Collagenase clostridium histolyticum in patients with Dupuytren's contracture: results from POINT X, an open-label study of clinical and patient-reported outcomes.

In POINT X, a study designed to reflect clinical practice and patient treatment choices, 254 European patients received open-label collagenase for Dupuytren's contracture. The most severely affected joint was treated first in 74% of patients. In total, 52%, 41%, 7%, and 1% of patients selected the little, ring, middle, and index finger, respectively; 79% had one or two joints treated. Only 9% of patients (n = 24) received 4 or 5 injections. The mean improvement in total passive extension deficit (TPED) was 34° on day 1, improving further by day 7 to 42°. This secondary improvement was maintained by day 90 and month 6. The mean number of injections/joint was 1.2 for the metacarpophalangeal joint and 1.25 for the proximal interphalangeal joint. Median time to recovery was 4 days; the mean improvement in hand function was clinically relevant as measured by the Unité Rhumatologique des Affections de la Main (URAM) score. In total, 87% and 86% of patients and physicians, respectively, were very satisfied or satisfied with treatment at month 6, although correlation between TPED and patient satisfaction was weak (Spearman -0.18, 95% CI -0.32 to -0.06). Collagenase was well tolerated, with 10 (3.9%) patients experiencing severe adverse events. As a real-world study, the POINT X findings can be generalized to the at-large population.

Differential effects of 2'-deoxyguanosine on peripheral blood mononuclear cell proliferation in healthy donors and Hashimoto's thyroiditis patients.

The aim of this study was to determine possible differences in peripheral blood mononuclear cells (PBMC) proliferation of healthy donors and Hashimoto's thyroiditis patients and whether a statistical approach to cell proliferation analysis might be used to discern the differences. The effect of a wide range of 2'-deoxyguanosine (dGuo) concentrations (0-1250 microM) on the mitogen-induced proliferation of PBMC was studied in healthy donors and Hashimoto's thyroiditis patients. Activity levels of purine nucleoside phosphorylase (PNP) and adenosine deaminase (ADA) in PBMC were also measured. For the first time in a study of these models of dGuo toxicity in vitro, the analysis of polynomial trends of orders from 1 to 7 was applied to evaluate cell proliferation. A dose-dependent inhibition of mitogen-induced PBMC proliferation was observed in both groups. Data for linear trend established that PBMC from Hashimoto's thyroiditis patients were more sensitive to dGuo toxicity than PBMC from healthy donors. A positive quadratic trend at low dGuo doses was found in the cell proliferation of Hashimoto's thyroiditis patients. A decrease in PNP activity (P < 0.025) and an increase in ADA activity (P < 0.005) was observed in PBMC of Hashimoto's thyroiditis group. The differences in PBMC proliferation subjected to dGuo toxicity between the two groups could be related with the distinct pattern of purine salvage enzymes observed.

Laser Doppler imaging of finger skin blood flow in patients after microvascular repair of the ulnar artery at the wrist.

Laser Doppler imaging is a new, non-invasive technique allowing the spatial distribution and the temporal variation of the skin blood flow to be monitored. A mean blood flow value over an area, such as the finger-tip in the present study, can also be calculated. Recordings from 12 patients with a sutured ulnar artery following trauma did not significantly differ from those obtained in 14 controls. Four patients with a ligated ulnar artery, however, showed a slower restitution of blood flow values after cold provocation. All sutured ulnar arteries were found to be patent, which confirms that microvascular reconstruction of an injury to the ulnar artery at the wrist is worthwhile.

Complete palmar dislocation of the lunate in rheumatoid arthritis. Avascularity without avascular changes.

We report a case of complete palmar dislocation of the lunate in a rheumatoid patient. X-rays showed a normal bone structure of the lunate without sclerosis or collapse and on MRI an almost normal signal intensity was found. The lunate was removed. Histological examination showed complete necrosis of both marrow and bone cells, and tetracycline labelling showed no fluorescence. This case illustrates that neither X-ray nor magnetic resonance imaging (MRI) can detect complete bone necrosis. When X-ray or MRI changes do occur, these are indications of cellular events following some degree of spontaneous revascularization.

Acutrak screw fixation versus cast immobilisation for undisplaced scaphoid waist fractures.

