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Biomedical subjects

Itzhak Rosner

Publications and source records attributed to Itzhak Rosner.

At least 19 recordsLinked to original sources

Prevalence and clinical aspects of Behcet's disease in the north of Israel.

Behcet's disease (BD) has a higher prevalence in countries along the ancient silk route, but the actual prevalence in Israel is unknown. We evaluated the occurrence and clinical expression of BD in the northern region of Israel: in the whole population and by ethnic groups. The sample included all adult patients with BD (International Study Group criteria) treated at three medical centers in northern Israel. Patient data were collected by file review and physician survey. Relevant demographic data for the population served by the medical centers were obtained from the official Israeli authorities. A total of 112 patients were identified. The overall prevalence of BD was 15.2/100,000 and was similar in men and women. The prevalence rates among the Jewish, Arab, and Druze populations were 8.6, 26.2, and 146.4 per 100,000, respectively. Age at disease onset was similar in all ethnic groups and significantly lower in males (28.6+/-9.7 vs 32.9+/-11.3, p=0.03). There were no differences in disease manifestations by sex or ethnicity. All Druze patients were HLA-B5 positive, compared to 80.8% of the Arab patients and 72.0% of the Jewish patients. Recurrent oral ulcers in family members were more common in Arab patients (p=0.004). The BD severity index was significantly lower in Druze patients (p=0.05), mainly in males (p=0.03). This study confirms the high prevalence of BD in Israel and the variability in disease rates and expression by ethnic origin. Our findings, particularly regarding the Druze population, call for further field surveys and genetic studies.

Adult↗

LPS-stimulated production of TNF-alpha by peripheral blood monocytes in patients with Behcet's disease.

Tumor necrosis factor alpha (TNF-alpha) is believed to play a significant role in disease pathogenesis of Behcet's disease (BD). High serum levels of TNF-alpha were repeatedly reported in patients with active BD and anti-TNF agents are effective in its treatment. The pathophysiology of TNF-alpha in BD is still unknown and conflicting results regarding TNF-alpha overproduction by peripheral blood monocytes (PBM) from patients with BD were reported. The aim of the study is to compare stimulated production of TNF-alpha by PBM of BD patients with that of healthy volunteers (HV) and to examine correlations between the ability of PBM to produce TNF-alpha and organ/system involvement in patients with BD. Eighteen patients with BD (mean age 38.4+/-12.4 years, 12 males) gave informed consent and completed the European BD Current Activity Form. The PBM were separated and treated with lipopolysaccharide (LPS) overnight. TNF-alpha levels in the supernatants were assayed by ELISA and values were expressed in terms of cell protein contents. The control group included 15 HV (mean age 34.2+/-9.9 years, seven males). The mean production of TNF-alpha/cell protein (ng/mg) and in-group dispersion were similar in both groups (p=0.98). In the subgroup analysis, TNF-alpha production by PBM in BD patients who reported "bad" or "very bad" global well-being over the last month (n=4) was higher compared to other patients with better self-rating (p=0.03). PBM of BD patients in the present study did not overproduce TNF-alpha upon stimulation with LPS. However, BD patients with a higher TNF-alpha-producing capacity had worse sense of well-being.

Adult↗

Gottron's papules-like eruption developing under hydroxyurea therapy.

A 57-year-old white female developed a Gottron's papules (GP)-like eruption, without any of the other clinical or laboratory signs of dermatomyositis (DM). She was under hydroxyurea treatment for chronic myeloid leukemia at the time. Skin biopsy was compatible with seborrheic keratosis. Conditions presenting with GP but unrelated to DM are reviewed, with emphasis on hydroxyurea-induced skin lesions.

Biopsy↗

Shortened QT interval: a distinctive feature of the dysautonomia of chronic fatigue syndrome.

