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Biomedical subjects

R P Messner

Publications and source records attributed to R P Messner.

At least 19 recordsLinked to original sources
PubMed1992

Treatment of early Lyme disease.

PURPOSE: To compare the safety and efficacy of azithromycin, amoxicillin/probenecid, and doxycycline for the treatment of early Lyme disease, to identify risk factors for treatment failure, and to describe the serologic response in treated patients. PATIENTS AND METHODS: Fifty-five patients with erythema migrans and two patients with flu-like symptoms alone and fourfold changes in antibody titers to Borrelia burgdorferi were randomized to receive (1) oral azithromycin, 500 mg on the first day followed by 250 mg once a day for 4 days; (2) oral amoxicillin 500 mg and probenecid 500 mg, three times a day for each for 10 days; or (3) doxcycline, 100 mg twice a day for 10 days. If symptoms were still present at 10 days, treatment was extended with amoxicillin/probenecid or doxycycline for 10 more days. Evaluations were done at study entry and 10, 30, and 180 days later. RESULTS: Three of the patients who initially had symptoms suggestive of spread of the spirochete to the nervous system, one from each antibiotic treatment group, subsequently developed neurologic abnormalities, but symptoms in the other 54 patients resolved within 3 to 30 days after study entry. Six of the 19 patients (32%) (95% confidence interval, 13% to 57%) given amoxicillin/probenecid developed a drug eruption, whereas none of the patients given azithromycin or doxycycline had this complication. The presence of dysesthesias at study entry was the only risk factor significantly associated with treatment failure (p less than 0.001). By convalescence, 72% of the patients were seropositive, and 56% still had detectable IgM responses to the spirochete 6 months later. CONCLUSIONS: The three antibiotic regimens tested in this study were generally effective for the treatment of early Lyme disease, but the regimens differ in the frequency of side effects and in ease of administration.

Adult↗
PubMed1992

Anti-dsDNA antibodies in laboratory workers handling blood from patients with systemic lupus erythematosus.

The presence of antinuclear antibodies was determined in female laboratory workers with varying degrees of exposure to blood from patients with systemic lupus erythematosus (SLE). Subjects recruited from SLE research laboratories and a membership roster provided by the American Society for Medical Technology were classified according to self-reported frequency of handling blood from patients with SLE into high and low exposure groups. Employment and medical history were obtained by questionnaire from each study subject and their sera were tested for antibodies to double stranded DNA, single stranded DNA, and synthetic polynucleotide poly(dA-dC).poly(dG-dT) by ELISA. Analysis of the results using an independent t test showed the mean optical density for anti-dsDNA was higher in the high exposure group (mean = 0.010) than in the low exposure group (mean = 0.005, p = 0.016). There were no significant differences found between the 2 groups for anti-ssDNA or anti-poly(dA-dC).poly(dG-dT), but the means for both anti-dsDNA and anti-poly(dA-dC).poly(dG-dT) were higher in the laboratory workers than in an unexposed nonlaboratory group of women (p less than 0.001). Our results are provocative for they lend support to the hypothesis that a transmissible agent capable of causing autoantibody formation may exist in blood from patients with SLE.

Adult↗
PubMed1991

Differential inhibition of mitogenic responsiveness by monoclonal antibodies to beta 2-microglobulin.

A panel of 10 monoclonal antibodies (MoAbs) to human beta 2-microglobulin (beta 2m) was used to evaluate the modulation of lymphocyte activation induced by different mitogenic stimuli. All 10 MoAbs inhibited proliferative responses of peripheral blood mononuclear cells (PBMC) to phytohemagglutinin (PHA), concanavalin A (Con A), pokeweed mitogen (PWM), and allogeneic cells in mixed lymphocyte culture (MLC), although some MoAbs were inhibitory at much lower concentrations than others. No enhancement or direct mitogenicity was observed, but at low MoAb concentrations a delayed peak response sometimes occurred. Differentiation of B cells in PWM-stimulated PBMC cultures was also inhibited as measured by reduced accumulation of supernatant IgM and IgG. Anti-beta 2m MoAb did not interfere with the binding of PHA or PWM to PBMC, and membrane mobility as judged by subsequent capping of these lectins also appeared to be normal. Furthermore, anti-beta 2m was inhibitory when added 24 hr prior to peak responsiveness, and proliferative responses to the phorbol ester PMA in combination with ionomycin were also inhibited by MoAb, indicating that membrane-mediated events were not the target of inhibition. A comparison of the inhibitory effects of anti-beta 2m MoAb on activation by different stimuli revealed that PWM and MLC responses were much more sensitive to inhibition followed by, in order of decreasing inhibition, Con A, PHA, ionomycin alone, and PMA/ionomycin. A MoAb to a monomorphic determinant of HLA-A, B, C exhibited the same inhibitory trend, suggesting that the mechanism of inhibition was the same as for anti-beta 2m MoAbs. No inhibition was observed when PBMC were stimulated by PMA alone, suggesting that the MoAbs have little effect on activation mediated by protein kinase C but may preferentially affect the calcium-dependent pathway of activation. Thus, this differential inhibition observed with different stimuli may reflect the relative contribution of class I antigens to lymphocyte activation by a particular mitogen.

