A well-functioning immune system is of paramount importance in preventing lymphomagenesis. Both immunostimulation, which causes excessive cell turnover and increased potential for mutations, and immunosuppression, causing a decreased ability to monitor and halt aberrant cell proliferation, have been implicated in cancer development. Autoimmune diseases are characterized by excessive activation of lymphocytes due to a dysregulated response to self-antigens. The treatments for autoimmune disease therefore share a common goal of immunosuppression. While treatments have become better-targeted to specific inflammatory pathways over the last 30 years as opposed to general immunosuppression, there remains a high risk of hematologic malignancy for patients with autoimmune disease relative to the general population. There are numerous types of autoimmune disease, as well as much heterogeneity within each diagnosis from patient to patient. The focus of this thesis is Rheumatoid Arthritis (RA), a strikingly common disease affecting 0.5-1.0% of the world population and characterized by debilitating, painful, joint-deforming symptoms and difficulty in achieving remission. [1] Therapeutic intervention often necessitates a trial and error approach and various combinations of drugs, in the same way cocktails of chemotherapeutic drugs are tailored to treat cancers due to their heterogeneity. Drugs for the treatment of autoimmune diseases are collectively known as Disease-Modifying Anti-Rheumatic Drugs (DMARDs) and were only first widely used for the treatment of RA in the 1980s. This short history of widespread use, along with the great variability in manifestation of disease and treatment course, has historically limited the ability of observational studies to determine the safety of DMARDs in terms of malignancy risk. Only in the past few years has enough information been available, drawn mostly from national healthcare databases in several countries, to enable strong conclusions about the effects of DMARDs on malignancy risk. This thesis aims to provide a comprehensive review of the most recent and well-designed studies regarding currently available DMARDs for RA and their effects on the risk of lymphoma.

No description available.

M.Tech.: Chiropractic, Durban Institute of Technology, 2006. / The purpose of this pragmatic controlled clinical trial was to investigate the efficacy of low-level laser therapy (LLL T) as a part of the palliative management of the hand symptoms of rheumatoid arthritis (RA). The results were based upon subjective and objective clinical findings. LLLT may offer a viable treatment option for the hand symptoms of RA as its application theoretically supports and suggests that the physiological effects of LLL Tare biostimulation, improved metabolism, increased cell metabolism, improved blood circulation, vasodilatation, analgesic effects, anti-inflammatory and anti-edematous effects; all of which are desired in the treatment of RA (Baxter, 1994; Kahn, 1994, Liggins, 2002). There is however controversy within the literature as to the efficacy of LLLT (Asada et al., 1991; Bliddal et al., 1987; Goats. et al., 1996; Hall et al., 1994; Heussier et al., 1993; Johannsen et al., 1994; Palmagren et al., 1989; Walker et aI., 1987). This is partially attributable to the lack of consensus regarding the methodology applied in these studies. Other inconsistencies regarding the efficacy of laser in the treatment of RA exist due to the wide range of differing wavelengths and doses that have been used in the published reports, thereby making it difficult to effectively compare studies (Asada et al., 1991; Goats et al., 1996; Hall et ai., 1994; Haslett et al., 2001, Heussier et ai., 1993; Johannsen et al., 1994; Palmagren et al., 1989; Walker et al., 1987). This study included a sample of 24 patients with rheumatoid arthritis. They were divided into two groups (Group A and Group B) based on their DASH score and their primary medication. Group A (treatment group) received LLLT of the metacarpophalangeal (Mep) joints and proximal interphalangeal (PIP) joints of their more severely affected hand. Patients in Group B (placebo / M