PURPOSE: Because autonomic nervous functioning is frequently abnormal in chronic fatigue syndrome (CFS), we examined whether the corrected QT interval (QTc) in CFS differs from QTc in other populations. METHODS: The QTc was calculated at the end of 10 minutes of recumbence and the end of 10 minutes of head-up tilt. In a pilot study, groups of 15 subjects, CFS, and controls, matched for age and sex, were investigated. In a second phase of the study, the QTc was measured in larger groups of CFS (n = 30) and control patients (n = 96) not matched for demographic features. RESULTS: In the pilot study, the average supine QTc in CFS was 0.371 +/- 0.02 seconds and QTc on tilt, 0.385 +/- 0.02 seconds, significantly shorter than in controls (P = .0002 and .0003, respectively). Results of phase II confirmed this data. CONCLUSIONS: Relative short QTc intervals are features of the CFS-related dysautonomia. The significance of this finding is discussed.

Adult↗

Patterns of hypocapnia on tilt in patients with fibromyalgia, chronic fatigue syndrome, nonspecific dizziness, and neurally mediated syncope.

OBJECTIVES: To assess whether head-up tilt-induced hyperventilation is seen more often in patients with chronic fatigue syndrome (CFS), fibromyalgia, dizziness, or neurally mediated syncope (NMS) as compared to healthy subjects or those with familial Mediterranean fever (FMF). PATIENTS AND METHODS: A total of 585 patients were assessed with a 10-minute supine, 30-minute head-up tilt test combined with capnography. Experimental groups included CFS (n = 90), non-CFS fatigue (n = 50), fibromyalgia (n = 70), nonspecific dizziness (n = 75), and NMS (n =160); control groups were FMF (n = 90) and healthy (n = 50). Hypocapnia, the objective measure of hyperventilation, was diagnosed when end-tidal pressure of CO2 (PETCO2) less than 30 mm Hg was recorded consecutively for 10 minutes or longer. When tilting was discontinued because of syncope, one PETCO2 measurement of 25 or less was accepted as hyperventilation. RESULTS: Hypocapnia was diagnosed on tilt test in 9% to 27% of patients with fibromyalgia, CFS, dizziness, and NMS versus 0% to 2% of control subjects. Three patterns of hypocapnia were recognized: supine hypocapnia (n = 14), sustained hypocapnia on tilt (n = 76), and mixed hypotensive-hypocapnic events (n = 80). Hypocapnia associated with postural tachycardia syndrome (POTS) occurred in 8 of 41 patients. CONCLUSIONS: Hyperventilation appears to be the major abnormal response to postural challenge in sustained hypocapnia but possibly merely an epiphenomenon in hypotensive-hypocapnic events. Our study does not support an essential role for hypocapnia in NMS or in postural symptoms associated with POTS. Because unrecognized hypocapnia is common in CFS, fibromyalgia, and nonspecific dizziness, capnography should be a part of the evaluation of patients with such conditions.

Adult↗

Predicting outcomes on head-up tilt based on orthostatic hypotension patterns.

OBJECTIVE: To assess the frequency of different orthostatic hypotension (OH) patterns in patients having supine hypertension with OH ('SHOH') versus patients with OH and normal supine blood pressure ('OH alone'); and to relate OH patterns with outcomes on head-up tilt. METHODS: Consecutive patients with nonspecific dizziness were studied with a 10-min supine, 30-min head-up tilt test. Supine hypertension was diagnosed when supine systolic blood pressure (SBP) was at least 140 mmHg and/or supine diastolic blood pressure was at least 90 mmHg. OH was defined as SBP reduction of at least 20 mmHg within 3 min of tilt. OH patterns were identified corresponding to SBP time-curves during the initial 5 min of tilt: progressive, sustained and transient patterns. RESULTS: Among 400 patients tested, 31 had 'SHOH' and 39 had 'OH alone'. Frequencies of OH patterns were similar in both groups. The progressive OH pattern predicted symptomatic hypotension, leading to early tilt termination in all 'SHOH' and 88% of 'OH alone' patients. In comparison, tilt was early terminated in 33-48% of patients with sustained OH, transient OH and without OH. Early tilt termination was unrelated to age, gender, magnitude of supine SBP, pulse pressure and nadir SBP within 5 min tilt. CONCLUSIONS: Five minutes of postural challenge permitted assessing OH patterns. Outcome on protracted tilt was related to OH patterns, the worse outcome being likened to progressive OH, both in patients with 'SHOH' and in patients with 'OH alone'. Future studies will show whether OH patterns may serve as guidance for blood pressure therapy in selected patients.

