61. The effect of zinc and vitamin A supplementation on immune response in an older population.

Fortes C, Forastiere F, Agabiti N, Fano V, Pacifici R, Virgili F, Piras G, Guidi
L, Bartoloni C, Tricerri A, Zuccaro P, Ebrahim S, Perucci CA
National Institute of Health, Rome, Italy.
J Am Geriatr Soc 1998 Jan;46(1):19-26

OBJECTIVE: To determine if either supplemental vitamin A, zinc, or both increases cell-mediated immune response in an older population. DESIGN: A double-blind, randomized, controlled trial of supplementation with vitamin A and zinc. SETTING: Casa Di Riposo Roma III, a public home for older people in Rome, Italy. SUBJECTS: The health and nutritional status of 178 residents were evaluated. One hundred thirty-six residents agreed to participate in the trial and were randomized into four treatment groups, and 118 of these residents completed the trial. INTERVENTION: The four treatments consisted of: (1) Vitamin A (800 micrograms retinol palmitate); (2) Zinc (25 mg as zinc sulfate); (3) Vitamin A and Zinc (800 micrograms retinol palmitate and 25 mg as zinc sulfate); (4) Placebo capsules containing starch. MAIN OUTCOME MEASUREMENTS: Immune tests-counts of leucocytes, lymphocytes, T-cell subsets, and lymphocyte proliferative response to mitogens-were measured before and after supplementation. RESULTS: Zinc increased the number of CD4 + DR + T-cells (P = .016) and cytotoxic T-lymphocytes (P = .005). Subjects treated with vitamin A experienced a reduction in the number of CD3 + T-cells (P = .012) and CD4 + T-cells (P = .012). CONCLUSIONS: These data indicate that zinc supplementation improved cell-mediated immune response, whereas vitamin A had a deleterious effect in this older population. Further research is needed to clarify the clinical significance of these findings.

62. Dietary polyunsaturated fatty acids and inflammatory mediator production.

James MJ, Gibson RA, Cleland LG
Rheumatology Unit, Royal Adelaide Hospital, Adelaide, Australia, and the
Department of Pediatrics and Child Health, Flinders Medical Center, Bedford
Park, Australia.
Am J Clin Nutr 2000 Jan;71(1 Suppl):343S-8S

Many antiinflammatory pharmaceutical products inhibit the production of certain eicosanoids and cytokines and it is here that possibilities exist for therapies that incorporate n-3 and n-9 dietary fatty acids. The proinflammatory eicosanoids prostaglandin E(2) (PGE(2)) and leukotriene B(4) (LTB(4)) are derived from the n-6 fatty acid arachidonic acid (AA), which is maintained at high cellular concentrations by the high n-6 and low n-3 polyunsaturated fatty acid content of the modern Western diet. Flaxseed oil contains the 18-carbon n-3 fatty acid alpha-linolenic acid, which can be converted after ingestion to the 20-carbon n-3 fatty acid eicosapentaenoic acid (EPA). Fish oils contain both 20- and 22-carbon n-3 fatty acids, EPA and docosahexaenoic acid. EPA can act as a competitive inhibitor of AA conversion to PGE(2) and LTB(4), and decreased synthesis of one or both of these eicosanoids has been observed after inclusion of flaxseed oil or fish oil in the diet. Analogous to the effect of n-3 fatty acids, inclusion of the 20-carbon n-9 fatty acid eicosatrienoic acid in the diet also results in decreased synthesis of LTB(4). Regarding the proinflammatory ctyokines, tumor necrosis factor alpha and interleukin 1beta, studies of healthy volunteers and rheumatoid arthritis patients have shown < or = 90% inhibition of cytokine production after dietary supplementation with fish oil. Use of flaxseed oil in domestic food preparation also reduced production of these cytokines. Novel antiinflammatory therapies can be developed that take advantage of positive interactions between the dietary fats and existing or newly developed pharmaceutical products.

