Splinting or surgery for carpal tunnel syndrome? Design of a randomized controlled trial [ISRCTN18853827]

Background  

Carpal tunnel syndrome is a common disorder, which can be treated with surgery or conservative options. However, there is insufficient evidence and no consensus among physicians with regard to the preferred treatment for carpal tunnel syndrome. Therefore, a randomized controlled trial is conducted to compare the short- and long-term efficacy of surgery and splinting in patients with carpal tunnel syndrome. An attempt is also made to avoid the (methodological) limitations encountered in earlier trials on the efficacy of various treatment options for carpal tunnel syndrome.     

The genus Pyrus L. (Rosaceae) in south-west Europe and North Afkica

A multivariate morphometric study of the genus Pyrus in south-west Europe and North Africa shows that five species may be recognized in the area: P. bourgaeana Decne., P. communis L., P. cordata Dew., P. spinosa Forssk, and P. nivalis Jacq. Some valuable characters for identification of these species are proposed. In particular the width of fruit peduncle, petal size, leaf width and petiole length served to discriminate the taxa. Several names such as P. gharbiona Trab., P. cossonii Rehder (|M= P. longipes Balansa ex Coss. & Durieu) and P. boisseriana Buhse, are regarded as synonyms of P. cordata , while P. marnormis Trab. of P. bourgaeana. Consequently a check-list and a key to these species are provided.     

Thioltransferase in human red blood cells: purification and properties

Thioltransferase activity was identified and the enzyme purified to apparent homogeneity from human red blood cells. Activity was measured as glutathione-dependent reduction of the prototype substrate hydroxyethyl disulfide; formation of oxidized glutathione (GSSG) was coupled to NADPH oxidation by GSSG reductase (1 unit of activity = 1 mumol/min of NADPH oxidized). The thioltransferase-GSH-GSSG reductase system was shown also to catalyze the regeneration of hemoglobin from the mixed disulfide hemoglobin-S-S-glutathione (HbSSG) and to reactivate the metabolic control enzyme phosphofructokinase (PFK) after oxidation of its sulfhydryl groups. On a relative concentration basis, thioltransferase was about 1200 times more efficient than dithiothreitol in reactivation of phosphofructokinase; e.g., 500 microM DTT was required to effect the same extent of reactivation as that of 0.4 microM TTase. The GSH plus GSSG reductase system without thioltransferase was ineffective for reduction of HbSSG or reactivation of PFK. The average amount of thioltransferase in intact erythrocytes was calculated to be 4.6 units/g of Hb at 25 degrees C. This level of activity is about the same as those of other enzymes that participate in sulfhydryl maintenance in red blood cells, such as GSSG reductase and glucose-6-phosphate dehydrogenase. These results suggest a physiological role for the thioltransferase in erythrocyte sulfhydryl homeostasis. Certain properties of the human erythrocyte thioltransferase resemble those of other mammalian thioltransferase and glutaredoxin enzymes. Thus, the human erythrocyte enzyme, purified about 28,000-fold to apparent homogeneity, is a single polypeptide with a molecular weight of 11,300. Its N-terminus is blocked, it is heat stable, and it contains four cysteine residues per protein molecule. However, the human erythrocyte thioltransferase is a distinct protein based on its amino acid composition. For example, it contains no methionine residues; whereas the related mammalian enzymes described to date have at least one internal methionine residue in their largely homologous sequences.     

Cultured endothelial cells produce heparinlike inhibitor of smooth muscle cell growth

