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Biomedical subjects

L H Calabrese

Publications and source records attributed to L H Calabrese.

At least 19 recordsLinked to original sources
PubMed2006

Hepatitis B virus (HBV) reactivation with immunosuppressive therapy in rheumatic diseases: assessment and preventive strategies.

Understanding of the natural history and basic biology of hepatitis B virus (HBV) has increased greatly in recent years. In view of this, the following are reviewed here: (a) recent advances in HBV biology pertinent to the rheumatic disease population; (b) the risks of HBV reactivation in patients with rheumatic disease undergoing immunosuppression; and (c) potential strategies to manage these risks.

Antirheumatic Agents↗
PubMed2004

Safety of antitumour necrosis factor (anti-TNF) therapy in patients with chronic viral infections: hepatitis C, hepatitis B, and HIV infection.

Tumour necrosis factor alpha (TNFalpha) is a pivotal cytokine in host defences with broad ranging effects on the innate and adaptive immune systems. Clinically, TNFalpha inhibitors have demonstrated remarkable efficacy in a wide range of autoimmune and inflammatory disorders but clearly at the cost of heightened susceptibility to a variety of infections in those treated with these agents. Most reports to date have described increased susceptibility to intracellular pathogens in patients with underlying chronic viral infections, but little in the way of adverse event reporting in these patients has occurred. While the reported experience to date is rather limited, TNFalpha inhibitors have displayed a reasonable safety profile in the setting of some chronic viral infections and in certain circumstances have demonstrated adjunctive activity in the treatment of these infections. Given the high prevalence of chronic viral infections in patients who are candidates for anti-TNF therapy and the potential for these agents in the treatment of chronic viral illness, additional studies are urgently needed to assess the risks and benefits of such therapy in these populations.

Antirheumatic Agents↗
PubMed2004

Branch retinal artery occlusions as the presenting feature of primary central nervous system vasculitis.

A 39-year-old woman presented with multiple branch retinal artery occlusions almost three years before developing a mass lesion containing calcium in the left frontal lobe. Brain biopsy revealed a small vessel vasculitis and ischemic necrosis of brain with dystrophic calcification. We believe this to be the first case of primary CNS vasculitis with branch retinal artery occlusions and brain calcification.

Adult↗
PubMed2004

Infection with the human immunodeficiency virus type 1 and vascular inflammatory disease.

Since the beginning of the HIV epidemic a wide variety of vascular inflammatory diseases have been described in HIV infected patients. In terms of the primary forms of systemic necrotizing vasculitis, there are no convincing data suggesting HIV infection increases the risk of development of any form of these diseases, but it is possible--though yet unproven--that HIV may lessen the chance of developing other forms (i.e. ANCA-associated disease and HBV-associated PAN). Secondary vasculitis resulting from unusual pathologic expressions of opportunistic infections has been reported and has important clinical significance. Finally, there does appear to be growing clinical, epidemiologic and pathologic evidence that several distinctive forms of vascular inflammatory disease occur in certain settings. These include aneurysmal disease of the large arteries of the brain occurring in children and a large vessel aneurysmal disease primarily affecting the aorta and its branches in young HIV-infected patients from sub-Saharan Africa. Further study of these disorders is necessary to identify specific epidemiologic features and pathogenesis.

HIV Infections↗
PubMed2001

Placebo-controlled trial of prednisone in advanced HIV-1 infection.

OBJECTIVE: To examine the safety and the immunologic and virologic consequences of corticosteroid use in HIV-1 infection. METHODS: A randomized, double-blinded, placebo-controlled trial of corticosteroid administration in 41 patients with advanced HIV-1 infection. Patients had a baseline median CD4 cell count of 131 x 10(6) cells/l at enrollment and 85% had a history of opportunistic infection. All but one of the patients had been taking stable antiretroviral regimen, including a protease inhibitor in 36, for a median duration of 158 days. Patients were randomized to 8 weeks of prednisone 0.5 mg/kg daily or placebo. RESULTS: No AIDS-defining events occurred; two patients in each group developed oral candidiasis, and two patients on prednisone developed mild herpes simplex flares. None who developed oral candidiasis or herpes simplex was receiving prophylaxis and each responded promptly to therapy. In the prednisone group, two patients developed hyperglycemia and one diabetic increased insulin requirements. CD4 cell counts and plasma HIV-1 RNA levels did not change, but plasma tumor necrosis factor alpha levels and CD38+ CD8+ cells decreased significantly in those taking prednisone. CONCLUSION: Short-term prednisone administration is well tolerated and reasonably safe in advanced HIV-1 disease and decreases immune activation without effects on HIV-1 RNA levels or CD4 cell counts. These results suggest that, in stable HIV-1 disease, these immune activation markers are more likely consequences of but not inducers of HIV-1 replication.

