Hand injury without any deficit: Is systematic surgical exploration justified?

Out of 100,000 inhabitants, 700 to 4000 suffer a hand wound each year. Numerous hand wounds that may not have a clinically evaluated deficit, actually have damage to a major structure after surgical exploration in the operating room (OR). The aim of our study was to evaluate the incidence of major structure damage within a population of patients presenting a hand wound with no deficit on the clinical examination. Every patient older than 12 years, consulting for a wound deeper than the dermis with no clinical signs of major structure damage underwent surgical treatment and exploration of the wound under regional anesthesia in the OR. After each surgery, the surgeon filled out an anonymous study form describing the wound characteristics and the potential findings of major structure damage. Of the 145 wounds with normal clinical examination, we found that 58.6% had a major structure damaged. Given that damage to any major structure in the hand can lead to functional sequela, and the fact that a well-conducted clinical examination by a qualified hand surgeon is not sufficient to eliminate major structure damage, we recommend systematic surgical exploration of hand wounds, even when no clinical deficit is evident. LEVEL OF EVIDENCE III.: Type of sudy: diagnostic study.

Simplified internal fixation of fifth metacarpal neck fractures.

BACKGROUND: Fifth metacarpal neck fractures (boxer's fractures) are common injuries that contribute 20% of all hand fractures. Divergent percutaneous pinning (bouquet fixation) as described by Foucher has gained popularity but is challenging and at times arduous, as it requires the insertion of several slender K-wires into a narrow medullary canal. Here, we report on a simplified technique in which a single thick K-wire is inserted. TECHNIQUE: An 18/10 K-wire is bent at one end then mounted on a drill chuck. The incision is performed and the entry hole created using the K-wire, which is then advanced along the medullary canal. After reduction of the metacarpal head using the Jahss manoeuvre, the K-wire is inserted across the fracture site into the subchondral bone. Any persistent rotational malalignment is corrected by rotating the metacarpal around the K-wire. Immobilisation is by buddy taping covered by a resin guard. METHODS: We collected follow-up data for 30 patients treated using our technique, at a mean age of 32 years. RESULTS: 90 days after surgery, the fracture was healed in all patients. No patients had rotational malalignment. Mean operative time was 14minutes. No complications were recorded. DISCUSSION: The use of a single thick K-wire proved simple, effective, reproducible, and rapid. No rotational malalignment occurred. This technique is faster and easier to perform than divergent pinning with multiple K-wires. CONCLUSION: This technique can be used to treat fifth metacarpal neck fractures.

Accessory extensor pollicis longus: A rare tendon anomaly.

This report provides a complete review of a rare anatomical variation, the accessory extensor pollicis longus (EPL) tendon and its clinical significance. We will describe a case of an asymptomatic accessory EPL that was found incidentally during surgery with a tendon located in the fourth extensor compartment. Pulling on it induced extension of the thumb interphalangeal joint. Very few cases of accessory EPL have been previously reported with various muscle origins and tendon insertions. In the literature, three symptomatic cases of accessory EPL were reported with a tendon running in a compartment other than the fourth. Although this variation is asymptomatic in most cases, knowledge of its existence might be useful in routine procedures to avoid inadvertent tendon damage, or during tendon repair.

Triple-bundle anatomical reconstruction using the coracoacromial ligament and the short head of biceps tendon to stabilize chronic acromioclavicular joint dislocations: A cadaver feasibility study.