Adult↗

Polyarthritis flare complicating rheumatoid arthritis infliximab therapy: a paradoxic adverse reaction.

BACKGROUND: The treatment of rheumatoid arthritis (RA) has changed dramatically over the past decade with the introduction of antitumor necrosis factor (anti-TNF) agents. Although subsets of patients may have only partial or no response, there is no report yet on possible worsening of RA with this therapy. OBJECTIVE: The objective of this study was to determine whether infliximab may paradoxically exacerbate RA. METHODS: One hundred seven patients with RA refractory to 3 disease-modifying antirheumatic drugs were treated with 3 mg/kg infliximab and methotrexate for at least 6 months. RESULTS: In 3 patients, there was an exacerbation of RA associated with the use of infliximab. The flare occurred during the first 6 to 12 months of treatment with polyarthritis, fever, and elevated acute phase reactants. Increase of infliximab dose resulted in further deterioration. CONCLUSION: We describe a paradoxic reaction, an exacerbation of RA, with infliximab. The mechanism of this side effect is unclear but may be related to altered immunity induced by the inhibition of TNF activity in predisposed patients.

Aged↗

Sjögren's syndrome in the community: can serology replace salivary gland biopsy?

BACKGROUND: It is relatively difficult in a community setting to perform salivary gland biopsy or reliable diagnostic tests for salivary gland involvement in a patient suspected to suffer from Sjögren's syndrome (SS). OBJECTIVE: To investigate whether anti-Ro/La antibodies are a good substitute for salivary gland biopsy in community patients suspected to suffer from SS. METHODS: Forty-one patients suspected as having SS due to dry eyes and mouth, articular complaints, and/or serological findings were examined for the presence of anti-Ro/La, and underwent minor salivary gland biopsy. RESULTS: Sixteen patients (39%) were classified as primary SS by the American-European Consensus Group criteria. Twelve subjects had anti-Ro/La antibodies and 11 subjects in this group had positive biopsy findings. Of 29 patients without anti-Ro/La antibodies, only four manifested positive biopsy findings. A significant association was found between the presence of anti-Ro/La antibodies and positive salivary gland findings characteristic for SS (p<0.0001, Fisher's exact test). CONCLUSION: These findings tend to support the suggestion that a patient suspected to suffer from SS in a community setting may be first tested for the presence of anti-Ro/La antibodies to confirm the diagnosis. Only those with a negative result for the presence of anti-Ro/La antibodies need to be referred for salivary gland biopsy.

Antibodies, Antinuclear↗

Calcinosis in rheumatic diseases.

BACKGROUND: Calcinosis, or dystrophic soft-tissue calcification, occurs in damaged or devitalized tissues in the presence of normal calcium/phosphorus metabolism. It is often noted in the subcutaneous tissues of connective tissues diseases--primarily systemic lupus erythematosus, scleroderma, or dermatomyositis--and may involve a relatively localized area or be widespread. The calcinotic accumulations may lead secondarily to muscle atrophy, joint contractures, and skin ulceration complicated by recurrent episodes of local inflammation and infection. OBJECTIVES: To review the classification, pathogenesis, clinical features, and treatment of calcinosis in rheumatic diseases. METHOD: A MEDLINE search of articles from 1972 to 2004 was conducted utilizing the index word "calcinosis" with the coindexing terms "scleroderma," "lupus," "dermatomyositis," and "dystrophic calcification." RESULTS: Calcinosis may be the source of both pain and disability in connective tissue disease patients. Illustrative cases of patients with severe calcinosis are described. The literature available was critically reviewed. While warfarin, colchicine, probenecid, bisphosphonates, diltiazem, minocycline, aluminum hydroxide, salicylate, surgical extirpation, and carbon dioxide laser therapies have been used, no treatment has convincingly prevented or reduced calcinosis. CONCLUSIONS: Calcinosis is common in the conditions reviewed and a number of agents have been used for treatment. However, the approach to calcinosis management is disorganized, beginning with the lack of a generally accepted classification and continuing with a lack of systematic study and clinical therapeutic trials.