Acquired Immunodeficiency Syndrome↗
PubMed2001

A disease-specific activity index for Wegener's granulomatosis: modification of the Birmingham Vasculitis Activity Score. International Network for the Study of the Systemic Vasculitides (INSSYS).

OBJECTIVE: To refine and validate the Birmingham Vasculitis Activity Score (BVAS) as a disease-specific activity index for Wegener's granulomatosis (WG). METHODS: Sixteen members of the International Network for the Study of the Systemic Vasculitides (INSSYS) revised the BVAS, with 3 goals: to reduce the redundancy of some component items, to enhance its ability to capture important disease manifestations specific to WG, and to streamline the instrument for use in clinical research. We defined the items and weighted them empirically as either minor (e.g., nasal crusting = 1 point) or major (e.g., alveolar hemorrhage = 3 points). We then validated the new, disease-specific BVAS/WG in 2 simulation exercises and a clinical case series that involved 117 patients with WG. RESULTS: We removed 38 items from the original BVAS, revised 9 items, and added 7 new items. Correlations between the scores on the BVAS/WG and the physician's global assessment (PGA) of disease activity were high, even when patients in remission were excluded. In the clinical case series, Spearman's rank correlation coefficient between the BVAS/WG and the PGA was r = 0.81 (95% confidence interval 0.73-0.87). The interobserver reliability using intraclass (within-case) correlation coefficients in the 2 simulation exercises was r = 0.93 for the BVAS/WG and r = 0.88 for the PGA in the first and r = 0.91 for the BVAS/WG and r = 0.88 for the PGA in the second. There was no significant observer effect in the scoring of the BVAS/WG or the PGA. The discriminant validity of the BVAS/WG was good: r = 0.73 (95% confidence interval 0.43-0.83). CONCLUSION: The BVAS/WG is a valid, disease-specific activity index for WG. Tested in simulation exercises and in actual patients, the BVAS/WG correlates well with the PGA, is sensitive to change, and has good inter- and intraobserver reliability. The INSSYS will use the BVAS/WG to assess the primary outcome in a phase II/III trial of etanercept in WG.

Granulomatosis with Polyangiitis↗
PubMed2001

Vasculitis. A collection of pearls and myths.

Important strides have been made in unraveling the pathophysiologic characteristics of some individual forms of vasculitis, but vasculitides continue to pose enormous challenges for clinicians. Over time, numerous myths and an occasional pearl have arisen from the care of patients with these disorders. In this collection of pearls and myths, we have attempted to pool our knowledge about the clinical care of vasculitis patients.

Giant Cell Arteritis↗
PubMed2001

Changing patterns of morbidity and mortality in HIV disease.

In patients with HIV infection, highly active antiretroviral therapy is improving survival, but at the price of a variety of metabolic side effects. Patterns of morbidity and mortality are changing: the leading cause of death is now kidney or liver failure instead of opportunistic infections.

Anti-HIV Agents↗
PubMed1999

Thalidomide's tightly controlled "comeback".

Thalidomide has anti-inflammatory properties and shows promise for treating a variety of infectious and autoimmune diseases, but it must be used with strict precautions.

Autoimmune Diseases↗
PubMed1999

AIDS update 1999: viral reservoirs and immune-based therapies.

The advent of highly active antiretroviral therapy (HAART) has brought about a dramatic decline in opportunistic infections, hospitalizations, and mortality in AIDS patients. However, the recent discovery that HIV can lay dormant in quiescent T cells and other tissues even in the face of HAART therapy has dampened optimism for a cure for AIDS, though it suggests new avenues of research.

Acquired Immunodeficiency Syndrome↗
PubMed1999

A common-sense approach to chronic fatigue in primary care.

Since chronic fatigue is so common, long-lasting, and fraught with functional and emotional consequences, early intervention can limit overuse of health care resources and forestall disability. To help patients, we must intervene before chronicity is established or iatrogenic harm has occurred. Care that integrates medical and psychologic concepts, together with symptom management, can prevent significant secondary impairment in most cases.

Adjuvants, Immunologic↗
PubMed1999

Rheumatoid arthritis and primary care: the case for early diagnosis and treatment.

