Unfavourable short-term outcomes of a poly-L/D-lactide scaffold for thumb trapeziometacarpal arthroplasty.

The bioabsorbable poly-L-D-lactide joint scaffold arthroplasty is a recent attempt in the reconstruction of small joints in rheumatoid patients. In this study, we analysed the 1-year clinical, functional and radiologic results of partial trapeziectomy with the poly-L-D-lactide (96/4) joint scaffold in 23 patients with isolated trapeziometacarpal osteoarthritis. The results showed that the procedure provided pain relief and improvement in overall function according to the Quick Disabilities of the Arm, Shoulder and Hand score in most patients. However, radiographs demonstrated a high frequency of osteolysis around the implant. Seven patients developed clinically manifested foreign-body reactions 6 months to 1 year after surgery. The reason for the unexpected tissue reactions may relate to excessive mechanical cyclic loading of the implant. The outcomes of this implant in our patients have not been sufficiently beneficial and we have discontinued use of this implant in isolated trapeziometacarpal osteoarthritis.

Use of bioabsorbable osteofixation devices in the hand.

Bioabsorbable internal fixation by means of pins, tacks, screws and miniplates offers an alternative to metallic osteofixation for the stabilization of small bone fractures, osteotomies, ligament injuries and fusions in the hand. The advantages of using them include avoidance of metallic-implant-related long-term complications and a secondary removal operation. Currently the most commonly used devices are made of poly L-lactide (PLLA) and copolymers of polylactides (P(L/DL)LA) and polyglycolide (PLGA). In areas of mechanical stress, the use of ultra-high-strength self-reinforced devices is recommended. Biomechanical studies on fresh frozen bones have shown that the fixation rigidity achieved with self-reinforced devices approaches that of metallic osteofixation methods. The reliability of modern implants has been confirmed in several experimental and clinical studies.

The influence of chemical sympathectomy on pain responsivity and alpha 2-adrenergic antinociception in neuropathic animals.

We studied the effect of chemical sympathectomy by 6-hydroxydopamine (6-OHDA) on pain behavior and alpha(2)-adrenergic antinociception in rats with a spinal nerve ligation-induced neuropathy. For assessment of alpha(2)-adrenergic antinociception, the rats were treated systemically with two alpha(2)-adrenoceptor agonists, one of which only poorly (MPV-2426) and the other very well (dexmedetomidine) penetrates the blood-brain barrier. Moreover, the effect of MPV-2426 on spontaneous activity of dorsal root nerve fibers proximal to the nerve injury was determined. Systemic treatment with 6-OHDA produced a marked decrease in immunocytochemical labeling of sympathetic nerve fibers in the skin but it produced no marked change in basal pain sensitivity to mechanical stimulation either in neuropathic or sham-operated animals. Systemic administration of MPV-2426 and dexmedetomidine produced a dose-dependent tactile antiallodynic effect in neuropathic animals. Intraplantar injection of MPV-2426 had an identical antiallodynic effect independent of whether it was injected into the neuropathic or contralateral hindpaw. In a test of mechanical nociception and hyperalgesia, dexmedetomidine markedly attenuated pain responses in all experimental groups, whereas MPV-2426 had a weak but significant pain attenuating effect only in neuropathic animals. In the tail flick test, both alpha(2)-adrenoceptor agonists had a significant antinociceptive effect. The pain attenuating effect of MPV-2426 was enhanced by pretreatment with 6-OHDA, except in a test of tactile allodynia. MPV-2426-induced modulation of spontaneous activity was not a general property of dorsal root fibers proximal to the injury. The results indicate that a chemical destruction of sympathetic postganglionic nerve fibers innervating the skin does not markedly influence cutaneous pain sensitivity nor is it critical for the alpha(2)-adrenoceptor agonist-induced attenuation of pain behavior in neuropathic or non-neuropathic animals. Chemical sympathectomy, independent of neuropathy, enhanced the pain attenuating effect by MPV-2426, probably due to a peripheral action, whereas in non-sympathectomized control and neuropathic animals peripheral mechanisms have only a minor, if any, role in the alpha(2)-adrenoceptor agonist-induced antinociception.

Interleukin-6 in aseptic loosening of total hip replacement prostheses.

