PubMed Health⌕ Search

Biomedical subjects

G Slobodin

Publications and source records attributed to G Slobodin.

18 recordsLinked to original sources
PubMed2006

Changes in macrophage function after rituximab treatment in patients with rheumatoid arthritis.

OBJECTIVE: To assess changes in macrophage phenotype and function after rituximab-induced B cell depletion in patients with rheumatoid arthritis (RA). METHODS: 10 patients with RA were treated with rituximab, achieving significant B cell depletion 4 months later. Clinical improvement, rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP) antibodies, mRNA of B cell activating factor (BAFF), interleukin (IL) 10 and CD86 in human monocyte-derived macrophages (HMDMs) and tumour necrosis factor alpha (TNFalpha) secretion from cultured HMDMs were assessed at baseline and after the depletion. RESULTS: A clinical response of American College of Rheumatology (ACR) 50% improvement was noted in six patients, and another two patients responded with moderate improvement, equivalent to ACR 20-50% improvements. RF and anti-CCP antibodies were positive at baseline in seven of ten patients. RF disappeared or declined in six patients 4 months after treatment, correlating with clinical improvement. By contrast, anti-CCP remained unchanged in six patients. After rituximab treatment, and in association with clinical improvement, BAFF, IL10 and CD86 mRNA expression in HMDM were significantly upregulated compared with values at baseline. A significant decrease in TNFalpha in the supernatant of cultured HMDM was also noted. CONCLUSIONS: In addition to B cell depletion and attenuation in some of the specific autoantibodies, clinical improvement in rituximab-treated patients with RA occurred in association with changes in macrophage function.

Aged↗
PubMed2006

Nonspecific dizziness: frequency of supine hypertension associated with hypotensive reactions on head-up tilt.

The clinical syndrome of supine hypertension associated with orthostatic hypotension (OH) in given individuals is recognized by specialists, but is underdiagnosed in the community. The objective of this study was to assess supine hypertension associated with hypotensive reactions on head-up tilt (SH-HRT) among patients evaluated for nonspecific dizziness. Consecutive patients with nonspecific dizziness were studied with a 10-min supine 30-min head-up tilt test. Supine hypertension (SH) was diagnosed when supine systolic blood pressure (SBP) was > or = 140 mmHg and/or supine diastolic blood pressure (DBP) was > or = 90 mmHg. Hypotensive reactions on tilt (HRT) were diagnosed when SBP decreased by > or = 30 mmHg on tilt and/or DBP decreased by > or = 15 mmHg. Of 430 patients tested, 42 (9.8%) had SH-HRT. The median age was 67 years; 37 had a pretest diagnosis of hypertension, with treatment. The median supine BP was 162/90 mmHg; the median nadir BP on tilt was 118/78 mmHg. Four SH-HRT patterns were recognized: (I) SH with typical neurogenic OH (n = 6), (II) SH with vasovagal reaction on tilt (n = 4), (III) SH with sustained HRT (n = 28), and (IV) SH with mixed orthostatic-vasovagal reaction on tilt (n = 4). Dizziness on tilt occurred in 25% of patients category III (SH with sustained HRT), while appearing universally in other SH-HRT patterns. In conclusion, nonspecific dizziness may be the chief complaint in patients with SH-HRT, a disorder often unrecognized by clinicians. Different patterns of SH-HRT on HUTT may reflect different aberrations in cardiovascular homeostasis and may require differentiated management strategies.

Aged↗
PubMed2006

The emergency room in systemic rheumatic diseases.

Complications of systemic rheumatic diseases frequently have protean manifestations and may present a diagnostic problem. Patients with connective tissue diseases and vasculitides may have dangerous or life threatening conditions, which must be recognised and treated promptly to prevent rapidly evolving morbidity and mortality. Knowledge of possible emergencies in the context of a defined rheumatic disease may aid in promoting a high index of suspicion and contribute significantly to the timely diagnosis of many potentially dangerous conditions. This review is written for the emergency room physician and discusses the early recognition of selected emergencies in the context of a defined rheumatic disease.

Antiphospholipid Syndrome↗
PubMed2006

The patient with supine hypertension and orthostatic hypotension: a clinical dilemma.