INTRODUCTION: In cases of chronic acromioclavicular joint separation, the biomechanical properties of anatomical reconstructions are closer to the native configuration than the Weaver-Dunn procedure. Consequently, the radiological and clinical outcomes are better. However, an additional incision is needed to harvest the graft, which increases the procedure's morbidity. HYPOTHESIS: Triple-bundle reconstruction can be performed with the coracoacromial ligament (CAL) and the semi conjoined tendon (SCT). MATERIAL AND METHODS: Bilateral dissection was performed on the upper limb of six fresh-frozen cadavers. Measurements useful to the procedure were taken on one limb, specifically the minimum graft length needed and the available length. The surgical procedure was performed on the other limb. The proximally based SCT was passed through the base of the coracoid process, then divided into two strips tightened from the superior aspect of the coracoid process to the clavicular insertion points of the conoid and trapezoid ligaments. The CAL was detached from the coracoid process and then secured in the medullary canal of the clavicle, after its lateral one-quarter was resected (i.e., 10mm). RESULTS: The mean length of the SCT was 101.7±7.6mm (95.1-114.5) and the mean length of the CAL was 35.3±4.7mm (28.7-42.5). The SCT length needed for this reconstruction was 58±4.3mm (51.5-62) medially and 60.3±4.6mm (54.3-66.3) laterally. The procedure was feasible in all six cadavers with an average excess length of 39.9±5.7mm (32.2-47) for the conoid bundle, 37.6±5mm (31-45.1) for the trapezoid ligament and 6±2.7mm (3-9.5) for the CAL. DISCUSSION: Triple-bundle anatomical reconstruction using the SCT and CAL is feasible. However, the strength of this construct must be evaluated biomechanically before it can be used clinically. LEVEL OF EVIDENCE: Not applicable - cadaver study.

Minimum 10-year clinical and radiological follow-up of trapeziectomy with interposition or suspensionplasty for basal thumb arthritis.

HYPOTHESIS: The aim of this article is to analyze clinical and radiological outcomes of trapeziectomy performed for basal thumb arthritis after a minimum follow-up of 10 years to gain further insight from shorter and medium-term studies reporting satisfactory evolution. METHODS: We reviewed 67 trapeziectomies, operated on by the same senior surgeon after a minimum follow-up of 10 years. The sample included 16 cases of suspensionplasty and 51 interpositions. Clinical outcome evaluated strength, pain, joint amplitude, Kapandji opposition score, Disabilities of the Arm, Shoulder and Hand score, complications and revision surgery. Radiological evaluation criteria included osteoarthritis and collapse of the trapezial void. RESULTS: After a 10-year follow-up, clinical results remained stable despite radiological degradations. Long-term clinical outcomes of trapeziectomy for basal thumb arthritis are very positive, with interpositioning as an isolated procedure appearing, clinically, to be the preferred treatment despite greater radiological degradation when compared to suspensionplasty. CONCLUSION: In addition to offering insight into minimum 10-year follow-up, this study also pinpoints this paradoxical dissociation of clinical-radiological outcomes. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic III.

[Nerve injuries associated with distal radius fractures]. / Lésions nerveuses associées aux fractures de l'extrémité distale du radius.

Nerve damage is a common complication of distal radius fractures. It may be a result of the injury event or be iatrogenic. It is the source of disability and potential handicap. There is little published data on this topic and no study has validated the strategies needed to prevent or manage these nerve-related complications. There is no consensus on treatment. Prevention requires a good knowledge of the various surgical approaches and rigorous fracture fixation technique. The objective of this article is to take stock of recent data from the scientific literature.

Isoindolines: a new series of potent and selective endothelin-A receptor antagonists.

1,3-Disubstituted isoindolines have been discovered as a new class of potent functional ET(A) selective receptor antagonists through pharmacophore analysis of existing nonpeptide endothelin antagonists. The structure-activity relationships for both the trans and the cis series of isoindolines are discussed.

Anilides of (R)-trifluoro-2-hydroxy-2-methylpropionic acid as inhibitors of pyruvate dehydrogenase kinase.