CoordenaÃÃo de AperfeÃoamento de Pessoal de NÃvel Superior / Himatanthus drasticus à uma planta laticÃfera pertencente à famÃlia Apocynaceae encontrada na AmÃrica do Sul e conhecida popularmente como janaguba. Seu lÃtex à conhecido como âleite de janagubaâ e apresenta vÃrias atividades farmacolÃgicas. O presente trabalho teve como objetivo estudar o efeito das proteÃnas isoladas do lÃtex de Himatanthus drasticus (HdLP) em modelo de artrite experimental induzida por zymosan (Zy). A artrite foi induzida em camundongos machos swiss (n=6) atravÃs da administraÃÃo de 0,1 mg Zy i.a. Os animais foram tratados com HdLP (5 e 50 mg/kg i.v.) ou Salina i.v. 1 hora apÃs o Zy e com HdLP (50 mg/kg v.o.) ou Dexametasona (2 mg/kg s.c.) 1 hora antes do Zy. Seis horas apÃs a induÃÃo os animais foram eutanasiados, foi realizada a lavagem da articulaÃÃo e o lavado articular coletado para avaliaÃÃo do efeito de HdLP sobre a migraÃÃo de leucÃcitos, atividade da mieloperoxidase (MPO) e liberaÃÃo de mediadores inflamatÃrios (NO, TNF-&#945;, IL-1&#946;, IL-6 e IL-10). O edema foi avaliado pela mediÃÃo do diÃmetro transversal da articulaÃÃo e pela avaliaÃÃo da permeabilidade vascular. AlÃm disso, foi avaliado o efeito de HdLP sobre processo inflamatÃrio na membrana sinovial e sobre a hipernocicepÃÃo mecÃnica utilizando uma versÃo eletrÃnica (VonFrey). Para as anÃlises estatÃsticas foi utilizado o teste ANOVA/Bonferroni ou Kruskal Wallis/Dunns; p <0,05 foi considerado significante. Este estudo foi aprovado pela ComissÃo de Ãtica em Pesquisas com Animais da UFC - CEPA (38/14). HdLP 50 mg/kg i.v. apresentou uma diminuiÃÃo significativa na contagem de leucÃcitos, nos nÃveis de MPO e na liberaÃÃo de medidores inflamatÃrios (NO, IL-1&#946;, e IL-6). TambÃm foi observado uma diminuiÃÃo do edema e no dano à membrana sinovial. Na hipernocicepÃÃo mecÃnica os grupos (HdLP 50 mg/kg i.v. e 50 mg/kg v.o.) apresentaram um aumento no limiar nociceptivo. HdLP apresenta atividade antinociceptiva e anti-inflamatÃria no modelo de artrite induzida por Zy. O efeito parece estar relacionado com a diminuiÃÃo da migraÃÃo de neutrÃfilos e da liberaÃÃo de mediadores inflamatÃrios, reduzindo o dano na membrana sinovial e a hipernocicepÃÃo. / Himatanthus drasticus is a laticiferous plant of the family Apocynaceae found in South America and popularly known as janaguba. Your latex is known as "janaguba milk" and has several pharmacological activities. This work aimed to study the effect of isolated proteins from Himatanthus drasticus latex (HdLP) zymosan (Zy) induced arthritis. Arthritis was induced in male Swiss mice (n = 6) by administering 0.1 mg Zy intra-articular. The animals were treated with HdLP (5 and 50 mg/kg i.v.) or Saline i.v. 1 hour after the Zy and HdLP (50 mg/kg v.o.) or Dexamethasone (2 mg/kg s.c.) 1 hour before Zy. After six hours of induction the animals were euthanized, the joint washing carried, and collected for leukocyte count, determination of the myeloperoxidase (MPO) activity and inflammatory mediators (NO, TNF-&#945;, IL-1&#946;, IL-6 and IL-10). The edema was evaluated by measuring the diameter articular and the vascular permeabilitym through extravasation. In addition, we evaluated the effect of HdLP on synovial inflammation as well the mechanical hypernociception. For statistical analysis we used the ANOVA/Bonferroni or Kruskal Wallis/Dunns; p <0.05 considered significant. This study was approved by the Ethics Committee on Animal Research of the UFC - CEPA (38/14). HdLP (50 mg/kg i.v.) a significant decrease on the leukocyte count in MPO activity and levels (NO, IL-1&#946;, and IL-6). It was also observed a decrease in swelling and damage to the synovial membrane. The nociceptive threshold was increased by HdLP 50 mg/kg i.v. and 50 mg/kg v.o. HdLP has antinociceptive and anti-inflammatory activity in the model of arthritis induced by Zy. The effect seems to be related to the decreased migration of neutrophils and the release of inflammatory mediators, reducing damage to the synovial membrane and hypernociception.

