The cutaneous silent period in carpal tunnel syndrome.

OBJECTIVES: The cutaneous silent period (CSP), a sustained voluntary contraction following a painful stimulus applied over the appropriate dermatome produces a brief period of electrical silence, may be useful if the routine nerve conduction studies and needle electromyography are insufficient to diagnose entrapment neuropathies. MATERIAL AND METHODS: To investigate whether symptomatic or asymptomatic patients with entrapment neuropathies are differed in terms of CSP, one hundred fifty four hands of 58 patient and 19 controls were studied according to the clinical and electrophysiological findings. RESULTS: CSP latency and duration could be affected in severe forms of entrapment neuropathies. However, even in patients with dysesthetic pain -which lead to the belief that small fibers may be involved-, results of electrophysiological evaluation could not support the clinical findings. CONCLUSION: In this study it was suggested that CSP studies provide no additional information in entrapment neuropathies.

A colourimetric enzyme-linked sandwich assay for the detection of human platelets bound to a fibrinogen-coated surface.

A colourimetric enzyme-linked sandwich assay has been developed to investigate the binding of human platelets to fibrinogen. The presence of platelets bound to fibrinogen-coated plastic can easily be detected and quantitated. Platelets treated with chymotrypsin to expose the fibrinogen receptor, are fixed with paraformaldehyde, and stored frozen. The detection sandwich consists of a mouse monoclonal antibody directed against the human platelet CD9 antigen, and a rabbit anti-mouse immunoglobulin conjugated to the enzyme alkaline phosphatase. The cleavage of the phosphatase substrate p-nitrophenyl phosphate can be monitored colourimetrically. The data presented provide evidence that this method is capable of detecting platelet-fibrinogen binding in a physiologically relevant manner. The binding is inhibited by EDTA or excess fibrinogen. The fibrinogen alpha and gamma chain peptides, RGDS and LGGAKQAGDV, and the snake venom echistatin are also inhibitory with IC50 values of 135 microM, 1.8 mM and 100 nM respectively.

Two sulphonated dye compounds which compete for inositol 1,4, 5-trisphosphate binding to rat liver microsomes: effects on 5'-phosphatase activity.

The ability of heparin to interact with the Ins 1,4,5-P3 receptor is dependent on its chain length and degree of sulphation. Here we report results obtained with two sulphonated dye compounds of known structures and molecular weights below 1000, cibacron blue and Patent blue. Both compounds compete for Ins 1,4,5-P3 binding to rat liver microsomes and also inhibit Ins 1,4,5-P3 5'-phosphatase activity in the same preparation. Comparison with the effects of heparin show these to be two separate actions of the compounds.

The effect of heparin on the inositol 1,4,5-trisphosphate receptor in rat liver microsomes. Dependence on sulphate content and chain length.

Heparin is known to inhibit the binding of inositol 1,4,5-trisphosphate (Ins 1,4,5-P3) to high-affinity binding sites and to inhibit Ins 1,4,5-P3-induced Ca2+ release from intracellular membrane-bound stores [(1987) J. Biol. Chem. 262, 12132-12136; (1987) FEBS Lett. 228, 57-59]. We have performed studies to clarify the structural requirements for this action of heparin in rat liver microsomes. Both N- and O-linked sulphate groups contribute to binding activity, since de-N-sulphated heparin was without effect on the Ins 1,4,5-P3 receptor whereas a polyxylan bearing only O-linked sulphates (pentosan polysulphate) was as active as heparin. Therefore, the density of negative charge contributed by sulphate groups is important for the binding of heparin. Heparins with high and low affinity for antithrombin III both inhibited Ins 1,4,5-P3 binding. There was a strong dependence on chain length, since binding activity decreased dramatically as the size of the heparin chain was reduced below that of 18-24 monosaccharide units.

Subcellular localization of 111In in human and rabbit platelets.

In order to examine the subcellular distribution of 111In in 111In-oxine-labeled human and rabbit platelets, we employed a hypothetical grain technique of EM autoradiography analysis. The results indicate that in the rabbit 111In was concentrated within the platelet dense bodies, particularly when the platelets had been labeled in a plasma-free system. Under comparable conditions of labeling, human platelets appeared to accumulate almost all the radiolabel within the cytosol. Using inhibitors of 5-hydroxytrptamine (5-HT) uptake, i.e., cloimipramine, ouabain, sodium fluoride, p-chloromercuribenzoate, and reserpine, we were unable to demonstrate an active uptake process in either species. Both collagen and thrombin were able to cause dose-dependent release of radioactivity from the labeled rabbit platelets only. In the case of collagen, this mimicked endogenous 5-HT release and was inhibited by indomethacin. These results and their implications are discussed.