Antibodies, Monoclonal↗
PubMed1991

Arthritis due to tuberculosis, fungal infections, and parasites.

Tuberculous, fungal, and parasitic infections infect millions of people throughout the world. While other problems usually overshadow their rheumatologic manifestations, nearly all these infections can involve bone or joints and may on occasion present with rheumatologic symptoms. The classic model of these diseases presenting as chronic monoarticular arthritis is still generally valid but other presentations, such as tenosynovitis with atypical mycobacterial infections, erythema nodosum with leprosy, coccidioidomycosis and histoplasmosis, and reactive arthritis with schistosomiasis and helminthic infections, are now well established. The most dramatic change in the epidemiology of tuberculous infections in recent years is the increasing incidence in patients with the acquired immunodeficiency syndrome (AIDS). Mycobacterium avium complex infections in particular have increased dramatically and are a major problem in the later stages of AIDS. Reports of septic arthritis and tenosynovitis due to M. avium are likely to increase over the next few years.

Arthritis, Infectious↗
PubMed1991

Viral persistence during the developmental phase of Coxsackievirus B1-induced murine polymyositis.

Mice infected with coxsackievirus B1 (CVB1) develop a chronic hindquarter muscle weakness which resembles human polymyositis. In this study, we used in situ hybridization to screen for persistent viral RNA in hamstring and quadriceps muscles from mice that displayed various degrees of clinical weakness. At 28 to 31 days postinfection, when chronic myositis is well developed but infectious virus can no longer be recovered, persistent CVB1 RNA was found in hindquarter skeletal muscle of all 12 infected animals examined. Persistent CVB1 showed a multifocal distribution within muscle and was associated with three different histopathology patterns (HPPs). These three HPPs (HPP-1, HPP-2, and HPP-3) represent potentially different stages in the mechanism of persistence. They are based on the pattern of grains, the location of hybridization signal within the muscle, and the accompanying histopathology. In HPP-1, virus persisted in nonnecrotic muscle fibers and was not directly associated with foci of inflammatory cells. HPP-2 consisted of virus contained within necrotic myocytes that were surrounded by inflammatory cells. HPP-3 was rare and showed virus inside infiltrating mononuclear cells in a region where muscle tissue had been extensively destroyed. Persistent CVB1 occurred more frequently in severely diseased animals and in tissue sections displaying intense inflammation. Moreover, HPP-2 showed a stronger association with tissue inflammation and hindquarter weakness than did HPP-1. These data demonstrate that CVB1 persists in skeletal muscle for at least 28 to 31 days postinfection and support the concept that this persistence plays a role in the development of murine polymyositis.

Animals↗
PubMed1991

Mononuclear phagocyte system dysfunction in murine SLE: abnormal clearance kinetics precede clinical disease.