Fifty-three patients with less than 14 day-old, undisplaced fractures of the waist of the scaphoid were randomized to two groups. Twenty-eight patients were treated by immobilisation in a below elbow plaster cast for 10 weeks while 25 were treated by percutaneous insertion of an Acutrak standard screw. There were no statistically significant differences between the two treatment groups with regard to either the rate of union or the time to union. Patients who underwent surgery had a significantly better range of motion at 16 weeks but there were no significant differences for grip strength. Acute percutaneous internal fixation of undisplaced scaphoid waist fractures using the Acutrak screw allows early mobilisation without adverse effects on fracture healing.

Intraarticular lesions in distal fractures of the radius in young adults. A descriptive arthroscopic study in 50 patients.

We examined the frequency of associated chondral and ligament lesions in distal fractures of the radius in young adults (men 20-60 years, women 20-50 years). Fifty initially displaced fractures were examined arthroscopically. Chondral lesions were found in 16 patients (32%). All patients but one were found to have a ligamentous injury in the wrist. No major instability was found. The most frequent ligament tear was the triangular fibrocartilage complex in 39 cases (78%), with a statistical correlation to ulnar styloid fractures. The scapholunate ligament was partially or totally torn in 27 cases (54%). No correlation was found between specific fracture type and pattern of ligament injury. Chondral and ligamentous lesions were frequent and may explain poor outcomes after seemingly well-healed distal fractures of the radius. The ligament lesions should also be kept in mind when early mobilization of the distal fracture of the radius is considered.

Sixty five thumb replantations. A retrospective analysis of factors influencing survival.

Sixty five isolated thumb replantations and revascularisations for survival done at our department between 1977 and 1991 were studied retrospectively. The overall failure rate was 20% (13/65). The most important influence on outcome was the mechanism of injury. The failure rate for avulsed thumbs was 38% (6/16), for all other mechanisms of injury 14% (7/49). The failure rates for replantations and revascularisations for survival were similar, 18% (6/33) and 22% (7/32), respectively. The survival rate was independent on the level of injury, the failure rates for amputations at the levels of the proximal and distal phalangeal levels being 19% (6/31) and 21% (7/33), respectively. The presence of two patent arteries at the end of the operation (n = 11) was favourable for the prognosis, as all these thumbs survived. There was no corresponding relationship on the venous side. The use of vein grafts on the arterial or venous side was not associated with lower failure rate. Nine patients were reoperated on, one of them twice. Reoperation was worthwhile, the failure rate in reoperated thumbs being only 11%.

Morbidity of the pedicled groin flap. A retrospective study of 44 cases.

Forty four pedicled groin flaps, raised between 1986 and 1990 for the coverage of soft tissue defects of the hand and forearm, were retrospectively evaluated. Thirty eight (86%) were emergencies, roller injuries with skin avulsion being the main mechanism of injury. Local complications such as partial flap necrosis, infection, and seroma, developed in 11 patients (25%). Subsequent defatting was required in 38 (86%) of the flaps and four patients (9%) had secondary revisions of the donor sites. The median duration of hospital stay was 26 days (range 8-81), and 12 patients (27%) were discharged from hospital before division of the pedicle. General complications, including pneumonia (n = 2) and pulmonary embolism (n = 1) developed in five patients (11%), four of whom were 55 years old or more. One patient died of a myocardial infarction 15 days postoperatively. Our results indicate that other methods for skin coverage should be chosen for patients older than 50 years.

Pain drawing as an investigative tool in hand surgery.

Fifty consecutive patients referred to the departments of hand surgery in Malmö and Lund were asked to chart their pain on a diagram of the body before their first visit to the clinic. Three patients never answered the questionnaire and were excluded. The drawings were evaluated separately by a senior hand surgeon without access to the case records. In 19 of 47 cases (40%) the evaluation of the pain drawings agreed with the clinical diagnosis. In another 17% (8 of 47), in which the pain drawings had indicated a condition not related to hand surgery, clinical examination failed to establish a diagnosis. The evaluation of the drawings had a false negative rate of 4% (2 of 47). In the remaining 18 cases pain drawings did not give enough information for diagnosis because of the variety of symptoms. Pain drawing seems to be valuable in the evaluation of patients with chronic pain in the upper extremity.

Soft tissue sarcoma of the upper extremity: descriptive data and outcome in a population-based series of 108 adult patients.