The effect of sulphinpyrazone and its metabolites on platelet function in vitro and ex vivo.

The thioether metabolite of sulphinpyrazone is between 8 and 13 times more potent than the parent compound as a competitive inhibitor of human, guinea pig and rabbit platelet aggregation induced by sodium arachidonate. Of the other known metabolites, the sulphone is approximately equipotent and the p-hydroxy compounds are much less potent that sulphinpyrazone itself. Malondialdehyde biosynthesis from sodium arachidonate by washed human platelets and collagen-induced aggregation of all three species is also inhibited by the thioether. It is 10 times more potent than sulphinpyrazone. ADP-induced aggregation is not affected by sulphinpyrazone, its thioether metabolite, nor the other metabolites. After intravenous administration of the thioether metabolite to groups of guinea pigs the inhibitory effect on sodium arachidonate-induced platelet aggregation ex vivo was long lasting (up to 24 h). In view of the recent information about the metabolism of sulphinpyrazone to its thioether in guinea pigs, we conclude that the thioether metabolite is the substance responsible for the prolonged effect of sulphinpyrazone on platelet fuction in this species and in man.

The effects of two different dosage regimens of sulphinpyrazone on platelet function ex vivo and blood chemistry in man.

When sulphinpyrazone (either 200 mg q.d.s. for 7 days or 400 mg b.d.s. for 5 days) was administered to human volunteers, inhibition of platelet function was observed ex vivo. The inhibitory effect was measured by the increase in the concentration of sodium arachidonate required to cause platelet aggregation and a decrease in the biosynthesis by the platelets of malondialdehyde from added sodium arachidonate. ADP-induced primary platelet aggregation was statistically significantly inhibited only on 1 day of the two studies. The inhibitory effect did not correlate with the plasma concentrations of unchanged sulphinpyrazone nor with its sulphone metabolite but correlated with the plasma concentration of the thioether metabolite (r = 0.577, p less than 0.001). Platelet count, plasma fibrinogen, beta-thromboglobulin, urea and creatinine concentrations were not changed by the drug but there was a clinically insignificant increase in bleeding time in all but one subject.

The effects of glutaraldehyde and formaldehyde fixation on the retention and subcellular location of [3H]5-hydroxytryptamine in rabbit platelets: a study using liquid scintillation counting and E.M. autoradiography.

The retention and loss of [3H]5-hydroxytryptamine (5-HT) from rabbit platelets during fixation was studied using liquid scintillation counting and quantitative electron-microscopic autoradiography. The results were at variance with previously reported data on human platelets. Following treatment of the platelets with either 2.0% formaldehyde or 2.5% glutaraldehyde for 2 min or 1 h it was found that a significantly increased proportion of the radioactivity was lost from treated as compared with untreated platelets. Using a method of analysis which accounts for cross-scatter of decay particles between cell compartments, electron-microscopic autoradiography revealed that 50% of the radioactivity following incubation of platelets with [3H]5-HT was associated with dense bodies and 30% in the cytoplasm when fixation was in formaldehyde or glutaraldehyde. The only major difference in the labelling pattern was that whereas glutaraldehyde appeared to retain no activity in the surface connected system the latter contained 12% of total retained activity following fixation with formaldehyde.

A qualitative and quantitative study of monocytes in patients with malignant solid tumors.

Monocytes from 21 patients with cancer of the lung and cancer of the prostate were studied prior to treatment. The absolute circulating monocyte count, serum lysozyme levels and monocyte IgG surface receptors were normal at all stages of the disease. Monocyte chemotaxis was defective in 45% of the patients. Serum chemotatic factor inactivator(s) that inhibit chemotaxis of normal monocytes were detected in 90% of the patients. In two of four patients the chemotactic factor(s) disappeared following surgical removal of localized tumors. The results of the chemotaxis studies may explain the data of defective delayed hypersensitivity reactions frequently seen in patients with malignancies. The defective chemotaxis and the presence of chemotatic factor inactivator(s) may interfere with the ability of monocytes to accumulate as macrophages in tumor sites.

Ischemic versus cytotoxic damage in the white graft reaction. Its relationship to hyperacute kidney rejection.

"White" skin grafts on appropriately sensitized allografted mice are ischemic and necrotic. The ischemia occurs because of failure to form anastomoses between host and graft vessels. This failure is not due to altered host vascular function but correlated with obliterative (nonthrombotic, non-necrotizing) changes of graft vessels at the interface. It appears that the ischemia of white grafts, in contrast to that observed in hyperacutely rejected renal allografts, is not the cause of the necrosis, but vice versa. The necrosis of white grafts, which begins during the first 24 hr after their placement, is probably related to a very early immune assault on the graft as a whole. The nature and the pathways of this immune assault are not the subject of this study.