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OBJECTIVES: Complex regional pain syndrome type 1 (CRPS-1) can progress to joint stiffness, which may be related to pain and/or capsule-ligament contracture. In this context, it is difficult to distinguish the respective causative roles of pain and contractures. Nerve blocks (NBs) can be used to determine the aetiology of joint stiffness. Subsequent treatment will depend on whether contractures are present or not. The objective of the present study was to evaluate the diagnostic and therapeutic value of the nerve blocks in the management of joint stiffness caused by CRPS-1. DESIGN OF THE STUDY: A retrospective case series. METHODS: Implementation of NBs in subjects with joint stiffness caused by CRPS-1. Primary efficacy criterion: an increase in the range of joint movement. Secondary criteria: pain level, treatment decision, duration of therapeutic NBs, return to work. RESULTS: Fourteen patients with joint stiffness underwent 17 NBs. Ten NBs (59%) were associated with the normalization of the range of joint movement (i.e. the absence of contractures and the presence of an isolated pain component), prompting the implementation of physical therapy during NBs ("therapeutic NBs") in 90% of these cases. Three NBs (18%) were associated with a partial increase in the range of joint movement (i.e. a background of joint stiffness due to a combination of pain and contracture), prompting the implementation of a therapeutic NB in all of these cases. Four NBs (23%) were not associated with any increase in the range of joint movement (i.e. pure contractures), prompting consultation with a surgeon in all of these cases. Forty-three percent of the patients have since returned to work. CONCLUSIONS: Nerve block is a valuable diagnostic and therapeutic option in the management of joint stiffness caused by CRPS-1.

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Gangliosides on the external side of the plasma membrane are important modulators of cellular functions. In previous work we had found that in cultured human SK-N-MC neuroblastoma cells a cell surface sialidase activity specifically cleaved terminal sialic acids from gangliosides, leading to a shift from higher sialylated species to GM1 and a decrease of GM3. To further elucidate the function of the enzyme, we have now examined the consequences of ganglioside sialidase inhibition. When present in the culture medium, the ganglioside sialidase inhibitors 2-deoxy-2,3-dehydro-N-acetylneuraminic acid (NeuAc2en), heparin, and heparan sulfate caused dramatic changes in cell behavior. Thus, the inhibitors uniformly led to a complete release from contact inhibition of growth, and to the loss of the differentiation markers neuron-specific enolase and neurofilaments, and a decrease of cyclic AMP. In presence of NeuAc2en, cells that normally were spread out evenly and were firmly attached, appeared smaller, rounded, and only loosely adherent to the culture vessel. Exogenous addition of vibrio cholerae sialidase mimicked the action of the plasma membrane ganglioside sialidase by retarding cell proliferation and increasing intracellular acetylcholinesterase. That the ganglioside sialidase inhibitors in the culture medium indeed affected solely the cell surface enzyme and not also a lysosomal sialidase, was demonstrated in an experiment where the desialylation of exogenously added radioactive gangliosides was determined in absence and presence of NeuAc2en and NH4Cl, an inhibitor of lysosomal function. Taken together, our results suggest that the ganglioside sialidase on the surface of SK-N-MC cells is responsible for growth control and differentiation in this neuronal cell line.

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In cultured human neuroblastoma cells (SK-N-MC), a plasma membrane-bound besides a lysosomal ganglioside GM3 sialidase was detected. Both activities can be distinguished by the specific activation with detergents, as well as differential inhibition by Cu++. Plasma membrane and lysosomal sialidase specific activities showed strikingly different behaviour during the growth phase of neuroblastoma cells. Thus, the plasma membrane sialidase increased about 15-fold and mirrored cell growth, it differed from the kinetics of ornithine decarboxylase, an early marker of cell proliferation. The lysosomal sialidase, on the other hand, exhibited constant specific activities during growth of the cells, as did lysosomal and plasma membrane marker enzymes. When the sialidase inhibitor 2,3-dehydro-2-deoxy-N-acetylneuraminic acid was included in the culture medium, a profound change in proliferation kinetics was observed, indicating a release from density-dependent control of cell division. Additionally, the inhibitor abolished the increase of the biochemical differentiation marker acetylcholinesterase. The results suggest an important role of the ganglioside sialidase of the plasma membrane in the processes of proliferation control and differentiation in this neuronal cell system.

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PIP: The debate surrounding access to RU-486 in the US resurfaced in July 1992 when a pregnant California Resident attempted to challenge the Food and Drug Administration (FDA) import ban by going through customs at Kennedy International Airport with 12 prescription RU-486 pills she obtained in England. The pills were confiscated and the US Supreme Court denied the woman's request to recover the pills by a 7-2 vote. In 1993, on the 20th anniversary of the Roe v Wade abortion decision, President Clinton instructed the FDA to assess the real health and safety risks of the drug and rescind the ban if politics turns out to be the central issue. FDA has no criteria for measuring acceptable levels of safety, and drug approval is a lengthy process. Moreover, clinical trials are not initiated until a pharmaceutical company applies for FDA approval, which Roussel-Uclaf, RU-486's developer, has not done despite a wealth of safety and effectiveness data amassed in Europe. In fact, fearing a consumer boycott of its other products by US anti-abortion groups, Roussel-Uclaf has limited American researchers' access to RU-486. Despite the pro-choice climate of the Clinton Administration, it is unlikely that RU-486 will be available any time soon to US women, and physicians are concerned that a black market for the drug will emerge. This likelihood has serious consequences for people with Cushing's disease, nonmalignant brain tumors, breast cancer, and other medical conditions that may be responsive to RU-486. Given the experience with the introduction of oral contraceptives, marketed before long-term health consequences had been sufficiently explored, it is essential that FDA researchers investigate the impact of RU-486 on future children, future fertility, its interaction with other medications and contraceptives, and its effects on other bodily systems. At the same time, any risk-benefit assessment must be based on scientific merit, and access to Ru-486 cannot be denied on political or moral grounds.^ieng

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In order to investigate the influence of the autonomic nervous system on the immune response in rheumatic diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), we determined the number and the dissociation constants of beta 2-adrenergic receptors (beta 2R) on peripheral blood mononuclear cells (PBMC) in patients with RA characterized by either low or high disease activity, patients with SLE, and healthy age-matched controls by means of a radioligand binding assay with [125I]iodocyanopindolol. The number of beta 2R was significantly decreased in all three patient groups as compared with the healthy controls. In SLE patients, a significant negative correlation between beta 2R and the anti-ds-DNA antibody titre was observed (r = -0.57, P < 0.01). These data demonstrate the close correlation between the number of beta 2R on PBMC and the extent of disease activity in patients with RA and SLE and suggest an involvement of the autonomic nervous system in the pathogenesis of rheumatic disorders.

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