Coexistent supine hypertension and orthostatic hypotension (SH-OH) pose a particular therapeutic dilemma, as treatment of one aspect of the condition may worsen the other. Studies of SH-OH are to be found by and large on patients with autonomic nervous disorders as well as patients with chronic arterial hypertension. In medical practice, however, the aetiologies and clinical presentation of the syndrome seem to be more varied. In the most typical cases the diagnosis is straightforward and the responsible mechanism evident. In those patients with mild or non-specific symptoms, the diagnosis is more demanding and the investigation may benefit from results of the tilt test, bedside autonomic tests as well as haemodynamic assessment. Discrete patterns of SH-OH may be recognisable. This review focuses on the management of the patient with coexistent SH-OH.

Aged↗
PubMed2005

Statin escape phenomenon: Does it really exist?

BACKGROUND: The normalization of blood lipid profile has become an accepted method of primary and secondary prevention of vascular disease, with statins being the most popular group of medicines prescribed to lower cholesterol and LDL cholesterol levels. The failure of statins, administered in an appropriate dose, to maintain the optimal level of LDL cholesterol is a rare phenomenon, and is still not well understood in patients compliant for both medication and diet. The entity of "statin escape phenomenon", proposed to explain the failure of statins in some of these patients, has not been studied or characterized extensively, and reports of its prevalence are scarce. METHODS: Patients with hyperlipidemia type 2a or 2b who had been treated with statins for at least 1 year and who were followed up in the lipid clinic on a regular basis every 3-4 months were included in this study. The charts of patients whose LDL cholesterol levels were elevated by 15% or more while receiving the same treatment were analyzed, and patients with putative statin escape phenomenon were included in the study and further characterized. RESULTS: Forty-five of 358 statin-treated patients demonstrated a 15% increase in LDL cholesterol levels, leading to suspicion of statin escape phenomenon. However, a strict exclusion analysis left only two patients without evident potential triggers for the observed elevation in LDL cholesterol. CONCLUSIONS: Whether a statin escape phenomenon really exists is still not certain, but if it does exist, it is probably an uncommon event with a low prevalence.

Journal Article↗
PubMed2005

Hyperventilation and amplified blood pressure response: is there a link?

Based on prior studies, the hypothesis that hyperventilation (HV) may have a pressor effect and play a causal role in hypertension has been suggested. The objective of this study was to correlate HV with blood pressure (BP)-change during a postural challenge. Consecutive subjects referred for evaluation of syncope, dizziness, chronic fatigue syndrome (CFS), fibromyalgia, or non-CFS fatigue were assessed with a 10-min supine 30-min head-up tilt test combined with capnography. We selected for analysis the records of patients aged 17-70 years, not taking vasoactive medications, having sitting systolic BP (SBP) < 140 mmHg, sitting diastolic BP (DBP) < 90 mmHg, and who completed 30 min of tilt. HV was diagnosed when end-tidal pressure of CO2 < 30 mmHg was recorded consecutively for > or = 10 min. Postural hypertension (PHT) was diagnosed when DBP on tilt > or = 90 mmHg was recorded consecutively for > or = 10 min. DBP-change was computed as (median DBP on tilt) -(median DBP supine). PHT and DBP-change were correlated with HV. A total of 320 patient charts were reviewed. PHT was present in 30 cases. The mean DBP-change in patients with PHT was +9.9 mmHg (s.d. 5.8), with three patients manifesting HV. Of the remaining 290 patients, 56 had HV, their mean DBP-change was -0.3 mmHg (s.d. 7.2). The other 234 patients without HV had a mean DBP-change +0.95 mmHg (s.d. 5.7), comparable to the DBP-change in patients with HV. In, conclusion, posturally induced HV was not associated with an increase in BP, nor was PHT associated with HV, except in a small minority of cases.

Adolescent↗
PubMed2002

Peripheral B-cell CD5 expansion and CD81 overexpression and their association with disease severity and autoimmune markers in chronic hepatitis C virus infection.

