Robert H. Persellin

Cervical fracture complicating ankylosing spondylitis: a report of eight cases and review of the literature.

Fracture of the cervical spine is a serious and often fatal complication of ankylosing spondylitis. An evaluation of eight patients and a review of 75 additional cases from the literature are presented. Although this complication is relatively uncommon, it is clear that people with advanced disease and complete ankylosis of the cervical spine are at increased risk of sustaining cervical fracture. When fracture occurs it usually stems from minor trauma resulting most commonly in disruption of the lower cervical segments (fifth through the seventh cervical vertebrae). Fracture is most likely the result of a hyperextension type injury, occurs through what was formerly an intervertebral space, and is unstable. Severe neurologic sequelae occur in 57 percent of the cases and the mortality rate (35 percent) is twice that observed with similar fracture involving normal spines. The majority of patients are best treated with closed reduction with halo traction together with body cast or jacket. Laminectomy is rarely indicted except in the event of an advancing neurologic deficit. With appropriate understanding and execution of management principles, the outcome in these patients can be favorable. Unfortunately, recognition of cervical fracture in patients with ankylosing spondylitis is often needlessly delayed. Distortion of normal anatomy in spondylitics, predominant fracture location in lower cervical spine segments and lack of obvious displacement make identification difficult. Thus, management is often inappropriate resulting in excessive neurologic injury and mortality.

Effect of pregnancy on immune complexes and rheumatoid factors in patients with rheumatoid arthritis

Rheumatoid arthritis is associated with circulating and intra-articular immune complexes and rheumatoid factors. The clinical activity of rheumatoid arthritis improves during pregnancy in the majority of women, with exacerbation following delivery. Concentrations of immune complexes, as detected by the Clq-binding assay, the Clq-solid phase assay, and the monoclonal rheumatoid factor-solid phase assay, decreased during gestation, with elevations following delivery. Concentrations of IgM-rheumatoid factor and IgG-rheumatoid factor, analyzed by radioimmunoassay, changed variably during pregnancy, increasing in some patients and decreasing in others. When examined serially before, during, and following pregnancy, changes in the concentration of circulating immune complexes and/or rheumatoid factors corresponded with the clinical changes in three patients. These observations document the significant effect of gestation on the concentration of circulating immune complexes in patients with rheumatoid arthritis. They also support the role of these laboratory tests in monitoring the clinical course of rheumatoid arthritis.

Review: Mechanisms of action of gold

Since the successful introduction of injectable gold compounds for the treatment of rheumatoid arthritis over 50 years ago, numerous studies on the possible mechanism of action have been performed. This heavy metal has been show to possess a bewildering array of biological effects. Studies using gold performed bothin vitro andin vitro can be grouped into anti-microbial, anti-immunologic, anti-inflammatory, anti-enzymatic and other effects. In this survey, we have analyzed these multiple approaches to the study of the mechanism of action of injectable gold preparations and apply the findings to rheumatoid arthritis.

Human polymorphonuclear leukocyte phagocytosis in pregnancy

The phagocytosis of S. aureus by normal human PMN leukocytes was inhibited by pregnancy serum. Control sera from normal adult nulliparous women, from men, and from cord blood all functioned normally in support of phagocytosis. However, particle ingestion was reduced significantly (p To determine at what stage in pregnancy the inhibition of phagocytosis could first be detected, sera were obtained from multiple pregnant donors and pooled according to week of gestation. Significantly fewer bacteria were ingested in each of the serum pools obtained after week 16 of pregnancy and the inhibitory effect persisted through gestation. Following delivery, less inhibition was detected as early as 2 days post partum. Phagocytosis assays were performed in six matched maternal and cord serum pairs. Five of the six maternal sera showed inhibition of phagocytosis; one pregnancy and all cord sera functioned normally in support of bacterial ingestion by normal granulocytes. Since neutrophils are essential to the development of rheumatoid arthritis and certain other inflammatory disorders, the subsidence of these diseases during gestation and their exacerbation post partum could be related, at least in part, to the inhibitory effects of pregnancy serum on leukocyte functions.

COEXISTENCE OF RHEUMATOID ARTHRITIS AND SYSTEMIC SCLEROSIS IN FOUR PATIENTS

The classic skin and internal organ system manifestations of systemic sclerosis developed in 4 individuals, each with an erosive, destructive chronic polyarthritis characteristic of rheumatoid arthritis. All had serum rheumatoid factors, anti-nuclear antibodies, hypergammaglobulinemia and circulating immune complexes. Each of the 4 has been resistant to treatment. The features of these patients, together with an analysis of this unusual coexistence of two connective tissue disorders, are presented.