The optimization of a series of anilide derivatives of (R)-3,3, 3-trifluoro-2-hydroxy-2-methylpropionic acid as inhibitors of pyruvate dehydrogenase kinase (PDHK) is described that started from N-phenyl-3,3,3-trifluoro-2-hydroxy-2-methylpropanamide 1 (IC(50) = 35 +/- 1.4 microM). It was found that small electron-withdrawing groups on the ortho position of the anilide, i.e., chloro, acetyl, or bromo, increased potency 20-40-fold. The oral bioavailability of the compounds in this series is optimal (as measured by AUC) when the anilide is substituted at the 4-position with an electron-withdrawing group (i.e., carboxyl, carboxyamide, and sulfoxyamide). N-(2-Chloro-4-isobutylsulfamoylphenyl)-(R)-3,3, 3-trifluoro-2-hydroxy-2-methylpropionamide (10a) inhibits PDHK in the primary enzymatic assay with an IC(50) of 13 +/- 1.5 nM, enhances the oxidation of [(14)C]lactate into (14)CO(2) in human fibroblasts, lowers blood lactate levels significantly 2.5 and 5 h after oral doses as low as 30 micromol/kg, and increases the ex vivo activity of PDH in muscle, kidney, liver, and heart tissues. However, in contrast to sodium dichloroacetate (DCA), these PDHK inhibitors did not lower blood glucose levels. Nevertheless, they are effective at increasing the utilization and disposal of lactate and could be of utility to ameliorate conditions of inappropriate blood lactate elevation.

Differential inhibition of the prejunctional actions of angiotensin II in rat atria by valsartan, irbesartan, eprosartan, and losartan.

The effects of valsartan and other nonpeptide angiotensin II type 1 (AT(1)) receptor blockers on the prejunctional actions of angiotensin II were investigated in the isolated left atria of rat. Norepinephrine stores in rat atria were loaded with [(3)H]norepinephrine, and neuronal norepinephrine release was deduced from the radioactivity efflux. Angiotensin II (10(-9) to 10(-6) M) produced concentration-dependent enhancement of the electrical stimulation-induced efflux of [(3)H]norepinephrine from the preparation. Pretreatment of tissues with valsartan, irbesartan, eprosartan, or losartan (10(-8) to 10(-6) M) produced concentration-dependent inhibitions of the stimulation-induced efflux of radioactivity observed in the presence of angiotensin II (10(-7) M). The AT(1) receptor blockers did not decrease the "basal stimulation-induced overflow of radioactivity but rather selectively inhibited the angiotensin II-mediated augmentation of the response. Regression analyses of the inhibition of the angiotensin II-mediated response by valsartan, irbesartan, eprosartan, and losartan revealed corresponding log IC(50) values (log M, with 95% confidence intervals) of -7.78 (-8.19, -7.51), -7.65 (-8.02, -7.40), -7.12 (-7. 37, -6.86), and -6.75 (-7.00, -6.40), indicating that the IC(50) values for valsartan and irbesartan are significantly lower than those for eprosartan and losartan. Thus, valsartan is a potent inhibitor of the prejunctional facilitatory effect of angiotensin II on the release of norepinephrine from peripheral sympathetic nerves. This implies that the therapeutic domain of valsartan may be extended to include pathophysiological conditions such as congestive heart failure wherein prejunctional angiotensin II receptors apparently play a significant role. Whether the high potency of valsartan translates into a significant clinical advantage relative to the other agents tested remains to be ascertained.

Secondary amides of (R)-3,3,3-trifluoro-2-hydroxy-2-methylpropionic acid as inhibitors of pyruvate dehydrogenase kinase.

N'-methyl-N-(4-tert-butyl-1,2,5,6-tetrahydropyridine)thiourea, SDZ048-619 (1), is a modest inhibitor (IC(50) = 180 microM) of pyruvate dehydrogenase kinase (PDHK). In an optimization of the N-methylcarbothioamide moiety of 1, it was discovered that amides with a small acyl group, in particular appropriately substituted amides of (R)-3,3,3-trifluoro-2-hydroxy-2-methylpropionic acid, are inhibitors of PDHK. Utilizing this acyl moiety, herein is reported the rationale leading to the optimization of a series of acylated piperazine derivatives. Methyl substitution of the piperazine at the 2- and 5-positions (with S and R absolute stereochemistry) markedly increased the potency of the lead compound (>1,000-fold). Oral bioavailability of the compounds in this series is good and is optimal (as measured by AUC) when the 4-position of the piperazine is substituted with an electron-poor benzoyl moiety. (+)-1-N-[2,5-(S, R)-Dimethyl-4-N-(4-cyanobenzoyl)piperazine]-(R)-3,3, 3-trifluoro-2-hydroxy-2-methylpropanamide (14e) inhibits PDHK in the primary enzymatic assay with an IC(50) of 16 +/- 2 nM, enhances the oxidation of [(14)C]lactate into (14)CO(2) in human fibroblasts with an EC(50) of 57 +/- 13 nM, diminishes lactate significantly 2.5 h post-oral-dose at doses as low as 1 micromol/kg, and increases the ex vivo activity of PDH in muscle, liver, and fat tissues in normal Sprague-Dawley rats. These PDHK inhibitors, however, do not lower glucose in diabetic animal models.