Hepatitis C virus (HCV) infection is associated with immune-mediated abnormalities and B-cell lymphoproliferation evolving to an overt lymphoma. Recently, CD81 was identified as an HCV receptor on B-lymphocytes, providing a mechanism by which B cells are infected and activated by the virus. In addition, expansion of CD5+ B lymphocytes was described to be associated with various non-HCV related autoimmune disorders. Therefore, we studied the possible role of peripheral B cells CD81 and CD5 over-expression in the development of HCV-related autoimmunity and their association with disease severity in chronic HCV infection. Peripheral B cells CD5 expression and mean fluorescence intensity (MFI) of CD81 were determined in 30 HCV-infected patients, 30 healthy controls and 15 patients with hepatitis B virus infection using fluorescence-activated cell scan (FACS). We have also investigated the association between peripheral CD5 and CD81 B-cell over-expression and markers of autoimmunity and disease severity in patients chronically infected by HCV. CD5+ B-cells were increased in chronic HCV infection (23.2 +/- 7.2%) compared with those of healthy controls (15 +/- 5.5%) (P < 0.0001) and chronic HBV infection (19 +/- 3.7%) (P = 0.08). CD81 MFI was significantly higher in HCV-infected compared to HBV-infected patients and healthy controls. Both increased CD81 MFI and CD5+ B-cell expansion were associated with the production of rheumatoid factor and mixed cryoglobulins and positively correlated with HCV viral load and histological activity index. The overexpression of CD81 and the expansion of CD5+ peripheral B-cells in HCV-infected patients may possibly play a role in the development of HCV-associated autoimmunity and lymphoproliferation.

Adult↗
PubMed2001

Enhanced peripheral T-cell apoptosis in chronic hepatitis C virus infection: association with liver disease severity.

BACKGROUND/AIMS: It has been suggested that enhanced T-cell apoptosis in hepatitis C virus (HCV) infection may lead to down-regulation of their cellular immune response, thus contributing to the persistency of HCV infection. In the present study we have investigated the role of bcl-2 and nuclear factor kappa B (NFkappaB) in dexamethasone-induced apoptosis of peripheral T cells in chronic HCV infection. METHODS: The expression of bcl-2 and NFkappaB in peripheral T cells as well as spontaneous and dexamethasone-induced T-cell apoptosis were studied in HCV-infected patients (n=21), hepatitis B virus (HBV)-infected patients (n=14) and healthy individuals (n=19). These parameters were correlated with markers of autoimmunity and disease severity. RESULTS: NFkappaB, but not bcl-2 expression, was significantly decreased in the HCV-infected patients. This decrease was associated with the presence of mixed cryoglobulins (MC) and rheumatoid factor and was positively correlated with alanine aminotransferase (ALT) levels and histological activity index (HAI). Both spontaneous and dexamethasone-induced T-cell apoptosis were enhanced in HCV-infected patients; however, only the latter was correlated with the presence of MC, ALT levels and HAI. CONCLUSIONS: We confirm previous reports that enhanced T-cell apoptosis in HCV infection may play an important role in disease severity. Decreased expression of NFkappaB is important in the development of peripheral T-cell apoptosis, thus contributing to viral persistence and autoimmunity in these patients.

Adult↗
PubMed2000

Heart diseases affecting the liver and liver diseases affecting the heart.

BACKGROUND: The association of cardiac and liver disorders has not been extensively outlined in the literature. METHODS: A survey of the MEDLINE database was performed to assess the current status of research regarding the association between cardiac and liver disorders. RESULTS: Combined cardiac and hepatic disorders occur in 3 different settings: heart diseases affecting the liver, liver diseases affecting the heart, and cardiac and hepatic disorders with joint etiology. The spectrum of heart diseases affecting the liver includes mild alterations of liver function tests in heart failure, cardiogenic ischemic hepatitis, congestive liver fibrosis, and cardiac cirrhosis. The liver diseases affecting the heart include complications of cirrhosis such as hepatopulmonary syndrome, portopulmonary hypertension, pericardial effusion, and cirrhotic cardiomyopathy as well as noncirrhotic cardiac disorders such as high-output failure caused by intrahepatic arteriovenous fistulae. Cardiac and hepatic disorders with joint etiology include infectious, metabolic, immune, vasculitic, and toxic disorders. We propose a practical approach to a diagnostic workup of combined cardiac and hepatic disorders based on recognizing the sequence of appearance of the cardiac and liver disease, presence of features of a multisystem disease, and presence of pathognomonic features. The evaluation of combined cardiac and hepatic disorders takes into consideration the expected benefit of treatment and the risks related to invasive procedures. Accordingly, investigations can be limited to ancillary tests for patients with congested liver and mild alterations of liver function tests, in cardiogenic ischemic hepatitis, patients with cardiac cirrhosis who are proposed for conservative treatment, and multisystem disease involving the heart and the liver. Conversely, comprehensive investigations are recommended when invasive therapeutic interventions are considered for the treatment of hepatopulmonary syndrome, portopulmonary hypertension, or arteriovenous fistulae. CONCLUSION: Classification of a patient to any of the 3 categories-heart diseases affecting the liver, liver diseases affecting the heart, and cardiac and hepatic disorders with joint etiology-permits the physician to narrow the span of the possible diagnoses and allows for a more simple workup.

