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Biomedical subjects

M Tishler

Publications and source records attributed to M Tishler.

At least 19 recordsLinked to original sources

Hyperbaric oxygen therapy for nonhealing vasculitic ulcers.

BACKGROUND: Cutaneous nonhealing ulceration is a threatening manifestation of vasculitis. Hyperbaric oxygen (HBO), frequently used as adjuvant therapy for patients with ischaemic ulcers, exerts additional beneficial effects on the vascular inflammatory response. AIM: To evaluate the effect of HBO on vasculitis-induced nonhealing skin ulcers. METHODS: The study population comprised 35 patients aged >or= 18 years with severe, nonhealing, vasculitis-induced ulcers that had not improved following immunosuppressive therapy. Baseline ulcer tissue oxygenation was evaluated at room air concentration (21% O2), at 1 atmosphere absolute (ATA) breathing 100% O2, and at 2 ATA breathing 100% O2. The baseline treatment protocol consisted of a 4-week course of 100% O2 for 90 min at 2 ATA, five times/week. RESULTS: The mean baseline ulcer tissue oxygenation (3.1 +/- 2.4 kPa at room air concentration), was significantly increased to 13.9 +/- 11.9 kPa at 1 ATA breathing 100% O2 (P < 0.001), and subsequently increased further to 59.1 +/- 29.8 kPa at 2 ATA breathing 100% O2 (P < 0.001). At the end of the hyperbaric therapy, 28 patients (80%) demonstrated complete healing, 4 (11.4%) had partial healing and 3 (8.6%) had no improvement. None of the patients had any side-effects related to the HBO therapy. CONCLUSION: HBO therapy may serve as an effective safe treatment for patients with vasculitis having nonhealing skin ulcers. Further studies are needed to evaluate its role as primary therapy for this group of patients.

Adult↗

Clinical and immunological characteristics of elderly onset Sjögren's syndrome: a comparison with younger onset disease.

OBJECTIVE: To compare the clinical and laboratory characteristics of patients with primary Sjögren's syndrome (SS) with an elderly onset to those with a younger onset. METHODS: The study group comprised 85 consecutive patients (79 women and 6 men) attending the Sjögren's clinic. Primary SS was diagnosed according to the San Diego criteria. Elderly onset disease (EOD) was determined as the appearance of symptoms suggestive of SS after age 65. Clinical and laboratory variables for EOD were compared to those of a younger onset disease (YOD). Salivary and serum samples of all patients were examined for concentrations of interleukin 6 (IL-6) and hyaluronic acid (HA). RESULTS: Seventeen patients with SS (20%) matched the definition of EOD and their median disease onset was 71 years (range 65-80). No significant differences were noted in the clinical disease manifestations between the 2 groups of patients. Rheumatoid factor and anti-Ro(SSA) antibodies were more common in the YOD group (p = 0.012 and p = 0.023, respectively). Significant elevations of salivary IL-6 and HA levels were detected in the YOD group compared to the EOD group with SS (17.3 +/- 3.6 vs 8.8 +/- 2.1 pg/ml and 230.2 +/- 41.1 vs 128.8 +/- 33.3 ng/ml, respectively) (p < 0.0001). CONCLUSION: EOD SS has somewhat milder clinical symptoms with fewer immunological manifestations than YOD. The elevations of salivary IL-6 and HA in the younger group of SS patients support in part the differences in the inflammatory process between the 2 groups.

Adult↗

Increased salivary interleukin-6 levels in patients with primary Sjögren's syndrome.

This study's purpose was to evaluate salivary interleukin-6 (IL-6) levels in patients with primary Sjögren's syndrome (SS). Salivary and serum IL-6 concentrations were evaluated by ELISA in 36 patients with SS and compared with 19 patients complaining of dry mouth and with normal controls. Salivary IL-6 levels were significantly elevated (P < 0.01) in the 36 patients with SS as compared to the 19 patients with dry mouth (200.5 +/- 43.6 and 12.6 +/- 6.8 pg/ml, respectively). No significant differences were noted in the serum IL-6 levels between these two groups (105.8 +/- 17.1 and 84.8 +/- 17.1 pg/ml, respectively). Both salivary and serum IL-6 levels in the normal controls were below the level of detection of the assay. Positive correlation (r = 0.8613, P < 0.0001) was found between salivary IL-6 levels and the focus score of labial biopsies in SS patients. Elevated salivary IL-6 levels appear to be a consequence of local production and may reflect the component of salivary gland inflammation in SS.