OBJECTIVE: To investigate the level of interleukin-6 (IL-6) expression in the synovial-like interface membrane (SLIM) and in the pseudosynovial tissue surrounding the artificial hip joints, as well as in the pseudosynovial fluid from aseptically loosened total hip replacement (THR) prostheses. METHODS: A series of methods were used in this study including immunohistochemical staining, double immunofluorescence labeling, enzyme-linked immunosorbent assay (ELISA), and reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: IL-6 was found in all SLIM and the pseudosynovial tissue samples from aseptic loosening of THR. Semi-quantitative morphometry showed that IL-6 containing cells were more numerous in the SLIM (911 +/- 197; p < 0.01) and the pseudosynovial tissue samples (883 +/- 310; p < 0.01) than in the control synovial tissue (291 +/- 184). Double labeling confirmed that macrophages and fibroblasts were the predominant cell types expressing IL-6. These findings were confirmed by RT-PCR. ELISA revealed no difference in the IL-6 concentration between the pseudosynovial fluid and the control synovial fluid obtained from the patients undergoing hip arthroscopy. CONCLUSIONS: IL-6 locally produced in SLIM may in a paracrine manner contribute to periprosthetic osteolysis of the nearby bone. In contrast, fluid phase IL-6 does not seem to contribute to this end.

Effects of low-dose, noncytotoxic, intraarticular liposomal clodronate on development of erosions and proteoglycan loss in established antigen-induced arthritis in rabbits.

OBJECTIVE: To assess the clinical and histologic effects of an intraarticular application of low-dose (non-cytotoxic) liposomal clodronate in established antigen-induced monarthritis (AIA) in rabbits. METHODS: AIA was monitored by assessments of joint swelling, C-reactive protein levels, and radiographic changes in 17 NZW rabbits for 8 weeks during the course of weekly intraarticular injections of liposomal clodronate (0.145 mg/injection, low dose) or "empty" liposomes. The contralateral knee was injected with liposome buffer alone as the control. End-point analyses included macroscopic joint examination, immuno- and TUNEL staining, Safranin O staining/microspectrophotometry, and tumor necrosis factor alpha (TNFalpha) convertase enzyme (TACE) inhibition assay. RESULTS: Liposomal clodronate-treated rabbits showed a reduction and delay in joint swelling during the first 3 injections. Expression of matrix-bound (solubilized) TNFalpha, lining cell hyperplasia, and levels of RAM-11+ macrophages were low in the synovium of the liposomal clodronate treatment group, but the proportion of apoptotic lining cells was not affected. The radiologic score was low at the end of weeks 2 and 4, but at 8 weeks, no difference, compared with controls, was found in pannus formation or in the extent of joint erosion; also, joint swelling was higher than before initiation of treatment. Injections of liposomal clodronate prevented cartilage proteoglycan loss, which was significant in the superficial zone only. TACE activity was not inhibited by clodronate. CONCLUSION: Liposomal clodronate had temporary antiinflammatory and antierosive effects on established AIA in rabbits. Over the long-term, the loss of cartilage proteoglycans was halted. This observed treatment effect may be related to the inhibition of TNFalpha production and processing in the synovium.

Developments in craniomaxillofacial surgery: use of self-reinforced bioabsorbable osteofixation devices.

Because of the problems associated with the conventional osteofixation devices used in craniomaxillofacial surgery, absorbable devices present an appealing alternative. Devices made of the polymers polylactide, polyglycolide, and their copolymers (PLGA and P[L/DL]LA) are currently the most commonly used. Ultrahigh-strength implants can be manufactured from these polymers with the self-reinforcing technique. Over the authors' almost two decades of study, both in experimental and clinical settings, self-reinforced devices have proved to be biocompatible, easy to handle, and mechanically strong, even for the fixation of femoral neck fractures. In craniomaxillofacial surgery, the authors have used self-reinforced devices for over 8 years without complications. Because of the more favored degradation characteristics, currently the copolymeric self-reinforced devices (P[L/DL]LA, Biosorb FX and PLGA, Biosorb PDX; Elite Performance Technologies, Solana Beach, Calif.) represent the advancing front in the application of absorbable devices in craniomaxillofacial surgery. The authors' share their experience and their studies of self-reinforced devices, which possess the highest strength and ductility of all bioabsorbable products.

Expression of epidermal growth factor and transforming growth factor alpha in interfacial membranes retrieved at revision total hip arthroplasty.