We report a population-based, 29-year review of 108 adult patients with soft tissue sarcoma of the upper extremity who had a minimum follow-up period of 3 years. Fifty tumors were localized in the upper arm, 8 in the elbow, 40 in the forearm, and 10 in the hand. Thirty-four tumors were subcutaneous and 74 were deep-seated. The median tumor size was 6 cm. Malignant fibrous histiocytoma was the most common histotype (n = 43), and grade IV (on a 4-grade scale) was the most common malignancy grade (n = 54). All but 6 patients underwent surgery; limb-sparing surgery of the primary tumor was performed in 89 patients. Twenty-four patients were given adjuvant radiotherapy; 11 received adjuvant chemotherapy. Inadequate local treatment was more common in patients treated outside the tumor center. Local recurrence occurred in 15 of 28 with inadequate local treatment and in 16 of 74 patients with adequate local treatment (20 of the 39 patients treated outside the center and 11 of the 63 patients treated at the center). At the latest follow-up visit, 32 patients had developed metastases, giving a 5-year metastasis-free survival rate of 0.72. In a multivariate analysis, tumor size larger than 5 cm and vascular invasion emerged as independent prognostic factors. Patients without these 2 factors had excellent survival. When compared with soft tissue sarcoma of the lower extremity or trunk wall, tumors in the upper extremity were smaller at the time of diagnosis and had a higher 5-year metastasis-free survival rate.

Wrist flexion strength after excision of the pisiform bone.

Diseases of the pisiform triquetral (P-T) joint and the pisiform itself are often treated with excision of the pisiform bone. The flexor carpi ulnaris (FCU) tendon inserts on the volar aspect of the pisiform, suggesting a loss of strength in wrist flexion following excision of the bone. Isometric and dynamic, isokinetical measurements were made using a strain-gauge dynamometer (Cybex II). Slight postoperative reduction of wrist flexion strength, compared with the contralateral wrist, was noted but not of clinical significance. It is concluded that one should not refrain from excision of the pisiform bone for fear of considerable strength loss in wrist joint flexion.

Endothelium-dependent relaxation and effects of prostacyclin, endothelin and platelet-activating factor in human hand veins and arteries.

An altered release of endothelium-derived vasoactive factors has been implicated in several vasospastic conditions. Since the functional role of the endothelium in the hand vasculature is largely unknown, we examined the effects of 'endothelial removal' on vascular reactivity, and the effects of some 'endothelium-associated' substances in isolated human hand veins and arteries. Acetylcholine induced a large relaxation (Emax = 97 +/- 1%) in precontracted hand arteries. The relaxation was abolished by endothelial removal. In hand veins, acetylcholine induced a small relaxation (Emax = 13 +/- 4%), which was unaffected by endothelial removal. An endothelium-dependent relaxation was, however, obtained with high concentrations (greater than or equal to 10(-6) mol l-1) of the Ca2+ ionophore A23187. Contractile responses to noradrenaline, serotonin and prostaglandin F2 alpha did not differ between vein segments with and without endothelium. Endothelin was a potent constrictor of both veins and arteries. The potency and maximum response did not differ between the two types of vessel. Indomethacin pretreatment of veins did not influence the endothelin-induced contractions, suggesting that cyclo-oxygenase products are not involved in the response. In endothelin-contracted veins and arteries, the prostacyclin analogue iloprost elicited relaxation of similar potency and amplitude. The maximum relaxation in veins was, however, 3 times larger than that produced by prostacyclin itself. Platelet-activating factor was devoid of contractile and relaxant effects in both veins and arteries. The present study indicates differences between human hand veins and arteries regarding endothelial-dependent relaxation, and suggests that the modulatory role of endothelium-derived relaxing factor(s) is small in hand veins. The contractile and relaxant effects of endothelin and iloprost, however, did not differ between veins and arteries.

Sensory disturbances after two-portal endoscopic carpal tunnel release: a preliminary report.

Very few complications following endoscopic carpal tunnel release have been reported. We studied the incidence and pattern of sensory disturbances in 53 consecutive cases in which the Chow two-portal technique was used. Persistent sensory disturbances for 4 months or more were noted in six hands. Sensory tests were normal or near normal in all except one case. The disturbance was described by the patients as an uncomfortable tingling sensation or hyperesthesia, and in all cases the ring finger, especially the radial half, was involved. We wish to direct attention to this potential complication and suggest possible mechanisms behind it.

Contractile effects of noradrenaline and 5-hydroxytryptamine in human hand veins: a pharmacological receptor characterization.