Adult↗

Search for disease-specific cardiovascular reactivity patterns: developing the methodology.

Aberrations of CVR (cardiovascular reactivity), an expression of autonomic function, lack specificity for a particular disorder. Recently, a CVR pattern particular to chronic fatigue syndrome has been observed. In the present study, we aimed to develop methodologies for assessing disease-specific CVR patterns. As a prototype, a population of 50 consecutive patients with FMF (familial Mediterranean fever) was studied and compared with control populations. A 10 min supine/30 min head-up tilt test with recording of the heart rate and blood pressure or the pulse transit time was performed. Five studies were conducted applying different methods. In each study, statistical analysis identified independent predictors of CVR in FMF. Based on regression coefficients of these predictors, a linear DS (discriminant score) was computed for every subject. Each study established an equation to assess CVR, calculate DS for FMF and determine the sensitivity and specificity of the DS cut-off. In each of the five studies, abnormal CVR was observed in FMF patients. The best accuracy (88% sensitivity and 90.1% specificity for FMF) was obtained by a method based on beat-to-beat heart rate and pulse transit time recordings. Data was processed by fractal and recurrence quantitative analysis with recordings in FMF patients compared with a mixed control population. Identification of disease-specific CVR patterns was possible with the methodologies described in the present study. In FMF, disease-specific CVR may be explained by the interplay between neuroendocrine loops specific to FMF with cardiovascular homoeostatic mechanisms. Recognition of disease-specific CVR patterns may advance the understanding of homoeostatic mechanisms and have implications in clinical practice.

Adult↗

Cardiovascular reactivity in fibromyalgia: evidence for pathogenic heterogeneity.

OBJECTIVE: To evaluate disease-specific cardiovascular reactivity patterns in patients with fibromyalgia (FM) using a recently described method called fractal and recurrence analysis score (FRAS). METHODS: The study group included 30 women with FM, average age 46.7 years (SD 7.03). An age matched group of 30 women with other rheumatic disorders or having a dysautonomic background [chronic fatigue syndrome (CFS), non-CFS fatigue, neurally mediated syncope, and psoriatic arthritis (PsA)] served as controls. Subjects were evaluated with a head-up tilt test with beat-to-beat recording of the heart rate (HR) and pulse transit time. A 10-minute supine phase was followed by 600 cardiac cycles recorded on tilt. Data were processed by recurrence plot and fractal analysis. Variables acting as independent predictors of the cardiovascular reactivity were identified in FM patients versus controls. RESULTS: No statistically significant differences were found between the groups by univariate analysis comparing 92 variables of cardiovascular reactivity in FM patients compared to controls. CONCLUSION: Study of cardiovascular reactivity utilizing a head-up tilt test and processing the data using the FRAS method did not reveal a specific FM-associated abnormality. Our data confirm studies that utilized other methodologies and reached similar conclusions. Patients with FM represent a heterogenous group with respect to their pattern of cardiovascular reactivity.

Arthritis, Psoriatic↗

Pulse transit time by R-wave-gated infrared photoplethysmography: review of the literature and personal experience.

