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ID PMID Title PublicationDate abstract
16092658 An audit of serological tests carried out at clinical laboratory of Ayub Teaching Hospital 2005 Apr BACKGROUND: Clinical audit is an important tool for reviewing and improving the quality of service in clinical laboratories. Here we present an audit of total serology test requests and the frequency of positive tests out of these in a calendar year. METHODS: This is an audit of serology tests carried out at Microbiology section of Clinical Laboratory of Ayub Teaching Hospital, Abbottabad. We counted all the serology test requests for the year 2004. These tests requests were grouped month wise. The frequency of positive tests out of the total test requests were calculated. The tests included Widal, Toxoplasma, Brucella, Anti DNA, Anti Nuclear factor (ANF), Rheumatoid Arthritis Factor (RAF), HIV, HBsAg, HCV, Intra Chromatographic Technique for tuberculosis (ICT-TB), Purified Protein Derivative (PPD), Venereal Disease Research Laboratory (VDRL) test, Anti-Streptolysin-O-test (ASOT) and pregnancy test. RESULTS AND CONCLUSIONS: This audit gives a clear idea of trends of test requests in our hospital. It reflects accuracy of clinicians' judgment in some tests and failure in others, prevalence of different diseases, seasonal variation in number of test requests for some tests and impact of awareness campaigns on attitude of clinicians towards certain diseases. This will help us in planning our laboratory requirements to improve quality.
16022573 Nitric oxide donor drugs: an update on pathophysiology and therapeutic potential. 2005 Jul The discovery of the multiple physiological and pathophysiological processes in which nitric oxide (NO) is involved has promoted a great number of pharmacological researches to develop new drugs that are capable of influencing NO production directly and/or indirectly for therapeutic purposes (i.e, NO-releasing drugs, NO-inhibiting drugs, and phosphodiesterase V inhibitors). In particular, the so-called NO donor drugs could actually have an important therapeutic effect in the treatment of many diseases such as arteriopathies (atherosclerosis and its sequelae, arterial hypertension and some forms of male sexual impotence), various acute and chronic inflammatory conditions (colitis, rheumatoid arthritis and tissue remodelling), and several degenerative diseases (Alzheimer's disease and cancer). The old organic nitrates show some well-known pitfalls including the induction of tolerance and acute side effects related to abrupt vasodilation such as cephalea and hypotension, which limit their therapeutic indications. A low therapeutic index (i.e., peroxynitrite toxicity) has always characterised the sydnonimines class. A series of interesting new classes of NO donors are under intense pharmacological investigation and scrutiny (S-nitrosothiols, diazeniumdiolates and NO hybrid drugs), each characterised by a particular pharmacokinetic and pharmacodynamic profile. The most important obstacle in the field of NO donor drugs is represented by the difficulty in targeting NO release, and thereby its effects, to a particular tissue.
16009053 Physical activity for secondary prevention of disease. Systematic reviews of randomised cl 2005 May BACKGROUND: Physical activity is recommended for secondary prevention of several diseases but it is not always clear how reliable the evidence is. METHODS: We searched MEDLINE and The Cochrane Library for systematic reviews of randomised clinical trials published 1998-2004. RESULTS: We identified 30 eligible systematic reviews and excluded 13 that contained trials covered in larger reviews or were older than other reviews on the same subject. Physical activity decreased all-cause mortality in patients with coronary heart disease, odds ratio 0.73 (95% confidence interval 0.54 to 0.98), increased maximum walking time in patients with intermittent claudication by 6.5 min (4.4 to 8.7), and decreased pain in patients with osteoarthritis of the knee, standardised mean difference 0.34 (0.24 to 0.44). There were positive effects also in heart failure, chronic obstructive lung disease, type 2 diabetes and fibromyalgia, but they need confirmation in high-quality trials. Exercise improved quality of life in several conditions and generally led to improved physical performance. An effect was not shown in stroke, asthma, rheumatoid arthritis, acute or chronic low back pain, chronic fatigue syndrome, depression, cystic fibrosis or HIV/AIDS. The occurrence of harms was generally not reported. CONCLUSION: Physical activity can have important, and even life-saving, effects as secondary prevention of disease, but more and better trials are needed to fully assess its benefits and harms, in particular trials that compare exercise with drugs.