Aged↗

Salivary and serum soluble interleukin-2 receptor in primary Sjögren's syndrome.

Salivary and serum concentrations of soluble interleukin-2 receptor (sIL-2R) were studied in a group of patients with Sjögren's syndrome and a group suffering from dry mouth. Salivary sIL-2R levels was significantly higher (57.9+/-15.1 vs 16.7+/-4.7 pg/ml) (p < 0.05) in the group of 26 patients with Sjögren's syndrome than in the dry-mouth group. Both the salivary and the serum sIL-2R of normal controls were below the level of detection. No significantly statistical differences were noted between the concentrations of serum sIL-2R in either abnormal groups. No correlations were found between salivary or serum sIL-2R and the erythrocyte sedimentation rate, C-reactive protein, the presence of various autoantibodies or the focus score from lip biopsies in the group of patients with Sjögren's syndrome. The results show that, although the salivary sIL-2R does not actually reflect the extent of inflammation, it might have an important role in the diagnosis of Sjögren's syndrome.

Autoantibodies↗

Hydroxychloroquine treatment for primary Sjögren's syndrome: its effect on salivary and serum inflammatory markers.

OBJECTIVE: To evaluate the effect of hydroxychloroquine treatment on interleukin 6 (IL6), hyaluronic acid (HA), and soluble interleukin 2 receptor (sIL2R) concentrations in the saliva and serum of patients with primary Sjögren's syndrome (SS). METHODS: Fourteen SS patients treated with hydroxychloroquine 200 mg/day for 12 months were investigated in an open prospective study. Clinical parameters of efficacy and routine biochemical and haematological data to assess drug safety and tolerability were determined every three months. Salivary and serum IL6, sIL2R, and HA values were determined at study entry, 6 and 12 months, using ELISA and radiometric assays. RESULTS: After hydroxychloroquine treatment, salivary IL6 concentrations decreased from 13.2 (1.2) to 7.3 (1.1) pg/ml (mean (SEM)) (p < 0.0001). Similarly, salivary HA concentrations were also reduced from 577.8 (120) to 200 (34) ng/ml (mean (SEM) (p < 0.003). Serum IL6 concentrations decreased from 5.4 (0.6) to 2.9 (0.2) pg/ml (mean (SEM) (p < 0.001), while serum HA concentrations remained unchanged. No change has been detected in salivary or serum sIL2R concentrations after 12 months of treatment with hydroxychloroquine. Treatment also resulted in significant reduction in erythrocyte sedimentation rate, serum gamma globulin, and C reactive protein values while only partial clinical improvement was noted in some patients. A more pronounced decrease of salivary IL6 and HA levels was found in the two patients in whom a reduction in the swelling of the parotid gland was noted. CONCLUSION: In this open label study of hydroxychloroquine treatment for SS a significant reduction of some salivary inflammatory markers was seen at the end of 12 months. Although during the treatment period only a partial clinical effect could be noted, the findings suggest that a double blind controlled study of hydroxychloroquine in SS is indicated.

Antirheumatic Agents↗

Elevated tear interleukin-6 levels in patients with Sjögren syndrome.

OBJECTIVE: The purpose of the study was to investigate interleukin-6 (IL-6) levels in the tear fluid and sera of patients with Sjögren syndrome (SS). PARTICIPANTS: Twelve patients with primary SS and 12 normal control subjects participated. INTERVENTION: Tear fluid and sera were obtained from the study and the control groups. Evaluation of tear fluid and sera IL-6 levels was done by using a quantitative enzyme-linked immunosorbent assay kit. All assays were carried out blindly with respect to diagnosis. MAIN OUTCOME MEASURES: Tear fluid IL-6 levels were measured. RESULTS: The mean concentration (+/- standard error) of IL-6 in the tears of patients with SS was elevated significantly compared to that of normal control subjects (88.6+/-16.2 vs. 42.1+/-10.6 pg/ml; P < 0.05). No significant differences were noted in the serum IL-6 levels between the two groups. A significant correlation (r = 0.742, P = 0.006) was found between tear fluid IL-6 levels and the focus score of lip biopsy specimens in patients with SS. CONCLUSION: Tear fluid IL-6 levels may serve as an important marker for tear gland involvement in SS.