Using cultured cells from bovine and rat aortas, we have examined the possibility that endothelial cells might regulate the growth of vascular smooth muscle cells. Conditioned medium from confluent bovine aortic endothelial cells inhibited the proliferation of growth-arrested smooth muscle cells. Conditioned medium from exponential endothelial cells, and from exponential or confluent smooth muscle cells and fibroblasts, did not inhibit smooth muscle cell growth. Conditioned medium from confluent endothelial cells did not inhibit the growth of endothelial cells or fibroblasts. In addition to the apparent specificity of both the producer and target cell, the inhibitory activity was heat stable and not affected by proteases. It was sensitive flavobacterium heparinase but not to hyaluronidase or chondroitin sulfate ABC lyase. It thus appears to be a heparinlike substance. Two other lines of evidence support this conclusion. First, a crude isolate of glycosaminoglycans (TCA-soluble, ethanol-precipitable material) from endothelial cell-conditioned medium reconstituted in 20 percent serum inhibited smooth muscle cell growth; glycosaminoglycans isolated from unconditioned medium (i.e., 0.4 percent serum) had no effect on smooth muscle cell growth. No inhibition was seen if the glycosaminoglycan preparation was treated with heparinase. Second, exogenous heparin, heparin sulfate, chondroitin sulfate B (dermatan sulfate), chondroitin sulfate ABC, and hyaluronic acid were added to 20 percent serum and tested for their ability to inhibit smooth muscle cell growth. Heparin inhibited growth at concentrations as low as 10 ng/ml. Other glycosaminoglycans had no effect at doses up to 10 μg/ml. Anticoagulant and non- anticoagulant heparin were equally effective at inhibiting smooth muscle cell growth, as they were in vivo following endothelial injury (Clowes and Karnovsk. Nature (Lond.). 265:625-626, 1977; Guyton et al. Circ. Res. 46:625-634, 1980), and in vitro following exposure of smooth muscle cells to platelet extract (Hoover et al. Circ. Res. 47:578-583, 1980). We suggest that vascular endothelial cells may secrete a heparinlike substance in vivo which may regulate the growth of underlying smooth muscle cells.     

Role of NADPH and the NADPH-dependent methemoglobin reductase in the hydroxylase activity of human erythrocytes

Human erythrocytes were shown previously to catalyze the oxyhemoglobin-requiring hydroxylation of aniline, and the reaction was stimulated apparently preferentially by NADPH in the presence of methylene blue (K. S. Blisard and J. J. Mieyal,J. Biol. Chem.254, 5104, 1979). The current study provides a further characterization of the involvement of the NADPH-dependent electron transport system in this reaction. In accordance with the role of NADPH, the hydroxylase activity of erythrocytes or hemolysates from individuals with glucose-6-phosphate dehydrogenase deficiency (i.e., with diminished capacity to form NADPH) displayed decreased responses to glucose or glucose 6-phosphate, respectively, in the presence of methylene blue in comparison to samples from normal adults; maximal activity could be restored by direct addition of NADPH to the deficient hemolysates. Kinetic studies of the methylene blue-stimulated aniline hydroxylase activity of normal hemolysates revealed a biphasic dependence on NADPH concentrations: a plateau was observed at relatively low concentrations (K_m^NADPH ~ 20 μm), whereas saturation was not achieved at the higher concentrations of NADPH. The latter low efficiency phase (i.e., at the higher concentrations of NADPH) could be ascribed to a direct transfer of electrons from NADPH to methylene blue to hemoglobin. The high efficiency phase suggested involvement of the NADPH-dependent methemoglobin reductase; accordingly 2′-AMP, an analog of NADP⁺, effectively inhibited this reaction, but the pattern was noncompetitive. This behavior is suggestive of a mechanism by which both NADPH and methylene blue are substrates for the reductase and interact with it in a sequential fashion. The kinetic patterns observed for variation in NADPH concentration at several fixed concentrations of methylene blue, and vice versa, are consistent with this interpretation.     

Subcellular localization of DNA-binding protein BA by immunofluorescence and immunoelectron microscopy

Nonhistone protein BA has been shown to decrease in amount in the chromatin of growth- stimulated normal rat liver (Yeoman et al. 1975. Cancer Res. 35:1249-1255) and in mitogen-stimulated normal human lymphocytes (Yeoman et al. 1976. Exp. Cell Res. 100:47- 55.). Subsequently, protein BA was purified and was shown to prefer to bind to double- stranded A-T-rich DNAs (Catino et al. 1978. Biochemistry. 17:983-987.). Immunization of rabbits with highly purified protein BA has resulted in the production of a specific antibody. A specific immunoreactivity for chromosomal protein BA has been demonstrated by immunoelectrophoresis and double antibody immunoprecipitation analysis with rabbit anti-BA immunoglobulin and IgG fractions. Light microscope examination of normal rat liver crysections by the indirect immunofluorescence procedure has demonstrated a cytoplasmic as well as a nuclear localization for protein BA with a pronounced perinucleolar fluorescence. Immunoelectron microscopy employing the peroxidase antiperoxidase method of antigen localization has confirmed the immunofluorescence data and has show a heterochromatin localization for protein BA. The relationship of the localization of protein BA to gene control in quiescent cells or to configurations of heterochromatin as well as the marked reduction in the amounts of protein BA which occur in stimulated growth states remains to be defined.