15961271 Cognitive impairment in three subtypes of multiple sclerosis. 2005 Dec Patients with relapsing, primary progressive, and secondary progressive MS were administered the Tower of London and the Stroop Color-Word Interference Test, yielding several measures of executive function and speeded information processing. MS patients' performance was compared with healthy controls and with a clinical control group consisting of patients with rheumatoid arthritis. The MS patients performed the tests more slowly, but did not differ from either group of controls on measures of executive function. Slowing in the speed of information processing was characteristic of MS patients across two basic tasks differing in terms of controlled versus automatic processing and in terms of whether or not rapid responding was an explicit feature of successful performance. Although evident in all subtypes, this slowing was more pronounced in secondary progressive patients and somewhat less pronounced in primary progressive patients. Furthermore, the slowing was unrelated to patients' disability status or level of depression.
15958063 Haematopoietic stem cell transplantation in the treatment of severe autoimmune disease: re 2005 Jul Around 700 patients have received an autologous haematopoietic stem cell transplant (HSCT) as treatment for a severe autoimmune disease (AD). The majority of these have been within the context of phase I/II clinical trials and following international guidelines proposed 7 years ago. In general, a positive benefit/risk ratio has led to phase III prospective randomized controlled trials in multiple sclerosis (MS), systemic sclerosis (SSc) and rheumatoid arthritis (RA) in Europe. In the US, similar trials are being planned for SSc, MS and systemic lupus erythematosus (SLE). Transplant related mortality (TRM) has fallen in all disease subgroups since the inception due to more appropriate patient selection, and so far a clear advantage of the more intense myeloablative regimens in terms of remission induction and relapse rate has not emerged. Although each AD has a different profile, over a third of patients have sustained a durable remission, often with no further need for immunosuppressive drugs. In those who relapsed, many responded to agents which pre transplant had been ineffective. The study of immune reconstitution and gene expression pre and post HSCT is being undertaken to further understand the mechanism of autoimmunity.
15784801 Written emotional expression produces health benefits in fibromyalgia patients. 2005 Mar OBJECTIVE: Written expression of traumatic experiences, an intervention found to have health benefits in rheumatoid arthritis, asthma, and breast cancer, was tested in a randomized, controlled trial with female fibromyalgia patients. It was hypothesized that relative to controls, patients engaging in the writing intervention would experience improved status on psychological well-being and physical health variables. METHODS: Patients (N = 92) were randomized into a trauma writing group, a control writing group, or usual care control group. The two writing groups wrote in the laboratory for 20 minutes on 3 days at 1-week intervals. Psychological well-being, pain, and fatigue were the primary outcome variables. Assessments were made at pretreatment, posttreatment, 4-month follow-up, and 10-month follow-up. RESULTS: The trauma writing group experienced significant reductions in pain (effect size [ES] = 0.49) and fatigue (ES = 0.62) and better psychological well-being (ES = 0.47) at the 4-month follow-up relative to the control groups. Benefits were not maintained at the 10-month follow-up. CONCLUSION: Fibromyalgia patients experienced short-term benefits in psychological and health variables through emotional expression of personal traumatic experiences.
15692824 Atlantoaxial osteoarthritis: case series and review of the literature. 2005 Jun The intention of this study is to present our experience in the surgical treatment of painful atlantoaxial osteoarthritis (AAOA) and review the literature on this subject. Osteoarthritis of the atlantoaxial joints is more common than is generally suspected. It has a prevalence between 5 and 18%. Only a minority of patients becomes symptomatic suffering from severe suboccipital pain, irradiating into the occiput, vertex and sometimes as far as the eyes. Most often, these patients can successfully be treated conservatively. Some of these patients however require operative treatment. The study includes five patients with painful AAOA (one posttraumatic, four idiopathic) not responding to conservative treatment for a minimum of six months. Rheumatoid arthritis was excluded. All but one patient were female and all but one patient were over 50 years old (mean 64 years). The origin of pain was confirmed by diagnostic C1-C2 facet blocks in all patients. The patients were treated with a C1-C2 transarticular screw fixation and Gallie type fusion. Patients were followed clinically and radiologically for a minimum of 24 months. Mean follow-up was 38 months (24-48). In all patients the typical pain disappeared immediately after surgery and has not reoccurred. Pain intensity on the VAS decreased from 100 to 34. At the latest follow-up radiologically solid fusion and stable implants were found in all cases. All five patients would undergo this surgery for the same condition again. C1-C2 fusion effectively relieves occipitocervical pain in AAOA non responsive to conservative treatment.