Biomarkers↗

Allergic disorders in primary Sjögren's syndrome.

Allergic disorders have been described in a variety of connective tissue disorders. Although an association between allergy and primary Sjögren's syndrome has been suggested, it has not been well documented. The purpose of this study was to analyze the prevalence of several types of allergic disorders in a cohort of primary Sjögren's syndrome patients. The presence of an allergic disorder was evaluated by a specific questionnaire in 65 randomly selected primary Sjögren's syndrome patients and was compared to control groups of 67 rheumatoid arthritis patients, 53 patients with rheumatoid arthritis and sicca symptoms, and 31 patients with osteoarthritis. At least one type of allergic manifestation was reported by 42 of the 65 Sjögren's syndrome patients (65%). This rate was significantly higher than each of the three control groups (p < 0.01). Only drug allergy and skin contact allergy were found to be more prevalent in Sjögren's syndrome patients than in the control groups (p< 0.05). Allergic reactions were more common in Sjögren's syndrome patients who were anti-Ro positive (p < 0.05). As drug and skin contact allergies are a frequent finding in Sjögren's syndrome patients, obtaining a careful history is needed before prescribing drugs in these patients.

Adult↗

Salivary and serum hyaluronic acid concentrations in patients with Sjögren's syndrome.

OBJECTIVE: To evaluate salivary hyaluronic acid (HA) concentration in patients with primary Sjögren's syndrome (SS). METHODS: Salivary and serum HA concentrations were evaluated using a radiometric assay. Thirty nine patients with SS served as the study group and their results were compared with 19 patients having clinical symptoms and signs of dry mouth and with 10 normal controls. RESULTS: Salivary HA concentrations were significantly increased (p < 0.05) in the 39 patients with SS compared with the 19 patients with dry mouth and the 10 normal controls (240.7 (38.5) v 99.8 (14.6) and 91.3 (7.9) ng/ml, respectively) (mean (SEM)). No significant differences were noted in the serum HA concentrations between the three groups (42 (3.9) v 36.3 (4.1) and 32 (4.3) ng/ml, respectively) (mean (SEM)). No correlation could be found between salivary HA concentrations and the focus score of lip biopsies, nor between salivary HA concentrations and erythrocyte sedimentation rate or other serological tests. CONCLUSION: Increased salivary HA concentrations can serve as a marker of local inflammation and may be of value in the diagnosis of SS.

Adult↗

Anti-Ro (SSA) antibodies in rheumatoid arthritis patients with gold-induced side effects.

The purpose of our study was to investigate the significance of the presence of anti-Ro antibodies found by us in an earlier study of rheumatoid arthritis (RA) patients with gold-induced side effects. Sera of 29 anti-Ro (SSA) positive RA patients who had gold-induced side effects were studied. All sera were examined by Western blot using recombinant antigens, encoding the Ro 60 kD and the La proteins. HLA typing was done in all patients. Thirteen patients reacted only with the Ro 52 kD antigen and all had severe skin eruptions caused by gold therapy. Another ten patients who reacted only with the Ro 60 kD antigen had other side effects to gold (six had proteinuria and four leucopenia). Six patients who reacted to all three antigens (Ro 52 kD, Ro 60 kD and La) had secondary Sjögren's syndrome. No significant statistical differences were noted in the incidence of HLA-DR3 between the subgroups of patients. Our data indicated that antibodies to the Ro 52 kD antigen are associated with skin eruptions in RA patients treated with gold.

Aged↗

Antiperinuclear factor--clinical, serological and genetic correlates in Israeli patients with rheumatoid arthritis.

The possible association between the presence of antiperinuclear factor (APF) and clinical and genetic parameters was investigated in 54 Israeli patients with rheumatoid arthritis (RA). Rheumatoid factor (RF) was detected in the sera of 43 patients (80%) and APF was positive in 33 (61%). No significant statistical differences were found in the presence of HLA-DR4 and/or DR1 between APF-positive and -negative patients. Furthermore, neither the Ritchie articular index nor the patient's functional class correlated with the presence of APF. The results of our study suggested that although Israeli patients have a different genetic background, the presence and behaviour of APF is similar to that of other Caucasian populations.