Comorbidity↗
PubMed2000

Treatment of refractory, symptomatic, hepatitis C virus related mixed cryoglobulinemia with ribavirin and interferon-alpha.

OBJECTIVE: To assess the benefit of interferon-alpha/ribavirin combination therapy in hepatitis C virus (HCV) infected patients with symptomatic mixed cryoglobulinemia (MC) who failed to respond to treatment with interferon-alpha (IFN-alpha). METHODS: Nine patients (mean age 57 +/- 14 yrs) with type II symptomatic MC who failed to respond to IFN-alpha monotherapy were re-treated with combination treatment of IFN-alpha 3 times weekly and ribavirin 15 mg/kg daily for 6 months. Five of 9 patients had previously received additional treatment during IFN-alpha monotherapy. Clinical and laboratory evaluations (including cryocrit level) were performed weekly for the first month and monthly thereafter. RESULTS: Baseline mean alanine aminotransferase (ALT) and cryocrit levels were 119 +/- 97 IU/l and 7.9% +/- 10%, respectively. All patients were HCV-RNA positive and 5 had cirrhosis. At the end of therapy, mean ALT level was 84 +/- 79 IU/l (p = 0.02), while normal ALT levels were observed in 4 of 9 patients (44%). However, complete virological response was achieved in only 2 patients (22%). Cryoglobulin became undetectable within 6 weeks of therapy in 7 patients (78%) and decreased significantly in 2 others (p = 0.008). A substantial improvement in MC related symptoms (arthralgia/arthritis, proteinuria, skin vasculitis) was achieved in all patients within 10 weeks of combination therapy, although polyneuropathy related symptoms were relatively resistant to treatment. CONCLUSION: Symptomatic, refractory HCV related MC should be considered as an indication for combination therapy with IFN-alpha and ribavirin. Improvement in MC related symptoms can be achieved even without complete biochemical or virological response.

Adult↗
PubMed2000

[Marked creatine-phosphokinase elevation in myopathy after treatment with bezafibrate].

Bezafibrate is a fibric acid derivative which has been widely used in the past 15 years. Recent studies have elucidated much of its mechanism of action, which mainly results in reduction of VLDL and triglyceride levels and in elevation of HDL. The drug is relatively safe and its side-effects well known, mild, and reversible. The most severe side-effect is myositis, varying from mild flu-like symptoms to rhabdomyolysis, which is extremely rare. The underlying situations most frequently associated with bezafibrate-induced myositis are renal insufficiency and concomitant treatment with certain other drugs. We describe 2 women who developed severe myositis with bezafibrate treatment. 1, aged 43, who had moderate diabetes but no renal insufficiency, was treated with metformin and warfarin, which can interact with bezafibrate and affect its metabolism. The other, aged 54, had renal insufficiency and was on home peritoneal dialysis. Her bezafibrate dose had been increased because of very high triglyceride levels. The aim of the study is to call attention to this significant side-effect of benzafibrate and to ways of preventing it.

Adult↗
PubMedDate not supplied

Hepatitis C virus-related arthritis: characteristics and response to therapy with interferon alpha.