The postjunctional receptors mediating contractile responses to noradrenaline (NA) and 5-hydroxytryptamine (5-HT) were characterized in ring segments of human hand veins by using subtype selective agonists and antagonists. The mechanical characteristics of the preparations were also examined by length-tension measurements. The length-active wall tension curve was bell-shaped and reached a maximum at a length corresponding to a passive distending pressure of approximately 14 mmHg. (-)-Phenylephrine consistently contracted the veins and was 24 times less potent than (+/-)-NA whereas clonidine produced a contraction in only two out of 11 vessel segments. Neither prazosin nor rauwolscine competitively inhibited the contractile response to NA, and large inter-individual differences were found in the degree of inhibition produced by the antagonists. However, application of both prazosin and rauwolscine almost abolished the NA-induced contraction. Ketanserin and methergoline inhibited the contractile response to 5-HT; the former in an apparently competitive manner with a pA2 value of 8.94, whereas the latter substantially reduced the maximum 5-HT response. It is suggested that NA elicits contraction in human hand veins by acting at a mixed population of alpha 1- and alpha 2-adrenoreceptors. The contractile response to 5-HT, on the other hand, appears to be mediated predominantly by 5-HT2 receptors.

Actions of some vasodilators on isolated human hand veins.

Vasospasm is a well recognized complication during microvascular surgery of the hand. In the search for new spasmolytic drug therapies, the effects of papaverine, nitroprusside, nimodipine and lidocaine on isolated human hand veins contracted by several postulated mediators of vasospasm were examined. Mechanical activity was recorded isometrically in ring segments of the vessels. Potassium ions, noradrenaline (NA), 5-hydroxytryptamine (5-HT) and prostaglandin F2 alpha (PGF2 alpha) all produced strong contractions that were highly dependent on the presence of extracellular Ca2+. Papaverine acted as a nonselective vasodilator, as it produced an almost identical inhibition of contractile responses to all examined stimulants. Nitroprusside inhibited contractions induced by agonists more than those evoked by K+, whereas the opposite was found for nimodipine. Nitroprusside also seemed to display a certain degree of selectivity among the agonist-induced responses (NA greater than PGF2 alpha greater than 5-HT). Lidocaine increased the contractile response to K+ and at high concentrations (greater than 10(-5) M) produced a contraction per se. The clinical efficacy of lidocaine as a vasodilator after topical application therefore seems to reflect an inhibitory action on vasoconstrictor nerves. Papaverine, nitroprusside, nimodipine and lidocaine differ considerably in their profiles of action and therefore deserve to be further evaluated in the treatment of vasospasm during microvascular surgery.

Influence of temperature and extracellular pH on contractile responses in isolated human hand veins.

The effects of moderate cooling and extracellular pH changes on concentration-response relationships for noradrenaline (NA), 5-hydroxytryptamine (5-HT) and prostaglandin F2 alpha (PGF2 alpha) were investigated in isolated human hand veins. pH changes were achieved by altering the NaHCO3 content of the Krebs solution. Cooling to 24 degrees reduced the maximum contractile responses to K+ (124 mM), NA and PGF2 alpha by 20-30%, whereas that to 5-HT was unchanged. The NA and 5-HT potencies were increased 8-10 times, whereas the PGF2 alpha potency was unaffected. A shift from alkalotic (pH 7.6) to acidotic (pH 6.9) conditions did not influence the contractile response to 124 mM K+, whereas the responses to NA, 5-HT and PGF2 alpha were inhibited with regard to both potency and maximum contraction. When related to neutral pH, acidosis significantly reduced only the 5-HT potency (4 times), whereas alkalosis selectively increased the NA and PGF2 alpha potencies (3 times). In the presence of prazosin (10(-7) M) cooling to 24 degrees significantly increased the NA potency, whereas no such increase was seen in the presence of rauwolscine (10(-7) M). Alkalosis significantly increased the NA potency in the presence of either antagonist. In conclusion, temperature and extracellular pH influenced the contractile responses to NA, 5-HT and PGF2 alpha in a differentiated manner. Alkalosis appeared to increase the response to both alpha 1- and alpha 2-adrenoceptor stimulation, whereas cooling preferentially increased that to alpha 2-adrenoceptor stimulation.

Characterization of contraction-mediating prostanoid receptors in human hand veins: effects of the thromboxane receptor antagonists BM13,505 and AH23848.