Characterization of CGS 31447, a potent and nonpeptidic endothelin-converting enzyme inhibitor.

Optimization of an aminophosphonic acid series of compounds for inhibition of endothelin-converting enzyme (ECE) has led to the discovery of CGS 31447. This compound reversibly inhibited the activity of recombinant human ECE-1 with an IC50 value of 21 nM. The effect of CGS 31447 was not due to nonspecific chelation of the zinc ion at the catalytic center of ECE-1 by the phosphonic acid of the inhibitor. Determination of kinetic parameters of ECE-1 in the presence of 5-15 nM CGS 31447 revealed the competitive nature of the compound; a K1 of 7 nM was obtained. CGS 31447 infused at concentrations of 0.01, 0.1, and 1.0 microM inhibited the mean increase in big ET-1-induced pressor responses in isolated and perfused rat kidneys by 7, 39, and 68%, respectively, compared with the controls. These results demonstrate that CGS 31447 is a potent, reversible, and competitive inhibitor of ECE-1.

The unusual binding properties of the endothelin receptor antagonist CGS 27830 distinguishes receptor/agonist interactions.

CGS 27830 [meso-1,4-dihydro-5-methoxycarbonyl-2,6-dimethyl-4-(3- nitrophenyl)-3-pyridine carboxylic acid anhydride] is a nonpeptidic, insurmountable, endothelin (ET) receptor antagonist with approximately 10- to 20-fold selectivity for ETA receptors. CGS 27830 exhibits unusual binding properties which depend on the receptor and ligand: standard saturation binding experiments (coincubation of membranes with ligand in the absence or presence of antagonist) suggest that CGS 27830 is a competitive inhibitor of [125I]IRL 1620 binding to ETB receptors in rat cerebellar membranes (i.e., there was a change of apparent Kd with no change of maximum binding), but a noncompetitive inhibitor of [125I]IRL 1620 binding to ETB receptors in rat lung membranes (i.e., significant loss of total binding was observed). Although the antagonist appears to be a noncompetitive inhibitor of [125I]IRL 1620 binding to ETB receptors in rat lung membranes, CGS 27830 appears to be a competitive inhibitor of [125I]ET-1 binding to the same receptors as well as to ETA receptors in A7r5 cell membranes. Thus, CGS 27830 can distinguish [125I]IRL 1620 binding to ETB receptors in rat cerebellar and lung membranes, but not ET-1 binding to ETB receptors in these tissues. These unusual binding properties demonstrate that rat lung and cerebellum ETB receptors interact differently with IRL 1620 or ET-1.

Evidence that BKCa channel activation contributes to K+ channel opener induced relaxation of the porcine coronary artery.