Although several studies have reported abnormal immune clearance in murine models of systemic lupus erythematosus (SLE), a consistent defect in mononuclear phagocyte function in SLE-prone mice has not been described. To evaluate the mechanism(s) of immune clearance in murine SLE, we applied the technique of kinetic analysis to clearance studies of radiolabeled, immunoglobulin-sensitized red blood cells in normal BALB/c and autoimmune BXSB, MRL-lpr/lpr, New Zealand black (NZB) and New Zealand black/white (NZB/W) mice. Clearance studies were performed in 4-week-old to 18-month-old mice with a complement-fixing rabbit IgG antimouse red blood cell antibody. Four clearance rate constants governing complement- and Fc-mediated clearance function were evaluated: complement-mediated sequestration (k1), C3b deactivation and release (k2), complement-dependent phagocytosis (k4), and Fc-mediated sequestration and phagocytosis (k3). BXSB male, MRL-lpr/lpr female and male, NZB female, and NZB/W female and male mice all had significantly decreased Fc-mediated clearance function (k3) when compared with control BALB/c mice (p less than 0.0001). This defect in Fc-mediated clearance was present in all four strains of autoimmune mice by 6 months of age and preceded the onset of serologic and clinical disease activity in NZB mice. Abnormal complement-mediated clearance was detected in MRL-lpr/lpr female and male mice, NZB female, and NZB/W female and male mice, but not in BXSB mice. In MRL-lpr/lpr mice decreased complement-mediated sequestration (k1, p less than 0.0001) and complement-dependent phagocytosis (k4, p less than 0.0001) were present as early as 4 weeks of age. In contrast, the change in complement-mediated clearance in NZB and NZB/W mice was characterized by decreased C3b deactivation and release (k2, p less than 0.001) and resulted in an enhanced early phase of clearance. Decreased k2 values in New Zealand mice occurred as early as 2 months of age, preceding serologic and clinical disease activity as well as decreased Fc receptor function. These studies demonstrated an early, progressive, and uniform defect in Fc-mediated clearance in the four murine strains of SLE studied. Complement-mediated clearance, however, varied considerably in lupus-prone mice, ranging from severe impairment in MRL-lpr/lpr to normal function in BXSB and accelerated clearance in NZB and NZB/W mice. Accelerated clearance in New Zealand mice was characterized by decreased C3b deactivation and release of antibody sensitized cells, which in turn led to increased phagocytosis of sensitized cells sequestered by complement-dependent processes.

Animals↗
PubMed1991

Difluoromethylornithine therapy of female NZB/W mice.

We studied the effects of difluoromethylornithine (DFMO), an experimental drug that inhibits the biosynthesis of natural polyamines, on anti-DNA antibody production, immunoglobulin synthesis, proteinuria, and blood urea nitrogen (BUN) in lupus-prone female NZB/W mice. Administration of 1% of the drug in drinking water reduced anti-DNA antibody levels by about 80% of that of untreated mice of the same strain. There was a reduction of IgG and IgA levels in older DFMO treated mice, whereas IgM level was not affected. Proteinuria and BUN were also significantly reduced in treated mice. Moreover, DFMO treatment reduced the concentration of putrescine and spermidine in spleen cells. Our results suggest that polyamine biosynthesis inhibition by DFMO may provide a new approach to the treatment of lupus.

Animals↗
PubMed1979

Sensitivity of lymphocytes to prostaglandin E2 increases in subjects over age 70.

We examined the sensitivity of lymphocytes from different age groups to inhibition by prostaglandin E2. Phytohemagglutinin-stimulated cultures of peripheral blood mononuclear cells from 12 healthy subjects over the age of 70 were much more sensitive to inhibition by exogenously added prostaglandin E2 than were cells from 17 young controls (ID50 congruent to 10 nM for the subjects over 70 vs. greater than 3 micronM for the young controls). The more senstivie lymphocytes from a subject over 70 were to prostaglandin E2, the lower was his or her response to phytohemagglutinin (r = 0.75, P less than 0.01). The mean responses to phytohemagglutinin of the peripheral blood mononuclear cells from the subjects over 70 were significantly depressed compared to the young controls. Addition of indomethacin, a prostaglandin synthetase inhibitor, to the cultures resulted in an increase in [3H]thymidine incorporation of 140 +/- 16% in the cells of the subjects over 70 vs. a 36 +/- 3% increase in the young controls (mean +/- SEM, P less than 0.001). The mean phytohemagglutinin response of the subjects over 70 was 40% of the control response without indomethacin. With addition of indomethacin the response of subjects over 70 rose to 72% of control. Thus, increased sinsitivity to prostaglandin E2 appears to be responsible in part for the depressed mitogen response of peripheral blood mononuclear cells from healthy subjects over 70.

Adult↗
PubMed1979

Suppressor cell function in sarcoidosis.