A dissertation submitted in partial compliance with the requirements for the Master's Degree in technology: Chiropractic, Technikon Natal, 2001. / The purpose of this study was to evaluate the relative effectiveness of manipulation versus meloxicam (a Non-Steroidal Anti-Inflammatory Drug) to determine which is more beneficial in treating osteoarthritis of the knee. This was a prospective, randomized clinical trial consisting of a population of sixty voluntary subjects, diagnosed as suffering from osteoarthritis of the knee. The patients were divided equally into two groups of thirty, with Group A receiving chiropractic manipulative therapy on eight consultations over three weeks, and Group B receiving meloxicam 7,5mg tablets once daily for three weeks. Capturing of the subjective and objective data for both groups took place on the first, fourth and eighth consultations. Subjective data was captured using the Numerical Pain Rating scale-l 01, the Visual Analogue scale, as well as the Patient -Specific functional scale. Objective data was gathered from goniometric and pressure algometer measurements. / M

Introduction: Patients with inflammatory polyarthritis (IP) have an excess risk of cardiovascular (CVD) mortality due to accelerated atherosclerosis. Markers identifying individuals with subclinical atherosclerosis as measured by carotid intima-medial thickness (cIMT) and plaque may allow for attenuation of CVD risk. The objective of this study was to identify associated risk markers for atheromatous plaque and cIMT in an incident cohort of patients with early IP and to assess the risk markers associated with progression of cIMT and plaque after 2 years of follow-up.Methods: From 2004 to 2008 consecutive patients with early IP (≥2 joints swollen for ≥4 weeks) aged 18-65 years, who were within 24 months of symptom onset (±6 months) were recruited as part of a primary-care-based inception cohort. Apparently healthy controls were recruited on a frequency matched 'buddy' pair system. Patients underwent joint and blood pressure examination. Patients and controls underwent BMI measurement and their medication was recorded. Patients' blood was taken for measurement of rheumatoid factor, anti-citrullinated protein antibody, C reactive protein, glucose, lipids (LDL, HDL, triglycerides, paroxonase 1, apolipoprotein A1 and B) and markers of vascular damage (E-selectin, VCAM) and adipocytokines (leptin and adiponectin). Patients and controls underwent B mode Doppler ultrasound examination of the carotid arteries to assess for cIMT and the presence of plaque. In univariate analyses we identified factors that were associated with cIMT and plaque presence after age and gender adjustment. An additive stepwise multivariable logistic regression model was created to investigate the independence of any associations.Results: The 329 IP subjects had a median (IQR) age of 51 (42-58) years and 96 (29%) were male. IP subjects were more likely to be smokers, have a family history of CVD, have diabetes, higher BP and be overweight than their apparently healthy counterparts. IP subjects with plaque at baseline often did not have prior CVD. Subjects with IP had a 2.87 fold higher plaque frequency at the baseline but a similar median cIMT relative to the controls. Traditional CVD risk markers such as age, systolic BP and LDL were associated with cIMT and plaque at baseline. Adiponectin levels were negatively associated with cIMT and positively associated with plaque. IP subjects had a significant increase in their cIMT in the first 2 years of follow-up. The rate of progression of cIMT was 1.5-2.2 fold greater in IP than reported in the general population. Novel risk factors added to the model above and beyond traditional risk factors in predicting atherosclerosis. Steroid exposure at 2 years was associated with atherosclerosis progression.Conclusion: Markers known to be associated with atherosclerosis in the general population are associated with cIMT and plaque presence in early IP prior to established inflammatory disease and therapy. While cIMT in subjects and controls was the same at baseline there was an accelerated rate of progression of cIMT in IP subjects relative to that reported in the general population.