Rheumatoid arthritis is a chronic inflammatory disease that can cause severe pain and disability. Disease management historically was based on a "therapeutic pyramid" in which treatment escalated as symptoms worsened. However, the demonstration of early joint damage in patients with rheumatoid arthritis has emphasized the importance of early identification and treatment. Key features in establishing a diagnosis include joint examinations, assessments of extra-articular manifestations, laboratory tests, and radiologic examinations. Care must be taken to rule out other disorders with symptoms that overlap those of rheumatoid arthritis. Treatment of rheumatoid arthritis typically involves disease-modifying antirheumatic drugs, nonsteroidal anti-inflammatory drugs, and low-dose corticosteroids--often used in combination. A new class of therapeutic agents designed to neutralize inflammatory cytokines has added a new dimension to the therapeutic armamentarium against rheumatoid arthritis. Etanercept, a bioengineered soluble receptor fusion protein that blocks tumor necrosis factor activity, is the first compound in this class to be approved for treatment of patients with refractory rheumatoid arthritis. Therapeutic trials indicate that etanercept can reduce disease activity with relatively few drug-related adverse effects, thus helping persons with rheumatoid arthritis return to more normal, healthy lives.

Adult↗
PubMed1999

Progression of autoimmune thyroiditis in an HIV-infected woman on HAART.

Changes in immunoregulation, among other factors, may initiate or exacerbate autoimmune thyroiditis. Strikingly high titers of antithyroid peroxidase antibodies have been found in HIV-infected patients, and, according to some studies, these increase further as HIV disease progresses. The pathogenesis of autoimmune thyroiditis is not totally understood, but activated CD4+ cells predominate in the infiltrate and are believed to be central to the process. Some investigators have postulated that endocrinologic autoimmunity might result from incomplete or unbalanced immune restoration with highly active antiretroviral therapy (HAART). The case presented here suggests progression from euthyroid Hashimoto's thyroiditis to hypothyroidism after initiation of HAART.

Adult↗
PubMed1998

T cell receptor peptide vaccination in rheumatoid arthritis: a placebo-controlled trial using a combination of Vbeta3, Vbeta14, and Vbeta17 peptides.

OBJECTIVE: Restricted T cell receptor (TCR) gene usage has been demonstrated in animal models of autoimmune disease and has resulted in the successful use of TCR peptide therapy in animal studies. This clinical trial was undertaken to determine the safety and efficacy of a combination of Vbeta3, Vbeta14, and Vbeta17 TCR peptides in Freund's incomplete adjuvant (IFA) in patients with rheumatoid arthritis (RA). METHODS: A double-blind, placebo-controlled, multicenter, phase II clinical trial was undertaken using IR501 therapeutic vaccine, which consists of a combination of 3 peptides derived from TCRs (Vbeta3, Vbeta14, and Vbeta17) in IFA. A total of 99 patients with active RA received either 90 microg (n = 31) or 300 microg (n = 35) of IR501 or IFA alone (n = 33) as a control. The study medication and placebo were administered as a single intramuscular injection (1 ml) at weeks 0, 4, 8, and 20. RESULTS: Treatment with IR501 was safe and well tolerated. None of the patients discontinued the trial because of treatment-related adverse events. Efficacy was measured according to the American College of Rheumatology 20% improvement criteria. Using these criteria, patients in both IR501 dosage groups showed improvement in disease activity. In the most conservative analysis used to evaluate efficacy, an intent-to-treat analysis including all patients who enrolled, the 90-microg dosage group showed a statistically significant improvement compared with control patients at the 20-week time point after the third injection. Trends toward improvement were shown in both the 90-microg and the 300-microg dosage groups at week 24 after the fourth injection. CONCLUSION: IR501 therapeutic vaccine therapy was safe and well tolerated, immunogenic, and demonstrated clinical improvement in RA patients. Additional clinical trials are planned to confirm and extend these observations.

Adult↗
PubMed1998

Infections and systemic vasculitis.

Bacterial infections can clinically mimic a primary vasculitic syndrome and can directly cause a vasculitis that may respond to prompt recognition and treatment of the infection. Increasing direct and indirect evidence is establishing links between certain infections and vasculopathies, including aortitis, atherosclerosis, and Wegener's granulomatosis. The literature on the hepatitis viruses, particularly hepatitis C, and various vasculitic syndromes continues to grow. The spectrum of clinical syndromes, including "essential" cryoglobulinemia (elicited by the hepatitis viruses) and HIV, continues to broaden. Clinical trials have begun to demonstrate the therapeutic value of antiviral therapy in patients with these conditions.

Bacterial Infections↗