk and NSAID-attributable risk, since this distinction can affect the results and conclusions of the study; NSAID-attributable risk is present in subjects who have few or no risk factors for upper GI toxicity. Safer NSAIDs, such as the new specific cyclooxygenase-2 inhibitors, when targeted to the appropriate patient (i.e. those with NSAID-attributable risk), should lead to improved outcomes and reduced costs.
11037631 [Biochemical markers of bone turnover and YKL 40 in ankylosing spondylitis. Relation to di 2000 Mar BACKGROUND: YKL-40 is a glycoprotein produced by chondrocytes and synovial cells. The plasmatic levels of this metabolite increase in some pathologies such as rheumatoid arthritis and osteoarthrosis, so much so that it can be considered an effective marker of disease activity and in the therapeutic monitoring of these diseases. It has been interesting to dose a group of both male and female subjects affected by seronegative spondylarthritis, comparing this parameter with the disease activity indexes and with the bone turnover markers. METHODS: The study has been carried out on 48 subjects (26 males and 22 females) between 17 and 68 years affected by spondylarthritis, diagnosed in conformity with ARA standards. None of the patients carried out basic treatment or by glycocorticoids, and 22 patients took FANS when required. In these subjects the disease activity markers (VES, PCR, fibrinogen, mucoprotein) and some of the classic bone remodelling markers (blood calcium and phosphates, calciuria, phosphaturia, Ca++, Ntx, osteocalcine, bone isoenzyme of alkaline phosphatase, hydroxyproline, procollagen and YKL-40) were dosed. RESULTS: The comparison between different parameters pointed out that the highest values are obtained in subjects of most advanced age with the highest phlogosis indexes, without any correlation with sex. The quite interesting comparison shows a correlation between the bone remodelling indexes and YKL-40, being particularly remarkable when the disease is more aggressive or during relapse. CONCLUSIONS: It is then possible to confirm that, though preliminary, these data may suggest evaluations on wider case histories to research YKL-40 as a surgical monitoring marker in seronegative poliarthritis.
11029331 An investigation into causative factors in patients with bronchiectasis. 2000 Oct Bronchiectasis is a pathologic description of lung damage characterized by inflamed and dilated thick-walled bronchi. These findings may result from a number of possible causes and these may influence treatment and prognosis. The aim of this study was to determine causative factors in 150 adults with bronchiectasis (56 male, 94 female) identified using high-resolution computerized tomography. Relevant factors were identified in the clinical history; cystic fibrosis gene mutation analysis was performed; humoral immune defects were determined by measuring immunoglobulins, IgG subclasses and functional response to Pneumovax II vaccine; assessment was made of neutrophil function (respiratory burst, adhesion molecule expression, and chemotaxis); ciliary function was observed and those likely to have allergic bronchopulmonary aspergillosis (ABPA) were identified. Causes identified were: immune defects (12 cases), cystic fibrosis (4), Young's syndrome (5), ciliary dysfunction (3), aspiration (6), panbronchiolitis (1), congenital defect (1), ABPA (11), rheumatoid arthritis (4), and early childhood pneumonia, pertussis, or measles (44). Intensive investigation of this population of patients with bronchiectasis led to identification of one or more causative factor in 47% of cases. In 22 patients (15%), the cause identified had implications for prognosis and treatment.