Alteration of polymorphonuclear leukocyte surface charge by endogenous and exogenous chemotactic factors

We investigated the effects of chemotaxins on the surface charge of isolated human PMN. Chemotaxis was ascertained using Boyden chambers. Surface charge was calculated using data derived from cell mobility as measured in a cytophorometer. The electrophoretic mobility of cells exposed to all chemotactic agents studied was altered. Endotoxin-activated serum containing C5a, PMN lysosomal extracts from “resting” and from crystal-stimulated cells, and Gly-His-Gly, a synthetic tripeptide, all significantly reduced the net negative surface charge of isolated neutrophils. Only chemotactically active substances effected this change; controls including heat-inactivated serum, other subcellular fractions, and an inert tripeptide, Gly-Gly-Gly, did not alter cell mobility in an electric field. These findings are consistent with studies by others on the effects of chemotactic factors on cation fluxes and cell aggregation and suggest a possible mechanism by which PMN directional migration is regulated.

Induction of suppressor cell activity by human pregnancy serum.

ABSTRACT: Third trimester pregnancy serum caused a dose‐dependent inhibition of the one‐way allogeneic mixed leukocyte reaction (MLR) through an effect that occurred during the first 48 hours of culture. Pregnancy serum also inhibited the mitogenic responsiveness of normal mononuclear leukocytes to concanavalin A (Con A) while the responses to phytohemagglutinin (PHA) and pokeweed mitogen (PWM) were less affected. Preincubation of normal peripheral blood mononuclear cells (PBMC) for 48 hours with 10% pregnancy serum enhanced a suppressor activity transferable with cells. These pregnancy serum‐induced effector cells suppressed the MLR only when they were autologous to the responder population (p < 0.05). The same suppressor cell preparation inhibited the proliferative responses of autologous PBMC to Con A (p < 0.001) and PWM (p < 0.05). These data suggest that one or more factors in pregnancy serum can induce or enhance suppressor cell activity in vitro. A comparable increase in suppressor cell activity in vivo may be responsible for blocking maternal rejection of the fetus and for the observed improvement in clinical activity of rheumatoid arthritis during pregnancy.

The Detection of Circulating Immune Complexes and IgG and IgM Rheumatoid Factors in Normal Human Pregnancy

ABSTRACT: The development of immune complexes (IC) and rheumatoid factors (RF) during normal, uncomplicated pregnancy is a controversial issue. Discrepancies in previous reports are due most likely to the different methods used to detect both IC and RF. Using four sensitive radioimmunoassays for immune complexes employing both Clq and mRF and employing sensitive and specific radioimmunoassays for the detection of IgM‐RF and IgG‐RF, we examined the sera of 35 normal subjects in their third trimester of pregnancy. Immune complex concentrations as measured by four assays were not increased during gestation. However, both IgM‐RF and IgG‐RF were significantly elevated even though the concentrations of immunoglobulins M and G were virtually identical to the controls. These observations provide further insight into the immunological changes associated with pregnancy.

Leukocyte Sensitization against Synovial Components in Rheumatoid Arthritis: Blocking by Pregnancy Serum

The leukocyte adherence inhibition (LAI) test in arthritis can serve as an in vitro model for investigating cellular cooperation between mononuclear cells sensitized by cytophilic IgG rheumatoid factor(s) present in rheumatoid arthritis (RA) serum, normal synovial components, and polymorphonuclear cells. Since inflammatory and immunologic responses are altered during pregnancy, we studied the effect of pregnancy serum on the LAI. The adherence of normal leukocytes once sensitized in RA serum is inhibited by a synovial extract, but when these leukocytes are exposed to pregnancy serum prior to sensitization with RA serum, the cells are unresponsive to subsequent stimulation by the synovial extract (p less than 0.01). This blocking effect on sensitization is only present in serum obtained after the first trimester of pregnancy and can be detected even at serum dilutions of 1:100. Leukocytes obtained directly from pregnant subjects, washed, and then incubated with RA serum failed to react. Since pregnancy serum has been shown to mask certain cell membrane receptors, it is possible that our results are due to the blocking of IgG rheumatoid factor binding to mononuclear cells. This finding could contribute to the subsidence during pregnancy of some disorders such as rheumatoid arthritis.

Chemotaxis under agarose: Dependence upon polymorphonuclear leukocyte density

Since the number of polymorphonuclear leukocytes (PMN) responding to a chemotactic stimulus in the Boyden chamber is influenced by the cell density, we studied whether this variable was important in determining chemotaxis under agarose. The chemotactic index was determined by summing the product of each cell that had migrated from the chemotactic well by its distance and correcting this sum for random migration. Cell density (number of PMN per mm2 surface area of the agarose plate well) influenced the number of cells responding to the chemotactic stimulus. Only when more than 1.8 x 10(2) PMN/mm2 were used was chemotaxis then detected. For cell densities greater than this number, there was a highly positive correlation between cell density and chemotactic index (P less than 0.001). These findings are consistent with previous reports and indicate that PMN density is a critical variable when using the agarose method. In addition, these studies provide further evidence for cellular cooperation in the initial phases of the chemotactic response.