The rank order of potency of a series of benzopyran and cyanoguanidine K+ channel openers (KCOs) for causing relaxation of the PGF2 alpha-precontracted porcine coronary artery was determined. Glyburide, an inhibitor of KATP channels, showed an apparent competitive inhibition of the vasorelaxant activity of the KCOs. The pA2 values of glyburide when cromakalim and CGP 14877 (P1060) were used as vasorelaxants were 7.66 and 7.83, respectively. Charybdotoxin (40 nM), an inhibitor of BKCa channels, also caused a significant inhibition of the cromakalim mediated relaxation of the porcine coronary artery. In order to clarify the site of action of these KCOs, we identified a K+ channel current in single porcine coronary arterial cells and measured channel activity in the presence of these compounds. The prominent K+ ion current in these cells had characteristics typical of the conventional large Ca(2+)-activated K+ channel (BKCa) present in other smooth muscle cells. Using symmetrical K+ concentrations, the channel had a conductance of 214 pS and was found to be sensitive to [Ca2+]i and membrane potential. The KCOs were found to reversibly increase the open probability (P(o)) of the channel without changing channel conductance. The potency of the KCOs to increase K+ channel opening was similar to the potency of these compounds to cause coronary artery relaxation. These results indicate that the porcine coronary artery contains the BKCa channel and that this channel, along with other types of K+ channels (KATP), mediate the vasorelaxant effects of K+ channel openers.

Delineation of endothelin receptor subtypes in rat and rabbit aortas.

The receptor subtypes mediating tension responses to endothelin-1 (ET-1) in isolated rat and rabbit aortic preparations were examined with various ET receptor antagonists. In the presence of 3 microM IRL 2500 (an ETB-selective antagonist), SB 209670 (an ETA/ETB antagonist) induced monophasic inhibitions of the ET-1 dose-response curves of both rat (pKB 9.1) and rabbit aortas (pKB 8.9). In the presence of IRL 2500, PD 156707 (an ETA antagonist) also caused a similar monophasic inhibition of the agonist-induced dose-response curve of the rat aorta (pKB 7.7) but produced a biphasic inhibition of the curve obtained with the rabbit aorta. PD 156707, however, produced monophasic inhibitions of the ET-1-induced dose-response curve of rabbit aortas pretreated either with BQ 788 (an ETB-selective antagonist) or desensitized with sarafotoxin S6c (an ETB-selective agonist). The receptor subtypes mediating the contractile responses to ET-1 were further characterized by examining the effects of the antagonists on the binding of [125I]ET-1 to these two tissues. In the presence of 1 nM IRL 2500, SB 209670 displaced [125I]ET-1 binding in both rat and rabbit aortic membrane preparations in a monophasic manner, with similar potencies (IC50 1.2-1.6 nM). Similar results were also ontained with PD 156707 in rat aortic membrane (IC50 0.27 nM). In contrast, the data obtained with PD 156707 using rabbit aortic membrane were best-fitted with a two-site model (site 1, IC50 0.21 nM, 67% of Bmax; site 2, 100 nM and 33%, respectively). Therefore, the constrictor response to ET-1 in the rat aorta is mediated exclusively by the ETA receptor, whereas that in the rabbit aorta is additionally mediated by an ETB receptor subtype that is sensitive to SB 209670 and BQ 788 but insensitive to IRL 2500.

Characterization of a potent and selective endothelin-B receptor antagonist, IRL 2500.

IRL 2500 [N-(3,5-dimethylbenzoyl)-N-methyl-(D)-(4-phenylphenyl)-alany l-L- tryptophan] inhibited the binding of [125I]-endothelin-1 (ET-1) to human ETB (IC50 1.3 +/- 0.2 nM) and ETA (IC50 94 +/- 3 nM) receptors expressed in transfected Chinese hamster ovary (CHO) cells. In in vitro studies, IRL 2500 inhibited the sarafotoxin S6c (STX6c)-mediated contraction of the dog saphenous vein (pKb 7.77) and the STX6c-induced relaxation of the preconstricted rabbit mesenteric artery (pKb 6.92). In the anesthetized rat, IRL 2500 (10 mg/kg, i.v.) inhibited the initial transient decrease in mean arterial pressure (MAP) induced by the ETB-selective agonist IRL 1620 (0.5 nmol/kg, i.v.). IRL 2500 also attenuated the IRL 1620-mediated increase in renal vascular resistance (RVR) in the anesthetized rat. Therefore, IRL 2500 is a potent and selective ETB receptor antagonist that can be used to delineate ET responses mediated by the ETB receptor.

Inhibition by nickel of endothelin-1-induced tension and associated 45Ca movements in rabbit aorta.