17090024 Activity-based protein profiling reagents for protein arginine deiminase 4 (PAD4): synthes 2006 Nov 15 Protein arginine deiminase 4 (PAD4), which catalyzes the post-translational conversion of peptidyl arginine to peptidyl citrulline, is widely regarded as one of the best new targets for the development of a novel rheumatoid arthritis therapeutic. In addition to its presumed role in this disease, PAD4 is also a calcium-dependent histone deiminase that acts as a transcriptional co-repressor. Herein we describe the design, synthesis, and in vitro evaluation of two fluorescently labeled activity-based protein profiling (ABPP) reagents that specifically and irreversibly modify the active, that is, calcium-bound, form PAD4 with equal affinity to previously described small molecule chemical probes of PAD4 function. These fluorescently tagged ABPPs will be useful for identifying the conditions under which this enzyme is activated in vivo and may prove to be useful RA diagnostics.
17062028 Treatment of inflammatory dermatoses by tumour necrosis factor antagonists. 2006 Nov BACKGROUND: The treatment of inflammatory skin diseases is at present often empirical as causal therapeutic approaches, based on an incomplete knowledge of the immune pathogenesis, are mostly unavailable. The currently applied treatments can in fact lead to remission of the disease; however, under certain circumstances undesirable side-effects must be expected. On the basis of experience gained in cytokine modulation therapy of chronic inflammatory diseases such as rheumatoid arthritis and psoriasis, the application of TNF-alpha inhibitors represents a novel, more specific, and effective therapeutic option for distinct chronic inflammatory diseases. PATIENTS AND METHODS: The current status of the therapeutic effect of TNF-alpha blockers is discussed based on our own observations and a review of the current literature. Also discussed are potential undesirable side-effects and possible contraindications of this therapy. RESULTS AND CONCLUSIONS: Based on recent findings, the use of TNF-alpha blockers seems to be promising in the treatment of therapy-resistant inflammatory dermatoses. At present, guidelines for indications and contraindications of anti-TNF-alpha treatment of inflammatory skin disorders are rare. Such guidelines are necessary to improve the efficacy of anticytokine treatment and the reduction of side-effects.
17041995 Adherence with drug therapy in the rheumatic diseases Part one: a review of adherence rate 2005 Drug therapy plays a major role in the management of many rheumatic diseases and is particularly important in rheumatoid arthritis (RA) because of the significant rates of morbidity and mortality (Pincus, 1995). Understanding of the pathogenesis of RA has led to the development of new and more effective drugs (Emery et al., 1999), but the ultimate efficacy of any drug therapy depends upon the patient's decision to take it. There is widespread agreement that many people with rheumatic disease do not adhere to their medication regimens (Deyo et al., 1981; Belcon et al., 1984; Pullar et al., 1988; Hill et al., 2001). Research has demonstrated that 50% of women taking hormone replacement therapy for the prevention of osteoporosis discontinue treatment after a year (Fordham, 2000) and similar rates of discontinuation are found in other chronic diseases (Haynes et al., 1996, 2000). This is bewildering as, in asymptomatic illnesses such as hypertension and diabetes, the expectation is that levels of adherence would be lower than in diseases where pain and stiffness are present. The picture becomes even more confusing when we consider the findings from a recent multi-country study of RA, which found no association between adherence and disease severity, nor with the treatment prescribed (Viller et al., 1999). In chronic disease poor adherence is commonplace. The World Health Organization (WHO) recognizes this and has recently stated that 'poor adherence to treatment of chronic diseases is a worldwide problem of striking magnitude' and cites adherence to long-term therapy for chronic illnesses in developed countries averaging just 50% (WHO, 2003). The first part of this two part review focuses on adherence with drug therapy, and the second part discusses different methods of measuring it.