We investigated the role of suppressor cells in the depressed cellular immunity of patients with sarcoidosis. The mean response in 16 patients with active sarcoidosis to three concentrations of phytohemagglutinin was significantly (P less than 0.01) less than control values. Passage of the cells over glass wool resulted in a 116% increase in response to phytohemagglutinin in patients and a 39% decrease in control subjects. Addition of indomethacin to phytohemagglutinin cultures increased the response of cells in patients with sarcoidosis by 192% +/- 32% versus a 112% +/- 18%-increase for control subjects (mean +/- SEM, P less than 0.05). Patients had an increased percentage of monocytes in peripheral blood mononuclear cell preparations, and the percent monocytes correlated with the percent increase in phytohemagglutinin response after glass wool passage (r = 0.62, P less than 0.05). Thus, several factors contribute to the depressed phytohemagglutinin response in sarcoidosis patients: an increased suppression by the prostaglandin-producing suppressor cell, an increased percentage of monocytes, and an as yet undefined factor.

Adult↗
PubMed1978

Prostaglandin E inhibition of mitogen stimulation in patients with multiple sclerosis.

Kirbey et al have reported that leukocyte function from patients with multiple sclerosis is not suppressed by PGE2, as are normal leukocytes. We examined the ability of PGE2 (0.01-0.5 microgram/ml) to suppress Phytohemagglutinin induced 3H-thymidine incorporation in peripheral blood lymphocytes from multiple sclerosis patients and normals. There was no difference in sensitivity between the two groups. There was also no difference in activity of the prostaglandin producing suppressor cell between the multiple sclerosis patients and controls.

Humans↗
PubMed1978

Effect of indomethacin in vivo on humoral and cellular immunity in humans.

We studied the effect of indomethacin on intradermal skin testing and antibody responses in humans. Since we and others have shown that prostaglandins are suppressor cell mediators, it was probable that in vivo inhibition of prostaglandin synthesis might enhance the humoral and/or cellular immune response. Administration of indomethacin (Indocin) in a dosage of 100 mg/day to 15 normal men and women resulted in a significantly increased antibody titer to A-Victoria (P less than 0.025) as compared with age- and sex-matched controls. There was no difference in titer to A-New Jersey. Since 90% of the subjects had antibody titers to A-Victoria before inoculation, whereas none had detectable titers to A-New Jersey, we interpret this data as suggesting that indomethacin enhances the secondary but not the primary humoral immune response. Indomethacin administration did not alter the intradermal skin test responses.

Adult↗
PubMed1978

Prostaglandin suppression of mitogen-stimulated lymphocytes in vitro. Changes with mitogen dose and preincubation.

In this study we further characterize the properties of the prostaglandin-producing suppressor cell. Overnight preincubation of peripheral blood mononuclear cells results in an increased response of the cells to phytohemagglutinin or Concanavalin A compared to the response of fresh cells. This increase in mitogen response with preincubation was similar in magnitude to the increase in mitogen response of fresh cells after the addition of indomethacin. The two manipulations were not additive; that is, after preincubation, indomethacin caused much less enhancement of mitogen stimulation of peripheral blood mononuclear cells (100 +/- 12% increase before preincubation vs. 12 +/- 6% after preincubation; mean+/-SEM, P < 0.001). Preincubated cells also lose sensitivity to inhibition by exogenous prostaglandin E(2). It requires the addition of 100- to > 1,000-fold more exogenous PGE(2) to produce comparable inhibition of phytohemagglutinin-stimulated preincubated cells than is required for inhibition of phytohemagglutinin-stimulated fresh cells. The enhancing effect of indomethacin increases with decreasing doses of phytohemagglutinin. Indomethacin causes a 1,059+/-134% increase in [(3)H]thymidine incorporation at the lowest dose of phytohemagglutinin (0.2 mug/ml), and a 4+/-3% increase at the highest dose (20 mug/ml). This increase in response to indomethacin with a lower dose of phytohemagglutinin is due to increased sensitivity to inhibition by PGE(2) at lower mitogen doses. The prostaglandin-producing suppressor cell assay and the short-lived suppressor cell assay measure over-lapping phenomena. The increased suppressive effect of the prostaglandin-producing suppressor at suboptimal mitogen dose must be taken into account in the interpretation of any study where the response to a range of mitogen doses is studied.

Adult↗