Contractions induced by 10 nM endothelin-1 (ET) in the rabbit aortic media intimal layer were inhibited by prior exposure to 100 microM Ni++ (33.1%) or to a Ca(++)-free buffer (80.2%) but were unaffected by pretreatment with 0.1 microM nifedipine. Contractions elicited by phenylephrine (1 nM-100 microM) or K+ (10-50 mM) were not inhibited by 100 microM Ni++ but those induced by ET in tissues submaximally precontracted with 20 mM K+ were selectively antagonized by the divalent cation. The mechanism for the inhibitory action of Ni++ was ascertained by an examination of the effects of the cation on ET-induced alterations in the cellular distribution and mobilization of Ca++. Efflux of 45Ca from the muscle into a solution without added Ca++ was not altered by ET. Total or cellular 45Ca uptake (uptake after exposure to La and low temperature), at either low- or high-affinity sites in resting muscles was also not affected by the peptide. However, low-affinity cellular 45Ca retention in muscles depolarized with high K+ levels (160 mM) was significantly enhanced (45.1%) by ET. Ni++ did not alter 45Ca retention in control and K(+)-treated muscles but it blocked the additional incremental 45Ca uptake associated with ET (in the presence of high K+). Thus, Ni++ produced a selective blockade of an ET-activated Ca++ influx pathway, distinct from the dihydropyridine-sensitive L-type Ca++ channels, in rabbit aortic smooth muscle. This action by Ni++ apparently inhibits subsequent contractile responses of the muscle to ET.

Functionally distinct endothelin B receptors in vascular endothelium and smooth muscle.

IRL 1620 (Suc-[Glu9,Ala11,15]-ET-1 (8-21)) (0.1 nM - 1 microM), a novel ETB-selective endothelin (ET) agonist, produced endothelium-dependent relaxations in precontracted rabbit mesenteric artery (2 nM, EC50) and endothelium-independent contractions in porcine coronary artery (18 nM, EC50). ET-3 (0.1 nM-10 nM) produced qualitatively similar responses in the two tissues. The maximal contractions induced by IRL 1620 or ET-3 were substantially smaller (< 20%) than that produced by ET-1. BQ-123 (1 microM), an ETA receptor antagonist, inhibited responses to ET-1 without affecting IRL 1620- or ET-3-induced responses in either tissue. Thus functionally distinct ETB receptors mediating vasodilator and vasoconstrictor effects are located on the vascular endothelium and smooth muscle, respectively. The overall effect of ETB receptor activation on vascular tone is tissue-specific and presumably reflects differing receptor distribution at the two sites.

A soluble protease identified from rat kidney degrades endothelin-1 but not proendothelin-1.

Endothelin-1 (ET-1) is a potent peptidic vasoconstrictor. This peptide has been shown to be cleared rapidly by the kidney. The purpose of the present study was to assess the involvement of renal proteolytic enzymes in the clearance/degradation of ET-1. Incubation of ET-1 with the cytosolic fraction of rat kidney homogenate resulted in a decrease of contractile activity on rabbit aortic rings when compared to the untreated ET-1. This cytosolic fraction was chromatographed by anion-exchange and concanavalin A columns. The partially purified enzyme cleaved off the C-terminal tryptophan of ET-1 rapidly, resulting in a peptide which is three orders of magnitude weaker in potency than ET-1 in causing smooth muscle contraction. In contrast, proendothelin-1 was not degraded by this endothelin degradation enzyme (EDE). The effects of EDE on other vasoactive peptides were also examined. The C-terminal tyrosine of atrial natriuretic peptide was cleaved by EDE, but the biological activity of the resulting peptide was not significantly changed. Angiotensin II was not a substrate for EDE. The EDE was shown to be different from both carboxypeptidases A and B based on the HPLC analysis of the degradation products of ET-1 produced by these enzymes. In addition, these enzymes displayed different sensitivities toward a carboxypeptidase inhibitor from potato tuber. These results suggest that this previously unidentified enzyme inactivates ET-1 effectively and that it may play a role in modulating the levels of ET-1 in the kidney.