16970913 Antioxidant properties of bucillamine: possible mode of action. 2006 Oct 27 The antioxidant properties of Bucillamine (BUC), a di-thiol compound used for treatment of rheumatoid arthritis (RA) and its possible mode of action, were investigated. BUC exhibits potent antioxidant activity similar to those of trolox and ascorbic acid. It reduces the stable free radical diphenyl-2-picrylhydrazyl (DPPH) with IC(50) of 18.5+/-0.1 micromol, its relative antioxidant activity by the ferric reducing ability (FRAP) is 2.07+/-0.01 mM and by the trolox equivalent antioxidant capacity (TEAC), 1.46+/-0.05 mM. However, its superoxide and apparent hydroxyl radical scavenging activities are low (IC(50) at millimolar concentrations). We found that BUC is a strong iron (II) and copper (II) chelator. This finding is very important since these metal ions are significantly higher in RA patients and may be involved in oxidative stress-induced damage. Our study suggests that BUC is a potent antioxidant which exerts its beneficial therapeutic activities in RA patients by metal chelation rather than by scavenging free radical species.
16938258 [Vascular development in inflammatory bowel disease]. 2006 Aug There are 4 major concepts in vascular development: vasculogenesis (formation of blood vessels from angioblasts), angiogenesis (formation of vascular sprouts from preexisting vessels), arteriogenesis (thickening and development of vessels) and lymphangiogenesis (formation of lymphatic vessels). In the last decade, these concepts, especially angiogenesis and lymphangiogenesis, have acquired major importance due to their role in tumoral growth and metastatic dissemination. Moreover, the activity of various diseases that involve chronic inflammation, such as asthma, psoriasis and rheumatoid arthritis, has been associated with vascular development. Several growth factors and cytokines are involved in this process and consequently investigation into these elements, both in peripheral blood and their expression in affected tissues, could elucidate the role of vascular development in diseases whose pathogenesis involves chronic inflammation, such as inflammatory bowel disease. The presence of distinct molecules involved in vascular development processes, such as vascular endothelial growth factor (VEGF), basic fibroblastic growth factor and placental growth factor, among others, has been studied in both ulcerative colitis and Crohn's disease, although not extensively. It has been suggested that the phenomena of vasculogenesis, angiogenesis and lymphangiogenesis play a critical, although not exclusive, role in the inflammation that characterizes inflammatory bowel disease. In general, the results obtained to date suggest that new vascular formation is involved in the pathogenesis of these diseases.
16918457 The cannabinergic system as a target for anti-inflammatory therapies. 2006 Habitual cannabis use has been shown to affect the human immune system, and recent advances in endocannabinoid research provide a basis for understanding these immunomodulatory effects. Cell-based experiments or in vivo animal testing suggest that regulation of the endocannabinoid circuitry can impact almost every major function associated with the immune system. These studies were assisted by the development of numerous novel molecules that exert their biological effects through the endocannabinoid system. Several of these compounds were tested for their effects on immune function, and the results suggest therapeutic opportunities for a variety of inflammatory diseases such as multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease, atherosclerosis, allergic asthma, and autoimmune diabetes through modulation of the endocannabinoid system.
16906083 Intraoperative contamination influences wound discharge and periprosthetic infection. 2006 Nov Intraoperative bacterial contamination increases risk for postoperative wound-healing problems and periprosthetic infection, but to what extent remains unclear. We asked whether bacterial contamination of the instruments and bone during primary prosthesis insertion was associated with prolonged wound discharge and subsequent periprosthetic infection. During 100 total hip arthroplasties, four intraoperative cultures were taken from the instruments and two portions of removed bone. Postoperatively, the duration of wound discharge was monitored, with Day 5 as the cut-off point. All patients were followed for 2 years to determine whether periprosthetic infection occurred. Bacterial contamination occurred in 36 operative procedures (36%). We found an association between intraoperative contamination and prolonged wound discharge, with a relative risk of 2.5. The culturing of removed bone had a positive predictive value of 81% to 90%. Other factors associated with prolonged wound discharge were rheumatoid arthritis (relative risk, 6.4), use of cement (relative risk, 1.6), and increased blood loss (relative risk, 1.5).