63. Xerostomia. A neglected symptom.

Sreebny LM, Valdini A
Arch Intern Med 1987 Jul;147(7):1333-7

Xerostomia, the subjective feeling of dry mouth caused by a severe reduction in the flow of saliva, is a common problem that is particularly prevalent among the aged. It has become increasingly evident that dry mouth is associated with a number of serious systemic conditions and diseases. Among these are the intake of commonly prescribed medications, autoimmune diseases, and irradiation to the head and neck. The diminution in the flow of saliva may profoundly affect oral health, disturb digestion and speech, and seriously impair the patient's quality of life. Food avoidance, nonabsorption of sublingually placed drugs, and noncompliance with medication may also result. Sialometry can be used to confirm the presence of dry mouth. Treatment is aimed at increasing the flow of saliva, when possible, or providing oral moisture by other means.

64. Sjogren's syndrome. More than dry eyes and dry mouth.

Smith DL, Lucas LM
Postgrad Med 1987 Jul;82(1):123-31

Sjogren's syndrome is a complex disease state with multisystem manifestations. Two forms of the disease, primary and secondary, are recognized; the secondary form is more easily diagnosed because of its association with an already established rheumatic or autoimmune disease. Treatment consists of measures to prevent damage from ocular and oral dryness (sicca complex) and to minimize systemic manifestations.

65. Overview of Sjogren's syndrome.

Talal N
J Dent Res 1987 Feb;66 Spec No:672-4

Sjogren's syndrome, a chronic inflammatory and autoimmune disorder (Shoenfeld and Schwartz, 1984; Smith and Steinberg, 1983), is characterized by diminished lacrimal and salivary gland secretion (sicca complex), resulting in keratoconjunctivitis sicca (KCS) and xerostomia. As originally described, the syndrome consisted of a triad of dry eyes, dry mouth, and rheumatoid arthritis. We now know that other connective tissue diseases (e.g., systemic lupus erythematosus, progressive systemic sclerosis, and polymyositis) may be present in place of rheumatoid arthritis, and that the sicca complex can exist as a primary pathologic entity with no associated disorder (Strand and Talal, 1980; Talal, 1985). Moreover, generalized lymphoproliferation, pseudolymphoma, or even lymphoid malignancy may appear in some patients (Talal and Bunim, 1964; Talal et al., 1967). More than 90% of patients are women, with a mean age of 50 years at diagnosis. The disease occurs in all races and all ages.

66. Physical fitness: benefits of exercise for the older patient. 2.

Butler RN, Davis R, Lewis CB, Nelson ME, Strauss E
Department of Geriatrics and Adult Development, Mount Sinai Medical Center, New
York, USA.
Geriatrics 1998 Oct;53(10):46, 49-52, 61-2

Exercise provides important benefits for older adults in the areas of cardiovascular function, strength and muscle mass, postural stability, and psychological function. These benefits can be achieved by those who are healthy, as well as by the frail and very old. Physicians can use a simple screening test to identify patients at risk for loss of mobility and function due to muscle weakness. Exercise helps prevent hip fractures from falls by increasing bone density, coordination, balance, and muscle strength. It is also an important treatment for patients with arthritis, Parkinson's disease, stroke, and other chronic diseases of aging. Patients who exercise show improvements in depressive symptoms and sleep disorders.

67. Reevaluation of laboratory parameters in relation to histological findings in primary and secondary Sjogren's syndrome.

Ohara T, Itoh Y, Itoh K
Department of Clinical Pathology, Jichi Medical School, Tochigi.
Intern Med 2000 Jun;39(6):457-63

OBJECTIVE: We reevaluated the diagnostic value of laboratory parameters in relation to histopathological findings in Sjogren's syndrome (SS) to clarify whether autoantibodies are useful diagnostic criteria for SS, and whether any laboratory data are useful in estimating the degree of salivary gland change. PATIENTS AND METHODS: Laboratory parameters and histopathological findings were analyzed in 96 patients examined by labial biopsy. RESULTS: The percentage of cases with positive assays of rheumatoid factor and anti-SS-A/Ro antibodies was significantly higher in Definite SS. Patients with dense mononuclear cell infiltration of salivary tissues also had higher titers of rheumatoid factor. No useful laboratory parameters were found for the diagnosis of secondary SS. CONCLUSION: Rheumatoid factor and anti-SS-A/Ro antibodies are useful for the diagnosis of primary SS, and rheumatoid factor is also an indicator of the severity of salivary glandular damage.