11012663 Thioredoxin reductase as a pathophysiological factor and drug target. 2000 Oct Human cytosolic thioredoxin reductase (TrxR), a homodimeric protein containing 1 selenocysteine and 1 FAD per subunit of 55 kDa, catalyses the NADPH-dependent reduction of thioredoxin disulfide and of numerous other oxidized cell constituents. As a general reducing enzyme with little substrate specificity, it also contributes to redox homeostasis and is involved in prevention, intervention and repair of damage caused by H2O2-based oxidative stress. Being a selenite-reducing enzyme as well as a selenol-containing enzyme, human TrxR plays a central role in selenium (patho)physiology. Both dietary selenium deficiency and selenium oversupplementation, a lifestyle phenomenon of our time, appear to interfere with the activity of TrxR. Selenocysteine 496 of human TrxR is a major target of the anti-rheumatic gold-containing drug auranofin, the formal Ki for the stoichiometric inhibition being 4 nM. The hypothesis that TrxR and extracellular thioredoxin play a pathophysiologic role in chronic diseases such as rheumatoid arthritis, Sjögren's syndrom, AIDS, and certain malignancies, is substantiated by biochemical, virological, and clinical evidence. Reduced thioredoxin acts as an autocrine growth factor in various tumour diseases, as a chemoattractant, and it synergises with interleukins 1 and 2. The effects of anti-tumour drugs such as carmustine and cisplatin can be explained in part by the inhibition of TrxR. Consistently, high levels of the enzyme can support drug resistance. TrxRs from different organisms such as Escherichia coli, Mycobacterium leprae, Plasmodium falciparum, Drosophila melanogaster, and man show a surprising diversity in their chemical mechanism of thioredoxin reduction. This is the basis for attempts to develop specific TrxR inhibitors as drugs against bacterial infections like leprosy and parasitic diseases like amebiasis and malaria.
10976121 Arthroscopy for failed shoulder arthroplasty. 2000 Sep PURPOSE: It was the purpose of this study to describe the specifics of technique and results of arthroscopic evaluation and treatment of failed shoulder arthroplasties in 10 patients with early and late complications of shoulder arthroplasty. TYPE OF STUDY: Case series. MATERIALS AND METHODS: Ten patients (2 bilateral) underwent 13 arthroscopies after poor results following shoulder arthroplasty. The arthroscopic diagnoses ranged from rotator cuff tears in 5 shoulders, fibrosis and scarring of the long head of the biceps in 5 shoulders, impingement and biceps tendinitis in 1 shoulder, and capsular contracture in 1 shoulder. We performed 4 mini-open rotator cuff repairs, 1 open rotator cuff repair with revision of the humeral component, 5 arthroscopic debridements of the long head of the biceps, 2 arthroscopic decompressions with biceps tenodesis, and 1 arthroscopic capsular release. RESULTS: Before arthroscopy, the preoperative Hospital for Special Surgery (HSS) scores were 6 fair and 6 poor. At latest follow-up, there were 3 excellent, 4 good, and 5 fair results. There was a statistically significant improvement in HSS scores and range of motion for all patients in this study. All patients were satisfied with the results of the procedure. There were no infections or wound problems and neurovascular status was unaltered after arthroscopy. There was 1 intraoperative complication, a periprosthetic humerus fracture after manipulation in an osteoporotic woman with rheumatoid arthritis. CONCLUSION: Arthroscopy proved to be a reliable diagnostic and therapeutic tool in dealing with some of the postoperative complications encountered both early and late after shoulder arthroplasty. Careful attention to surgical technique, including use of blunt trocars, traction, and intraoperative prophylactic antibiotics, can minimize complications of arthroscopy in this setting.
10963170 The Roper-Tuke total elbow arthroplasty. 4- to 10-year results of an unconstrained prosthe 2000 Jul We report the results of a series of 59 unconstrained total arthroplasties of the elbow after a mean follow-up of 6.5 years (4 to 10). All the patients had rheumatoid arthritis. The indication for surgery was pain in all but one. Outcome was assessed by the Mayo Elbow Performance Index (MEPI). Of the 59 arthroplasties, two were lost to follow-up. Ten patients died, but as two of their arthroplasties were failures we included them in the results. The outcome in the remaining 49 was excellent in 26 (53%), good in 15 (31%), fair in one (2%) and poor or a failure in seven (14%). There was an improvement in the pain score (p < 0.001), movement (p < 0.001) and function (p < 0.001). Two patients developed instability, but neither required further surgery. There was a mean increase of 21 degrees in flexion and of 7 degrees in extension. The overall rate of complications was 33.9%. Lesions of the ulnar nerve, one of which did not recover, occurred in four patients, deep infection in two and stiffness in five. The rates of complications were similar to those in recent reports of other elbow arthroplasties. We carried out a radiological analysis of 39 arthroplasties which showed radiolucent lines around the humeral component in 22 and the ulnar component in 15. There were lower scores on the MEPI for those with radiolucent lines around the humeral component.