16713722 MRI and non-cartilaginous structures in knee osteoarthritis. 2006 Magnetic resonance imaging (MRI) provides a sensitive tool for examining all the structures involved in the osteoarthritis (OA) process. While much of the MRI literature previously focussed on cartilage, there is increasing research on whole-organ evaluation and including features such as synovitis, bone marrow edema, and meniscal and ligamentous pathology. The aim of this session at the Outcome Measures in Rheumatology Clinical Trials (OMERACT)-Osteoarthritis Research Society International (OARSI) Workshop for Consensus in Osteoarthritis Imaging was to describe the current MRI methods for identifying and quantifying non-cartilaginous structures and review their associations with both OA symptoms and structural progression. Although there is much experience in measuring synovitis (derived from the rheumatoid arthritis literature), only one study has reported an association of MRI-detected synovitis and effusions with OA pain. Bone marrow edema lesions, which may represent areas of trabecular remodelling, have been associated with pain and compartment-specific structural deterioration. MRI studies have confirmed the frequency and importance of meniscal damage in progressive cartilage loss, but not related such damage to symptoms. Osteophytes have been associated with cartilage loss and malalignment to the side of the osteophyte. Ligament damage, including anterior cruciate ligament tears, has been found more commonly than expected in painful OA knees. Improvements in quantitative and semi-quantitative assessments of non-cartilage features will greatly assist understanding of the OA process and its response to therapy.
20477658 Is there an immunologic basis for schizophrenia? 2005 May The cause of schizophrenia remains an enigma despite the development of effective antipsychotic drugs that act by modulating the dopaminergic and serotonergic systems in the limbic region of the brain. Although such drugs are undoubtedly clinically effective, many patients do not fully benefit from such treatments, and the side effects, such as weight gain and the exacerbation of insulin-dependent diabetes mellitus, are often problematic. In recent years, the possible cause of schizophrenia has switched from an emphasis on neurotransmitter dysfunction to possible genetic and neurodevelopmental abnormalities. The close link between the loci for insulin-dependent diabetes mellitus, human lymphocyte antigen system and schizophrenia may indicate an immune component for this disorder. This hypothesis gains further credibility from epidemiologic studies showing a link between viral infections in utero and the subsequent development of schizophrenia; the negative correlation between rheumatoid arthritis and schizophrenia gives further support to the hypothesis. Thus, the immune hypothesis of schizophrenia has developed from an understanding of the genetic, environmental and infectious sequelae that underlie the immune changes involving the cellular and humoral components of the adaptive immune system. The changes in the types of T-lymphocytes that are involved in the adaptive immune response are of particular importance. The T-helper 1 cells, that secrete interleukin-2 and interferon-gamma for example, are reduced in activity while the T-helper 2 cells, together with the macrophages, show an increased secretion of interleukins-6 and -10. As these immune changes are normalized following effective antipsychotic drug treatment, new types of antipsychotics could be developed that act directly on the imbalance in the components of the adaptive immune system. The finding that some anti-inflammatory drugs can exhibit modest antipsychotic activity is further evidence of the validity of the autoimmune nature of schizophrenia and an indication that drug development based on this concept may be a fruitful area for future research.
16863659 Targeting BAFF: immunomodulation for autoimmune diseases and lymphomas. 2006 Dec In an effort to develop more effective treatments for inflammatory diseases, immunologists have targeted numerous molecular pathways, but with limited success. Notable exceptions are anti-TNF agents, which have proved efficacious in a proportion of rheumatoid arthritis (RA) patients. Another TNF family member, termed BAFF ("B cell-activating factor belonging to the TNF family"), plays a central role in autoimmune diseases, as well as in B cell maturation, survival, and T cell activation. Agents that block BAFF have proven to be highly effective in the treatment of certain autoimmune conditions in mice. In addition, phase II data in human clinical trials for RA appear very promising. BAFF is also a survival factor for certain B cell lymphomas. Despite the relatively recent identification of BAFF, this molecule has provided considerable new insight into B cell homeostasis and immune function, and represents an important new molecular target for treatment of autoimmune diseases and lymphomas.