OBJECTIVE: Pulse transit time (PTT) is the time it takes a pulse wave to travel between two arterial sites. A rela tively short PTT is observed with high blood pressure (BP), aging, arteriosclerosis and diabetes mellitus. Most methods used for measuring the PTT are cumbersome and expensive. In contrast, the interval between the peak of the R-wave on the electrocardiogram and the onset of the corresponding pulse in the finger pad measured by photoplethysmography can be easily measured. We review herein the literature and impart the experience at our institution on clinical applications of R-wave-gated photo-plethysmography (RWPP) as measurement of PTT. METHODS: The MEDLINE data base on clinical applications of RWPP was reviewed. In addition, studies performed in the author's institution are presented. RESULTS: When used as a surrogate for beat-to-beat BP monitoring, RWPP did not meet the level of accuracy required for medical practice (two studies). RWPP produced accurate and reproducible signals when utilized as a surrogate for intra-thoracic pressure changes in obstructive sleep apnea, as well as BP arousals which accompany central sleep apnea (five studies). In estimation of arterial stiffness, RWPP was unsatisfactory (one study). In assessment of cardiovascular reactivity, abnormal values of RWPP were noted in autonomic failure (one study), while disease-specific reactivity patterns were identified utilizing a method involving RWPP (two studies). CONCLUSIONS: In clinical practice, sleep-apnea may be accurately monitored by RWPP. RWPP seems to reflect autonomic influences and may be particularly well-suited for the study of vascular reactivity. Thus, further descriptions of disease-specific cardiovascular reactivity patterns may be possible with techniques based on RWPP. Other clinical uses of RWPP are investigational.

Blood Pressure↗

The case for hepatitis C arthritis.

OBJECTIVE: To present the data available supporting the existence of an arthropathy associated with hepatitis C infection. METHODS: The MEDLINE database was searched for "arthritis" intersecting with "hepatitis C" in addition to the authors' investigations and experience on this subject. RESULTS: Arthritis, not otherwise explained, has been noted in 2% to 20% of hepatitis C virus (HCV) patients. This arthritis is rheumatoid-like in two thirds of the cases and a waxing/waning oligoarthritis in the rest. Cryoglobulinemia alone does not explain the arthritis, and there is difficulty in differentiating it from rheumatoid arthritis. The arthropathy is nonerosive/nondeforming. Whereas nonsteroidal anti-inflammatory drugs, low-dose corticosteroids, and hydroxychloroquine may be helpful, conventional treatment of arthritis may be problematic in the context of viral hepatitic arthropathy. Antiviral therapy is most effective, even without viral clearance, but rheumatic complications may ensue. CONCLUSIONS: HCV arthropathy should be considered in the differential diagnosis of new-onset arthritis.

Algorithms↗

Dysautonomia in chronic fatigue syndrome: facts, hypotheses, implications.

The diagnosis of chronic fatigue syndrome (CFS) is based on patient history and treatment on cognitive behavior therapy and graded exercise. There is increasing evidence that dysautonomia occurs in CFS manifest primarily as disordered regulation of cardiovascular responses to stress. We impart our experience relating to diagnosis, monitoring, and treatment of CFS based on identification and management of dysautonomia. Recently proposed methods for assessment of the cardiovascular reactivity, the 'hemodynamic instability score' (HIS) and the 'Fractal and Recurrence Analysis-based Score' (FRAS), served for this purpose. On HUTT, a particular dysautonomia is revealed in CFS patients that differ from dysautonomia in several other disorders. This distinct abnormality in CFS can be identified by HIS >-0.98 (sensitivity 84.5% and specificity 85.1%) and FRAS > +0.22 (sensitivity 70% and specificity 88%). Therefore, the HIS and FRAS may be used, in the appropriate clinical context, to support the diagnosis of CFS, which until now, could only be subjectively inferred. A pilot study suggested that midodrine treatment, directed at the autonomic nervous system in CFS, results first in correction of dysautonomia followed by improvement of fatigue. This finding implies that dysautonomia is pivotal in the pathophysiology CFS, at least in a large part of the patients, and that manipulating the autonomic nervous system may be effective in the treatment of CFS.

Arrhythmias, Cardiac↗