BACKGROUND: The interfacial membrane between bone and implant has been shown to be a key tissue in the process of aseptic loosening of total hip arthroplasty. The cells within the interfacial membrane produce numerous inflammatory mediators which, through complex mechanisms, cause periprosthetic osteolysis and aseptic loosening. Both epidermal growth factor (EGF) and transforming growth factor alpha (TGFalpha) have similar biological functions. They have been found to stimulate bone resorption. OBJECTIVE: To investigate the presence, cellular localisation, and extent of expression of EGF and TGFalpha in interfacial membrane retrieved from revision total hip arthroplasty and compare it with that in synovial membrane from primary total hip arthroplasty. METHODS: Ten interfacial membranes and 10 synovial membranes were stained with avidin-biotin-peroxidase complex for EGF and TGFalpha. The staining process was done using the Lab Vision Autostainer. The results were measured by a semiautomatic VIDAS image analysis system. RESULTS: Immunoreactivity for both EGF and TGFalpha was found in the endothelial cells of blood vessels, macrophages, and fibroblasts, both in interfacial membranes and synovial membranes. However, the number of EGF (980 (370)) and TGFalpha (1070 (360)) positive cells per mm(2) was greater in interfacial membranes than in the synovial membranes (220 (200), 270 (100); p<0.01). CONCLUSION: It is suggested that owing to their increased expression in interfacial membrane, EGF and TGFalpha may have an important pathogenetic role in stimulating periprosthetic bone resorption in aseptic loosening of total hip arthroplasty.

Transforming and epidermal growth factors in degenerated intervertebral discs.

We studied the presence of anabolic growth factors in human herniated intervertebral discs (IVD) using a reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry. Messenger RNA (mRNA) was isolated from the nucleus pulposus using oligo (dT)25 superparamagnetic beads and probing with gene-specific primers in RT-PCR. mRNA coding for TGF-alpha (3/10), EGF (0/10), TGF-beta1 (0/10) and TGF-beta3 (2/10) or the EGF receptor (EGF-R; 0/10) and TGF-beta type-II receptor (0/10) was found only occasionally. Beta-actin was always present and positive sample controls confirmed the validity of the RT-PCR assay. These RT-PCR findings were confirmed using immunohistochemical staining of EGF and TFG-beta, whereas TGF-alpha protein was always found associated with discocytes. We conclude that the nucleus pulposus of the herniated IVD is vulnerable to proteolytic degradation and depletion of proteoglycans due to the lack and/or low production of anabolic growth factors/receptors which could increase the local synthesis of the extracellular matrix.

Effect of the Choice of Primary Chemotherapy on the Cumulative Length of Stay in Hospital for Multiple Myeloma.

The actual use of hospital beds for patients with multiple myeloma was calculated from a randomised trial of primary treatment with either melphalan and prednisone (MP, 66 patients) or intensive combination chemotherapy with vincristine, cyclophosphamide, lomustine, melphalan and methylprednisolone (MOCCA, 64 patients). The survival of the patients was similar in both arms, and the samples, 20 and 32 patients, respectively, were well representative for the whole arms. The average numbers of hospital days were similar fur both arms. For the first year MP 33.2 (SD 27.6) vs. MOCCA 32.1 (SD 19.0), and during the first to 4th years 78.5 (SD 45.9) vs. 67.8 (SD 34.1). For the year of death it was 50.4 (SD 33.1) vii. 36.3 (SD 27.0), respectivelly. Thus the choice of primary chemotherapy whether conventional or more aggressive had no influence on the actual number of in-patient hospital days concerned. When the combination chemotherapy schedule is well tolerated it can be administered just as well on an ambulatory basis or by using it with very short admissions. It seems that the need for inpatient care for patients with multiple myeloma is mostly related to the complications of the disease itself and to intercurrent disorders including infections.

The Finnish leukaemia group: levamisole in maintenance therapy of acute myeloid leukemia in adults.

The Finnish Leukaemia Group has carried out a randomized, multicenter trial to study the effect of levamisole on the remission maintained with 6-mercaptopurine and methotrexate in acute myeloid leukaemia in adults. Levamisole was given on 3 consecutive days every 2 weeks. Twenty-five patients received only chemotherapy, while 26 patients received levamisole as well. The patients receiving levamisole showed significantly better remission duration than those given only chemotherapy (P = 0.033, Mantel's summary chi 2-text). There are four long term survivors in the levamisole group versus none in the chemotherapy group. The remissions have lasted 48-75 months.

Three cases of severe verapamil poisoning.

Three cases of verapamil intoxication are described. The first two patients took 6.4 g verapamil each and the third one took 0.8 g of verapamil and alcohol. All three developed a third-degree atrioventricular dissociation, the first patient developed a slow idioventricular rhythm without atrial activity, the second a temporary asystole. All were hypotensive, had anuria and shock, the first two were unconscious for several hours. The first one was treated with artificial cardiac pacing, orciprenaline and calcium gluconate, the second with cardiac pacing and orciprenaline. The third patient received fluids and a dopamine infusion. In the first case sinus rhythm returned 31 h after the swallowing of tablets, in the second after 32 hr and in the third after 10 h. Pacing with intensive monitoring and care seemed to be the most beneficial treatments in these cases.