16855172 Adipose tissue has anti-inflammatory properties: focus on IL-1 receptor antagonist (IL-1Ra 2006 Jun The formation of adipose tissue could result from abnormal metabolic processes and, at the local level, from chronic inflammatory processes such as those occurring in the synovial cavity in rheumatoid arthritis or osteoarthritis, or the peritoneal cavity in various inflammatory processes of the digestive system. Adipocytes are said to produce many hormones and proinflammatory mediators. So far, however, little attention has been paid to cytokine inhibitory molecules. Based on our observation of high levels of serum interleukin receptor antagonist (IL-1Ra) in obese patients contrasting with decreased levels after gastric bypass surgery, we found white adipose tissue (WAT) in the human system to be the main source of IL-1Ra. IL-10 was also present in WAT. Furthermore, we found that interferon-beta (IFN)-beta was the principal cytokine inducing IL-1Ra in various WAT, such as that present in the synovium. We suggest that in addition to other functions adipose tissue may give rise to a host-defense mechanism against local inflammation and that fibrotic tissue in the vicinity may further induce IL-1Ra in adipocytes via the production of IFN-beta.
16838644 [Prospects of treatment using interferon for bone diseases]. 2006 Jul Osteoblasts and osteoclasts produce a variety of cytokines to maintain bone homeostasis. One of the most important cytokines, receptor activator of nuclear factor-IkappaB ligand (RANKL), is essential for osteoclastogenesis. Recently, it was shown that activated T cells promote osteoclastogenesis through RANKL expression and also negatively affect osteoclastogenesis through interferon (IFN)-gamma production. Additionally, it was revealed that IFN-beta was involved in osteoclast regulation by signaling cross-talk with RANKL and that it contributed to the maintenance of normal bone mass. These studies indicate that there are complex regulatory interactions between bone-remodeling cells and immune cells, which depend on the balance between RANKL and IFN. Thus, the interaction between T cells and bone cells could be physiologically critical for the maintenance of normal bone metabolism, and IFN might be an attractive cytokine for use in therapy for bone disease in pathological bone resorptive conditions such as rheumatoid arthritis, osteoporosis, osteomyelitis and bone metastasis of cancers.
16827241 [Optimization of a method for determination of complement activity from 50% hemolysis of s 2006 May The method for determination of compliment activity from 50% hemolysis of sensitized blood cells (CH5) was modified in accordance with the recommendations of the International Clinical Chemistry Association, which could reduce the consumption of reagents, enhance the accuracy and reproducibility of results. The activity of CH50 was calculated for each serum sample by regression analysis, by graphically reflecting the results and by assessing the quality of each performance. The sigma-deviation method was used to calculate the normal CH50 ranges (55-160 conventional units) whose values were in compliance with the international standards. A series of experiments were made to assess the reproducibility of results. To evaluate the diagnostic informative value, the authors analyzed serum samples from 119 persons: 49 apparently healthy individuals, 74 patients with allergic diseases that are generally unattended by hypocomplementemia (Group 1) and 76 with disease the risk of which is increased in the presence of complement system defect (Group 2). Group 1 patients were those who had bronchial asthma or utricaria; Group 2 patients were those who had systemic lupus erythematosus, scleroderma, rheumatoid arthritis, chronic glomerulonephritis, acute glomerulonephritis, chronic furunculosis, chronic tonsillitis, or necrotic vasculitis. In Group 1, the value of CH50 was similar to that in the group of donors (108.0 +/- 3.1 and 105.1 +/- 3.8, respectively; p = 0.565), but it significantly differed from its mean value (91.6 +/- 5.1) in Group 2 (p = 0.00724). The difference in CH50 was also significant in the group of donors and Group 2 (p = 0.0349).