The effects of prostaglandin F2 alpha, prostaglandin E1, prostaglandin E2 and the thromboxane A2 analogue U46619 were determined in ring segments of human hand veins. All prostanoids except prostaglandin E1 elicited contraction. The order of potency was U46619 greater than prostaglandin F2 alpha greater than prostaglandin E2. The thromboxane receptor antagonists BM13,505 and AH23848 both caused a parallel rightward displacement of the concentration-response curve for U46619 without depression of the maximum contraction, suggesting competitive antagonism. Schild plots for both antagonists yielded regression lines with slope indices not significantly different from unity. The pA2 values for BM13,505 and AH23848 were 7.9 and 8.4 respectively. Both antagonists also effectively inhibited prostaglandin F2 alpha-induced contractions. However, AH23848 significantly reduced the maximum response, and the results with BM13,505 gave no clear indication of the type of inhibition. In vein segments submaximally contracted by 5-hydroxytryptamine, prostaglandins E1 and E2 produced a biphasic response with a relaxation at low and a contraction at high concentrations. Prostaglandin F2 alpha and U46619 failed to elicit relaxation under these conditions. However, in the presence of either thromboxane receptor antagonist, prostaglandin F2 alpha but not U46619 produced a relaxation. The results are compatible with the presence of at least two prostanoid receptors in human hand veins, a contraction-mediating thromboxane receptor and an as yet unclassified receptor eliciting relaxation. U46619 was a potent agonist at the thromboxane receptor and prostaglandin E1 and E2 preferentially stimulated the relaxation-mediating receptor, whereas prostaglandin F2 alpha appeared to be active at both receptor sites.

Endothelium dependence of prostanoid-induced relaxation in human hand veins.

The endothelium dependence of prostanoid-induced relaxation was examined in human isolated hand veins precontracted by endothelin. Indomethacin (10(-6) mol l-1) and the thromboxane A2-receptor antagonist BM 13.505 (10(-6) mol l-1) were present throughout. The endothelium was removed by insufflating carbogen through the vessel lumen. Prostaglandin (PG) F2 alpha, PGE1, PGE2, and prostacyclin (PGI2) elicited concentration-dependent relaxant effects. Removal of the endothelium reduced the relaxation induced by PGF2 alpha and PGE2, but not that elicited by PGE1 and PGI2. The order of potency was PGE2 approximately PGE1 approximately PGI2 > PGF2 alpha regardless of the presence or absence of endothelium. The relaxation elicited by an acidified solution of NaNO2 (generating nitric oxide) was almost identical in intact and endothelium-denuded vein segments. The results are compatible with the existence of two prostanoid receptor populations mediating relaxation: (1) one located on the smooth muscle cells and; (2) another present on the endothelium or possibly on the smooth muscle and modulated by the endothelium. The latter receptor appears to be activated by PGF2 alpha and PGE2, but not by PGE1 and PGI2.

Effects of nimodipine, Bay K 8644 and pinacidil on alpha 1- and alpha 2-adrenoceptor-mediated vasoconstriction in human hand veins.

The effects of nimodipine, Bay K 8644 and pinacidil, three drugs interfering with transmembrane Ca2+ fluxes in different ways, were investigated in isolated human hand veins. Their ability to influence the concentration-response relationship for noradrenaline (NA) was assessed in the absence and presence of prazosin or rauwolscine. The contractile response to NA was almost abolished in Ca2+ -free medium. Nimodipine and pinacidil depressed the NA concentration-response curve both in the absence and presence of alpha-adrenoceptor blockers. The NA response was only partially inhibited by nimodipine, indicating that NA may activate nimodipine-insensitive influx pathways, presumably receptor-operated calcium channels. Pinacidil inhibited the contractile response to 124 mM K+ and reduced the NA-induced contraction in the presence of nimodipine, suggesting that pinacidil has actions other than the opening of potassium channels and subsequent membrane hyperpolarization. Bay K 8644 increased the NA potency fourfold in the presence of rauwolscine, whereas it had no effect on the NA response in the presence of prazosin and in the absence of alpha-adrenoceptor blockade. Such an action of Bay K 8644 can be reconciled with alpha 1-adrenoceptor activation causing membrane depolarization and opening of potential-operated calcium channels. It may be concluded that both alpha 1- and alpha 2-adrenoceptor-mediated contractions in human hand veins are highly dependent on Ca2+ influx, although the mechanisms utilized to bring about this influx partly differ between the two receptor subtypes.