10943216 [Late spreading of tuberculosis in tubercular spondylitis]. 2000 Jul 14 HISTORY AND ADMISSION DIAGNOSIS: A 65-year-old man, known to have had a gastric ulcer and chronic rheumatoid arthritis as well as alcohol and nicotine abuse, was admitted because of suspected endocarditis. Physical examination revealed marked pain on pressure over the throacic spine. Vesicular breath sounds were reduced over the entire thorax and there was a systolic murmur over Erb's point (above the right clavicle). There was a purulent bursitis over the olecranon. INVESTIGATIONS: Abnormal laboratory tests were: elevated C-reactive protein, elevated leucocyte count (up to 33 thousand during the hospital stay). Smears from the bursitis and blood cultures revealed Staph. aureus. Computed tomography demonstrated a fracture of the 7th thoracic vertebra with a paravertebral abscess. Echocardiography showed anatherosclerotic aortic valve with floating particles. DIAGNOSIS, TREATMENT AND COURSE: Treatment of the suspected staphylococcal bacteraemia with purulent bursitis, spondylitis and aortic valvar endocarditis was begun with broad-spectrum antibiotics, but the patient soon developed a severe acute respiratory distress syndrome and he died of multi-organ failure. Autopsy revealed as cause of death left heart failure with aortic valvar endocarditis and gelatinour pneumonia caused by late tubercular dissemination from the tubercular spondylitis. CONCLUSION: Tuberculosis can be a life-threatening infection. Uncharacteristic history and extrapulmonary manifestations can make it very difficult to arrive at the correct diagnosis.
10885082 Supporting practice-based audit: a price to be paid for collecting data. 1999 Oct BACKGROUND: There has been considerable investment by health authorities in the funding of support staff whose job is to collect data for audit purposes. It is important to understand what costs are involved in such a data collection exercise. The cost advantages of using existing practice staff or externally funded staff are not known. AIM: To assess the cost of transposing data on workload to computer software for audit purposes and retrieving data on five chronic diseases from case records. METHOD: Four audit support staff monitored the time taken to collect specific data as part of a broad audit programme in 12 training practices within one health board area in the West of Scotland in 1997. The time taken was used to estimate comparative costs for using a receptionist or practice nurse for carrying out a similar exercise. RESULTS: Average costs for collecting data per 1000 patients for waiting time, appointments, recall, and telephone audits were 5.24 Pounds for reception staff, 5.64 Pounds for audit support staff, and 9.68 Pounds for a practice nurse. The average cost for collecting data per patient with diabetes, asthma, epilepsy, hypertension, or rheumatoid arthritis was 1.48 Pounds for reception staff, 1.60 Pounds for audit support staff, and 2.74 Pounds for a practice nurse. CONCLUSIONS: The cost of collecting data varies considerably depending on which staff are chosen for the purpose. Practices should consider carefully how best to collect data for audit in terms of cost.
10830859 Design of copper-based anti-inflammatory drugs. 2000 Apr It has been shown that the inflammation associated with rheumatoid arthritis can be reduced using copper complexes. In order to improve the bioavailability of copper and hence efficacy of these complexes we have synthesized three different series of ligands, each having different characteristics. Thermodynamic results for copper(II) complexes for these polyamino, diaminodiamido and triaminodiamido ligands are presented. The polyamino ligands form the most stable complexes in vivo but tissue distribution studies in mice show that [Cu(3,6,9,12-tetraazatetradecanedioate)] is excreted rapidly, unchanged in the urine. The diamino ligand complexes are much less stable than their polyamino analogues and animal studies using [Cu(N,N'-bis[2-(dimethylamino)ethyl]-ethanediamide)H2] indicate that the complex dissociates in vivo and is excreted slowly via the liver. The triaminodiamido copper(II) complexes are approximately 2 log units more stable than their diamino analogues. Computer simulation calculations indicate that these complexes are also likely to dissociate in plasma. Measured partition coefficients, however, suggest the possibility of dermal absorption.