OBJECTIVE: To characterize hepatitis C virus (HCV)-related arthropathy and to evaluate the response to treatment with interferon-alpha (INF-alpha). METHODS: We studied 28 HCV-infected patients with arthritis. All patients underwent complete clinical, laboratory and radiological evaluation, including assessment and follow-up by a rheumatologist. Twenty-five patients were treated with INF-alpha for a median period of 12 months. RESULTS: All patients were HCV-RNA positive (genotype 1b in 65%). The mean duration of arthropathy-related symptoms prior to the diagnosis of HCV infection was 12 months. 19 patients (68%) had symmetric polyarthritis and 19 (68%) had morning stiffness > or = 60 min. None of the patients had erosive disease or subcutaneous nodules. 12 (43%) had detectable cryoglobulin (mean cryocrit: 3.6 +/- 3.5%), 17 (61%) had rheumatoid factor (RF) (median titer: 1:80), and only 15 (54%) had elevated ESR. 14 patients (50%) had > or = 4 ACR (American College of Rheumatology) criteria for the diagnosis of rheumatoid arthritis (RA), 9 of whom were mistakenly diagnosed and previously treated as RA patients. Only 3 patients had a satisfactory response to previous treatment with anti-inflammatory or disease modifying drugs. Complete or partial response of arthritis-related symptoms in INF-alpha treated patients was observed in 44% and 32%, respectively. Cryoglobulin became undetectable in 9 of 12 patients. However, a complete biochemical and virological end-of-treatment response was achieved in only 8 (36%) and 5 patients (20%), respectively. CONCLUSION: HCV arthropathy should be considered in the differential diagnosis of any patient with arthritis, even in the absence of liver disease. Treatment with interferon-alpha may lead to substantial clinical improvement of HCV-related arthritis even without a complete biochemical or virological response.

Adult↗
PubMedDate not supplied

Pseudopodagra: A presenting manifestation of infective endocarditis.

Podagra is a term used to describe acute monoarthritis of the first metatarsophalangeal (1st MTP) joint. The most common diagnoses of arthritis in this joint are: crystal-induced synovitis, septic arthritis, traumatic conditions and reactive arthritis. When etiologies other than gout are involved this is frequently referred to as pseudopodagra. We report the case of a patient who presented with pain and swelling of the 1st MTP The absence of intraarticular crystals and hyperuricemia encouraged further evaluation of the patient. A cardiac murmur was investigated by echocardiography, which revealed valvular vegetations and the diagnosis of infective endocarditis (IE) was established. This is the first reported case of a podagra-like presentation of IE. As in this case, the diagnosis of gout should rest on findings beyond the presence at 1st MTP arthritis, with evaluation of all extraarticular signs in order to rule out other possible diagnoses.

Acute Disease↗
PubMedDate not supplied

Aortic involvement in rheumatic diseases.

OBJECTIVE: To review the prevalence, mechanisms, presentations and clinical significance of aortic involvement in rheumatic inflammatory diseases. METHODS: The medical literature, available through a PUBMED search was reviewed and the relevant information was summarized. In addition, selected articles related to aortic involvement in rheumatic diseases were included in this review. RESULTS: Rheumatic disorders may be categorized by their propensity to involve the aorta: conditions with a prevalence of 10% and more (Takayasu's arteritis, temporal arteritis, long-standing ankylosing spondylitis, Cogan's syndrome and relapsing polychondritis), disorders with uncommon but well documented aortic involvement and rheumatic conditions with rare case reports of such involvement. Clinical presentation of aortic disease is dependent on the part of aorta involved and may manifest by aortic pain and/or other symptoms caused by aortic dilatation, narrowing or aneurysm. The histopathology of inflammatory aortitis is characterized by lymphoplasmacytic infiltration with or without giant cells or granulomas. On the other hand, non-inflammatory aortic damage in rheumatic diseases may include Marfan-like cystic disintegration of the aortic media as well as accelerated atherosclerosis. Awareness of rheumatic conditions with a high potential for clinically significant aortic involvement may promote referral of such patients for aortic imaging and sometimes surgery before fatal complications intervene. CONCLUSION: Early diagnosis of aortic involvement can be advanced by informed consideration of such a complication in a rheumatic patient.

Aorta↗