Tomas S. Bocanegra

Articular involvement in human Brucellosis: A retrospective analysis of 304 cases

Brucellosis is a zoonosis which in humans is caused by one of four species of the Brucella genus: B. melitensis, B. abortus, B. suis and B. canis. B. abortus is the species prevalent in North America and Europe and B. melitensis in most developing countries. Differences in disease manifestations may be accounted for either by differences in the species or by differences in the host. Articular involvement in brucellosis, although recognized since 1904, has been variably emphasized. Three hundred and four cases of human Brucellosis caused by B. melitensis, the prevalent species in Perú, were seen during a 12-yr period in one Lima hospital. Fever, malaise and hepatomegaly were the most frequent findings. Diagnosis was greatly improved when cultures were done in the biphasic Ruiz-Castañeda medium, rather than in trypticase soy broth. Serologic diagnosis is still important, and it should include standard tube testing, detection of IgG blocking antibodies and fractionation with 2-ME in chronic cases. The disease may take one of three courses: acute, (< 8 wk), chronic (> 8 wk) or undulant (periods of remissions and exacerbations). Four syndromes were recognized in a total of 33.8% of patients with Brucellosis. The most frequent pattern (in approximately 46.6% of patients with arthritis) was sacroiliitis, usually non-destructive and either uni- or bilateral. The second most frequent articular syndrome was peripheral arthritis (38.8%), manifested either as a single large lower extremity joint or as an asymmetric pauciarthritis. Rarely patients presented with a rheumatoid-like arthritis. Mixed arthritis (7.8%) was a combination of the first two. The above forms occurred in patients with an acute or undulant course. Spondylitis was the least common form of arthritis (6.8%), and differed significantly from the other forms of arthritis in the duration of symptoms (chronic course), age of patients (older individuals) and the paucity of fever and malaise. It also tended to be destructive. The arthritis usually resolved with the combined regimen of tetracycline (2 g p.o. for 21 days) and streptomycin (1 g i.m. for 21 days) without sequelae. Illustrative cases of these syndromes are presented. The relatively benign nature of most of the patients with bruccellar arthritis lead us to postulate that they are for the most part reactive arthritides. Host factors are thought to be important in determining the response to the infection, but they are yet to be identified. Our own genetic studies have failed to identify an increased frequency of B27 or CREG antigens in the patients with sacroiliitis.(ABSTRACT TRUNCATED AT 400 WORDS)

Clinical findings in symptomatic women with silicone breast implants

We report the clinical findings in a series of women with silicone breast implants (SBI) and rheumatic disease. These findings represent the first 50 patients seen at the University of South Florida Medical Clinic between March 1977 and January 1991. The average age was 44 years with a range of 30 to 66 years. The most common clinical findings included chronic fatigue, muscle pain, joint pain, joint swelling, and lymphadenopathy. Seventeen women with an average Steinbrocker functional class of 1.8 decided not to remove the implants. An average of 14 months later, follow-up showed no change in their condition. Thirty-three women, with an average functional class of 2.5 underwent implant removal. Twelve of the 33 had documented implant rupture. During an average follow-up of 22 months after implant removal, 24 women improved clinically, 8 did not change, and 1 worsened. We believe this series supports a relationship between silicone breast implants and rheumatic disease signs and symptoms. Although this report is not a definitive epidemiological study, findings suggest that physicians should inform women about the possible benefit of implant removal.

Reactive arthritis induced by parasitic infestation.

Arthritis developed in two patients during the course of parasite infestation with Strongyloides stercoralis and Taenia saginata, respectively. The joint involvement was polyarticular and symmetrical but seronegative and nonerosive radiologically. We found evidence of abnormal humoral immunity to the parasites, immune complexes in serum and synovial fluid, and immunoglobulin deposits in the synovia. Nonsteroidal anti-inflammatory agents proved ineffective but specific antiparasitic treatment resulted in resolution of the symptoms and immunologic abnormalities. Our findings provide further documentation of the interaction between the bodys immune system and parasites and suggest that arthritis induced by parasitic infestation may be mediated by immune complex formation in susceptible hosts.

Circulating immune complexes in the seronegative spondyloarthropathies

Abstract Circulating immune complexes (CIC) were determined in a large population of patients with seronegative spondyloarthropathies. In addition, we attempted to correlate the presence and levels of CIC with other parameters of disease activity in a serial fashion. CIC were measured using the Raji cell assay and the solid-phase Clq assay. A total of 92 patients were studied. These included 30 with ankylosing spondylitis (AS), 30 with psoriatic arthritis (PsA), 20 with Reiters syndrome, and 12 patients with Crohns arthritis (CA). Elevated levels of CIC were found in 73.3% (22 of 30) of AS patients, 60% (18 of 30) of PsA patients, 80% (16 of 20) of Reiters patients, and 67% (8 of 12) of Crohns patients studied. Both assays yielded concordant results. There was a significant correlation with disease activity, in particular arthritis, and the levels and incidence of CIC markedly declined in all groups when disease activity was under better control. Density gradient analysis of several sera revealed immune complex reactive material mainly in the 19 S region. This study suggests that CIC may play a role in the pathogenesis of some of the clinical manifestation of these conditions.