Adult↗

Saliva: an additional diagnostic tool in Sjögren's syndrome.

OBJECTIVE: To assess the available data and the place of salivary analysis in the diagnosis of Sjögren's syndrome (SS). METHODS: A Medline search of English language articles published between 1985 and 1996 and a manual search of the reference lists of relevant articles formed the data sources. These were combined with our clinical and experimental experience in this field. Each method of salivary analysis was assessed according to study design, type of saliva used for the study, sensitivity/ specificity for the diagnosis of SS, and correlation to the histopathological findings. RESULTS: Increased levels of salivary Na+, immunoglobulins (particularly IgA), anti-Ro and La antibodies, lactoferrin, lysozyme, beta 2 microglobulin, prostaglandin E2, thromboxane B2, interleukin-6, and hyaluronic acid have been detected in various studies. Results varied according to the different methods used for saliva collection. CONCLUSION: Although many changes have been detected in various constituents of saliva in SS patients, no test has proved sensitive or specific enough for diagnosing SS.

Autoantibodies↗

The absorption of low-dose methotrexate in patients with inflammatory bowel disease.

BACKGROUND: Recent clinical trials have demonstrated that methotrexate may have an important therapeutic role in the treatment of patients with inflammatory bowel disease, who are either refractory or intolerant to traditional medical therapy. The aim of this study was to evaluate the pharmacokinetics of low-dose oral methotrexate in patients with inflammatory bowel disease. METHODS: Methotrexate (12.5 mg) was given orally to nine patients with inflammatory bowel disease: five with Crohn's disease, and four with ulcerative colitis, and to six patients with rheumatoid arthritis who served as a control group. Blood samples were drawn at specific intervals to evaluate methotrexate plasma levels. RESULTS: Methotrexate was rapidly absorbed in all patients. Peak concentrations (Cmax) varied considerably, ranging from 0.25-0.87 micro M. The mean Cmax values were similar in all patient groups (0.59 +/- 0.12, 0.69 +/- 0.16 and 0.54 +/- 0.18 micro M, P not significant) for Crohn's disease, ulcerative colitis and rheumatoid arthritis, respectively. The mean area under curve in 120 min (AUC0-120) was also similar in all patient groups (32.9 + 11.3, 43.6 + 9.9 and 41.8 + 14.9 ng.min/mL, P not significant) for Crohn's disease, ulcerative colitis and rheumatoid arthritis, respectively. The mean time to reach Cmax, (tmax), varied between patient groups (84, 112 and 95 min, respectively, with a significant difference, P < 0.02, between the Crohn's disease and ulcerative colitis groups. A negative correlation was found between methotrexate dosage/kg and Cmax (r = -0.74) only in Crohn's disease patients but not in the other patient groups. CONCLUSIONS: Orally administered methotrexate is well absorbed in patients with inflammatory bowel disease including those with severe small bowel disease or resection. If methotrexate is proven to be effective in inflammatory bowel disease, it should be administered orally.

Adult↗

Anti-heat-shock protein antibodies in rheumatic and autoimmune diseases.

The heat-shock proteins (hsp) are a family of molecules that have different molecular weights and are thought to operate as scavengers that trap abnormal proteins and protect the stressed cells. These molecules, which have been conserved during evolution, have highly identical stretches of their amino acid sequence in bacteria as well as in humans. Experiments show that arthritis patients manifest T-cell responses to the hsp-65-kD molecule, as do rats with adjuvant arthritis. The B cell response to hsp has not been extensively studied. Autoantibodies against hsp 65, 70, and 90 have been detected in various rheumatic and autoimmune disorders such as rheumatoid arthritis, ankylosing spondylitis, systemic lupus erythematosus, and inflammatory bowel diseases. The frequency of these antibodies varies among studies and is mainly dependent on the methods of detection. Studies on sensitivity and specificity of these antibodies do not exist; therefore, their significance should be interpreted cautiously.

Animals↗