Juvenile idiopathic arthritis (JIA) is a common chronic disease of childhood. Children with JIA have lower peak oxygen consumption (V0₂ peak) than healthy children. In order to examine the cardiorespiratory response during aerobic exercise and the anaerobic to aerobic ratio (metabolic index), maximal exercise tests were performed in JIA subjects and age- and sex-matched controls (CON). Thirteen children aged 10 to 17 years with JIA and 9 CON participated. Peak powe r(watts, W) and total work (Joules, j) were determined with the Wingate anaerobic cycling test. VO₂ peak was measured by a maximal staged exercise test on a cycle ergometer. Cardiac output (CO, liters/minute) was measured with Doppler echocardiography. Arterial — mixed venous oxygen index (A-V0₂) and systemic vascular resistance (SVR) were calculated. Patient questionnaires included habitual activity, visual analog scale for joint pain and the childhood health assessment questionnaire. Physician completed data included active joint count and articular severity index. Compared to CON and reference age-matched norms, JIA subjects had lower aerobic fitness. VO₂ peak in JIA was 31.3 ml/min/kg (20.2-49.9), Z score -1.4 (-.06--2.4) and in CON was 47.9 ml/min/kg (32.7-54.1), Z score of -0.17 (-1.6-.87). [p = 0.013 V0₂ peak, p=0.011 Z score]. There were no significant differences in CO, A-V0₂ or SVR buttrends towards lower CO and higher SVR in JIA subjects were observed. During anaerobic exercise JIA subjects completed less total work (168.5 j/kg (107-252) JIA, 224 j/kg (180-248) CON, p=.036) but had similar peak power (9.7 W/kg (5.6-13.7) JIA, 11.3 W/kg (9.8-14.5) CON, p=.095). The metabolic index did not differ between JIA and CON. There was no significant correlation between disease activity, function and fitness measures in JIA subjects. Children with JIA have moderate impairments in aerobic fitness. CO and A-V0₂ during aerobic exercise did not significantly differ between JIA subjects and CON. Anaerobic fitness was mildly impaired with less total work completed by JIA subjects. Further research with larger numbers is required to determine factors contributing to limited fitness in JIA. / Education, Faculty of / Kinesiology, School of / Graduate

Because of the importance of medical and psychiatric information in diagnosis, there is a tendency to neglect or under-emphasize socio-economic information. This is partly an Issue of recording; but it may have vital bearing on rehabilitation, and perhaps on treatment, in the broadest sense of the term, related to prognosis and rehabilitation plans. This study undertakes an exploration of this area, for a sample group of male patients receiving residential treatment in an arthritis treatment centre (Canadian Arthritis and Rheumatism Society, Vancouver) from 1952-1955. The socio-economic factors examined were in three groups, (a) age (b) family and marital factors (c) employment and occupational status. The material used was obtained from medical and social service records of the agency. Statistical data were taken from admission forms and social service face sheets. Social service records provided the material concerning the attitudes and adjustments of the patients. Two broad categories of treatment goal used by the agency in planning treatment, (1) employ-ability, and (2) improved self-care were followed in the present study in assessing the patients’ adjustment following treatment. Judged from these results the team estimate of the rehabilitation potential of the patients was 72% accurate in spite of the many unknowns in the handling of rheumatoid arthritis. The duration of the illness before treatment, and the length of treatment, appeared less important in relation to degree of improvement than might have been expected. Chronological age is clearly important: there was marked difference in the response of the patients under 50 years of age, compared with the response of the older patients, whether the treatment goal was "employability” or "improved self-care”. The patient's general attitude toward employment seemed more influential than the type of work he was accustomed to do. The men whose inter-personal relationships were adjudged within normal range were best able to adjust to the trauma of illness, and to make best use of the rehabilitation service. The concept of team treatment is again demonstrated by this kind of study. The Social Worker as a member of the treatment team is shown to have responsibility in three areas: (a) direct treatment of the patients (b) inter-professional planning for the patients, and (c) the use of community resources. The study leads to some recommendations for the improvement of community and agency services, and suggests that study of social and economic needs of older men demands attention. / Arts, Faculty of / Social Work, School of / Graduate