Immune complex-mediated renal involvement in relapsing polychondritis

A patient with relapsing polychondritis who presented with rapidly progressive glomerulonephritis is described. This is the fourth case in which this association is reported. Crescentic glomerulonephritis was found on renal biopsy. Evidence for immunologic participation in the pathogenesis of this condition is suggested by the demonstration of circulating immune complexes, immunoglobulin and complement deposition by immunofluorescence, and electron dense deposits by electron microscopy of the kidney. Favorable response followed therapy with prednisone and dapsone.

Factors Influencing Post‐Menopausal African‐American Women's Participation in a Clinical Trial

The Office on Women’s Health Research was established within the Office of the Director, National Institutes of Health (NIH) in 1990 with a mandate to strengthen and enhance prevention, diagnosis, and treatment of illness in women and to enhance research related to diseases and conditions that affect women. The NIH Office for Women’s Health Research summary of public testimony targeted the following areas as high priority for research: cancer prevention (especially breast cancer) cardiovascular disease, osteoporosis, autoimmune diseases, sexually transmitted diseases, work site safety, domestic violence, postnatal care, AIDS, and consequences of women’s hormonal cycles for pharmacotherapy (Barry, Gooding, Harris, Hazzard, 8c Winograd, 1993). The diversity of women’s health needs was stressed, considering special populations, African-American, Hispanic, and poor women (Grisso & Watkins, 1992). In keeping with the priorities of the NIH Office for Women’s Health Research, the authors implemented an observational study to identify risk factors in AfricanAmerican post-menopausal women and to further identify women who would be eligible for a clinical trial examining the effects of alendronate on bone density. (The geminal biphosphonates are specific inhibitors of bone resorption, potentially useful in osteoporosis.) This report describes efforts undertaken to recruit subjects from the community of African-American women for an observational study and a subsequent clinical trial. The observational study was designed to identify health risk factors in this group about which very little is known, and to screen subjects for eligibility for the clinical trial. According to the National Institute on Aging (NIA), half of all people older than 75 suffer from osteoporosis, a major cause of fractures in the spine, hip, wrist, and other bones. Twenty-five percent of women older than 60 have osteoporosis (Barry et al., 1993). The prevalence of osteoporosis in African-American women is not known, but is expected to be a great deal lower than in whites. Clinicians report that African-American women who do experience a fracture of the femur have a much longer recovery time and a higher rate of mortality than whites (Bocanegra, personal communication, January 13, 1994). Women’s health has been the missing chapter in America’s focus on medical research. Heart disease, cancer, and osteoporosis are the three main causes of morbidity and mortality in older women. While a major focus has been launched in these areas during the last 3 years, few efforts have been directed specifically at older African-American women (Cotton, 1992). In the past 5 years, the NIH has launched major campaigns and guidelines to encourage the recruitment of minorities and women in clinical trials. Critical to the success of any clinical trial is the recruitment of adequate sample sizes of eligible subjects and the prevention of subject attrition once the trial begins (Bennett, 1993). The purpose of this substudy was to determine which factors most influence post-menopausal African-American women’s participation in a multisite clinical trial. Research questions for the substudy were: Which recruitment methods work best with African-American women? 0 Which methods prevent attrition and adherence to the study protocol? 0 What special strategies need to be considered in recruiting and implementing a clinical trial for this population of women?

In vitro cytotoxicity of human endothelial cells in polymyalgia rheumatica and giant cell arteritis

SummaryWe studied sera from 20 patients with polymyalgia rheumatica (PMR)/giant cell arteritis (GCA), 15 patients with systemic lupus erythematosus (SLE), 15 patients with the CREST syndrome (calcinosis, Raynauds phenomenon, esophageal dysfunction, sclerodactyly, and telangectasia) and 33 age and sex matched controls for cytotoxicity against human endothelial cells using a 51Cr release assay. We observed increased levels of endothelial cytotoxic activity in the PMR/GCA sera compared with controls (P<0.001). This cytotoxicity was predominantly found in the GCA group, where 7 out of 10 patients (70%) demonstrated significant cytotoxicity. Sequential studies showed that the cytotoxic activity returned to normal when the disease was under control. Although 7 SLE and 3 CREST sera had significant cytotoxic activity, as a group they did not differ from controls (P<0.05). Pre-incubation with soybean trypsin inhibitor suppressed the cytotoxic activity in the positive sera suggesting the cytotoxicity is mediated via a protease mechanism.Our results demonstrate the presence of a cytotoxic factor in the serum of patients with PMR/GCA which may play an important role in the pathogenesis of the vascular lesions observed in these disorders.