68. [Heredity and immunology in Sjogren's syndrome].

[Article in Norwegian]
Jonsson R, Nakken B, Halse AK, Skarstein K, Brokstad K, Haga HJ
Broegelmanns Forskningslaboratorium Armauer Hansens hus Haukeland Sykehus,
Bergen.
Tidsskr Nor Laegeforen 2000 Mar 10;120(7):811-4

BACKGROUND: Over the next 3-5 years, the rapid progress in genomic research will enable the discovery of many genes associated with the more common diseases. An example of such a common disease is the rheumatic disorder Sjogren's syndrome, an autoimmune disease. A more precise genetic explanation of the mechanism leading to Sjogren's syndrome remains to be given. MATERIAL AND METHODS: One way of investigating the disease related genes in such complex polygenic diseases is to perform linkage studies in families with two or more affected. Another possibility is to conduct association studies on trios (parents and affected child), case control studies, or other experimental designs. In association studies one is testing if an allele is significantly elevated among patients compared to controls, while in linkage analyses one finds subchromosomal regions that are significantly more often inherited by patients than by healthy family members. RESULTS: The most well defined genetic association in Sjogren's syndrome is currently related to different HLA alleles and their association with anti-Ro/SSA and anti-La/SSB autoantibodies. Additional genetic studies focusing on non-HLA regions are under way. INTERPRETATION: Increased genetic knowledge would allow optimisation of the diagnostic criteria as well as development of new and more effective treatment for Sjogren's syndrome, which causes substantial suffering for a large group of patients.

69. Anxiety and depression in patients with primary Sjogren's syndrome.

Valtysdottir ST, Gudbjornsson B, Lindqvist U, Hallgren R, Hetta J
Department of Medical Sciences, University Hospital, Uppsala, Sweden.
sigridur.valtysdottir@medicin.uu.se
J Rheumatol 2000 Jan;27(1):165-9

OBJECTIVE: To examine the degree of anxiety and depression and to assess well being and general symptoms in patients with primary Sjogren's syndrome (SS). METHODS: A standardized questionnaire, the Hospital Anxiety and Depression Scale, was used to examine the degree of anxiety and depression in patients with primary SS (n = 62) and in age matched healthy female controls. The Gothenburg quality of life instrument (GQOL) was used to assess well being and general symptoms. Patients with rheumatoid arthritis (RA; n = 38) were used as patient controls. RESULTS: The patients with primary SS had significantly higher scoring rate for "possible" clinical anxiety (48%) and for "possible" clinical depression (32%) compared with reference groups (p<0.05). The physical and mental well being of the patients with primary SS were significantly reduced compared with controls. Furthermore, patients with primary SS complained more commonly of low mood, irritability, headache, gastrointestinal symptoms, and impaired concentration and memory than the patients with RA. CONCLUSION: The results indicate that patients with primary SS often have psychiatric symptoms and worse well being, which may affect their quality of life.

70. Single-blinded controlled trial of low-dose oral IFN-alpha for the treatment of xerostomia in patients with Sjogren's syndrome.