The Canadian Arthritis and Rheumatism Society, British Columbia Division has envisaged research as an important and integral part of its objectives and in February 1951 embarked upon an intensive study of the usefulness of cortisone in long-term medical treatment of the rheumatic diseases, including a series on Rheumatoid Arthritis. A comprehensive program of medical treatment has been put into effect, including the services of social workers. It is essentially a team approach to the aim of physical rehabilitation and a return to gainful employment. The present study is directed to the evaluation of the case work treatment offered to those patients selected to participate in the Rheumatic Diseases Project, Rheumatoid Arthritis Series on Cortisone Therapy. Within a predominantly medical setting the function of the case worker has been considered from the viewpoint of what is expected of her by the medical profession and what might be expected from her as a professional social worker. Two methods of assessment were employed both based on evaluation of each case according to selected case work criteria and the premise that effectiveness of treatment depends upon the appropriate use of skills in relation to the degree of treatability of the patient. The first approach made use of the available case records as far as possible. The second was the device of a Rating Scale devised for the purpose and completed by a group of social workers for each patient worked with. The goals aimed at by the Medical Committee responsible for the project were stated as "physical rehabilitation and a return to gainful employment". Medically the cortisone therapy was successful in effecting enough physical improvement for a patient to become potentially employable. Socially results were discouraging because emotional difficulties and the non-availability of suitable positions prevented the actual return of many patients to gainful employment. The Long-standing personality problems, characterizing this group of patients, precluded the use of intensive case work techniques in roughly 75% of the cases. The evidence is that face-to-face interviewing involving the skilled use of relationship is not appropriate and that supportive technigues designed to prevent further deterioration, alone are relevant for the majority. Sound social diagnostic evaluations with the use of appropriate treatment methods are essential. It is suggested the reality of the team approach should he made available, and that more use should be made of social work skills in the selective screening of applicants for rehabilitation, and that the contributions of social work in the total team plan merits deeper exploration. / Arts, Faculty of / Social Work, School of / Graduate

Team members in medical rehabilitation centres are focusing more attention on devising new means for the establishment of a more precise evaluation of the patient's total functioning. The evaluation of the patient's social functioning is critical to team planning and treatment. It is also critical for the assessment of the success of the rehabilitation program. This experimental study was carried out under the joint auspices of the Vancouver branch of the Canadian Arthritis and Rheumatism Society and the School of Social Work at the University of British Columbia, in order to devise specific criteria for the assessment of the patient's social functioning. This in turn, would enable a more accurate assessment of the patient's total functioning. The study is limited to a small group of married female patients who received residential treatment at the Vancouver C.A.R.S. medical centre during the period between January 1962-May 1964. Role theory was used as the main frame of reference for this study and social functioning was equated to the sum total of roles performed. A three-point rating scale and scoring was created to represent the assessed performance of each role. An experimental approximation represented by a percentage figure was obtained of the subjects' social functioning levels at four specific points in time. Three sets of ratings were collected from (a) data found In the C.A.R.S. social service recordings, (b) data obtained from the subjects and (c) data collected by the writer from the subjects. The findings point out that although the research model demonstrated changes in levels of social functioning, these results were not conclusively established. The results were at best tentative, since the C.A.R.S. social service records could not meet the demands of the research instrument and the study involved only a small number of subjects. However, there was strong Indication that application of role theory to social functioning assessment formulations does provide a meaningful and systematic method for evaluating the patient's total functioning. In future sequential research, it has been recommended that social service records be utilized which employ role theory as the basis for social assessment formulations. Further, it has been suggested that one way to overcome the crudeness of the present research model, is to expand this study's three-point rating scale to a five-point rating scale, which would then reflect more accurately the patient’s social functioning. / Arts, Faculty of / Social Work, School of / Graduate