Shiozawa S, Tanaka Y, Shiozawa K
Kobe University Hospital School of Medicine, Faculty of Health Science, and
Kakogawa National Hospital, Japan. shiozawa@ams.kobe-u.ac.jp
J Interferon Cytokine Res 1998 Apr;18(4):255-62

A single-blinded controlled trial was conducted to test the efficacy of low-dose oral human interferon-alpha (IFN-alpha) to improve salivary function in patients with Sjogren's syndrome. Fifty-six outpatients with primary and 4 patients with secondary Sjogren's syndrome were assigned randomly into treatment groups of either IFN-alpha or sucralfate (control). The IFN-alpha (150 IU) or sucralfate (250 mg) was given orally three times a day for 6 months. Saliva was quantitated monthly by the Saxon test. After 6 months of treatment, 15 of 30 (50%) IFN-alpha-treated patients had saliva production increases at least 100% above baseline, whereas only 1 of 30 (3.3%) sucralfate patients had a comparable increase (p < 0.001). The increase in saliva production, by treatment group, was significantly greater (p < 0.01) in the IFN-alpha treated group at every month after treatment. Serial labial salivary gland biopsies of 9 IFN-alpha responder patients showed that lymphocytic infiltration was significantly decreased (p < 0.02) and the proportion of intact salivary gland tissue was significantly increased (p = 0.004) after the IFN-alpha treatment. In this study, IFN-alpha therapy significantly improved Sjogren's syndrome salivary gland dysfunction.

71. [Cyclosporin in autoimmune diseases].

Frey FJ
Medizinische Poliklinik, Inselspital Bern.
Schweiz Med Wochenschr 1990 May 26;120(21):772-86

The efficacy of cyclosporine (Sandimmun) is well established in the field of organ transplantation. More recently, prospective controlled trials were performed in patients with other diseases. The efficacy of cyclosporine for the following clinical entities was proven by the trials: endogenous uveitis, rheumatoid arthritis, Sjogren's syndrome, myasthenia gravis, psoriasis and Crohn's disease. Furthermore, there is evidence from a controlled trial of some benefit for patients with aplastic anemia. The proteinuria of patients with glomerulonephritis was reduced by cyclosporine, though no improvement in glomerular filtration rate was observed. Large controlled trials in patients with multiple sclerosis or amyotrophic lateral sclerosis revealed a beneficial effect on some clinical parameters. Nevertheless, cyclosporine cannot be recommended for these patients at the present time, since the ratio between the (slight) beneficial effects and the side effects was unfavourable. In patients with primary biliary cirrhosis, cholestasis slightly diminished after the administration of cyclosporine. Whether this improvement in laboratory parameters predicts an improved outcome in patients with primary biliary cirrhosis has yet to be demonstrated. Some patients with recently diagnosed insulin dependent diabetes needed no further insulin therapy as long as cyclosporine was administered. This is an observation of tremendous potential practical relevance for the future, when methodology may be available for diagnosing autoimmune destruction of beta-cells before clinically overt diabetes is present. Cyclosporine combined with prednisone was slightly more efficacious in patients with Graves' ophthalmopathy than prednisone alone. For all other autoimmune diseases, no controlled studies with cyclosporine are available at the present time. The most important side effects of cyclosporine are renal dysfunction, hypertension, gout, tremor, gingival hyperplasia and hypertrichosis. These side effects are manageable by appropriate dosage of cyclosporine and prophylactic measures. Side effects caused interruption of cyclosporine therapy in less than 5% of the patients. Thus, cyclosporine appears to be an efficacious new agent for treatment of some groups of patient with immune diseases.

72. Lipid imbalance involving the essential fatty acids was suggested as a possible factor in SS.

United Kingdom study, published in Medical Hypotheses (1991).

73. Sjogren's syndrome. Dental role in providing relief.

Sciubba JJ, Mandel ID
Department of Dental Medicine, Long Island Jewish Medical Center, New Hyde Park.
N Y State Dent J 1992 Aug-Sep;58(7):39-42

This oftentimes underappreciated disease carries with it severe dental implications, all of which can affect the patient's quality of life. While there is no cure, it is possible to manage disease symptoms and to prevent irreversible dental damage.

74. Effect of Bakumondo?to on salivary secretion in patients with Sjogren's syndrome.

Jpn J Rheumatology 1992;4(2):91?101.