Disintegrin and metalloproteinases (ADAMs) expression in gastroesophageal reflux disease and in esophageal adenocarcinoma

Background. Clinically useful marker molecules for the progression of gastroesophageal reflux disease and Barrett’s esophagus (BE) to esophageal adenocarcinoma (EAC) are lacking. Many adenocarcinomas and inflammatory conditions exhibit increased expression of ADAMs, ‘a disintegrin and metalloproteinases’. Methods. We assessed the expression of five ADAMs (9, 10, 12, 17, 19) in three esophageal cell lines (Het-1A, OE19, OE33) by RT-PCR and Western blotting, and in human samples of normal esophagus, esophagitis, BE, Barrett’s dysplasia, and EAC by RT-PCR, and in selected samples by immunohistochemistry. Results. EAC patients showed increased mRNA expression of ADAMs 9, 12, 17 and 19, as compared to controls. At immunohistochemistry, ADAM9 and ADAM10 proteins were increased in EAC. Patient samples also showed increased mRNA expression of ADAM12 in esophagitis, of ADAM9 in BE, and of ADAMs 9, 12 and 19 in Barrett’s dysplasia, as compared to controls. Two EAC cell lines showed increased ADAM9 mRNA. Conclusions. ADAM9 expression is increased in EAC. Its predecessors show increased ADAM9 mRNA expression. The importance of the alterations in ADAM expression for the development of EAC, and their use as marker molecules, warrant further studies (AU)

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Disintegrin and metalloproteinases (ADAMs) expression in gastroesophageal reflux disease and in esophageal adenocarcinoma.

BACKGROUND: Clinically useful marker molecules for the progression of gastroesophageal reflux disease and Barrett's esophagus (BE) to esophageal adenocarcinoma (EAC) are lacking. Many adenocarcinomas and inflammatory conditions exhibit increased expression of ADAMs, 'a disintegrin and metalloproteinases'. METHODS: We assessed the expression of five ADAMs (9, 10, 12, 17, 19) in three esophageal cell lines (Het-1A, OE19, OE33) by RT-PCR and Western blotting, and in human samples of normal esophagus, esophagitis, BE, Barrett's dysplasia, and EAC by RT-PCR, and in selected samples by immunohistochemistry. RESULTS: EAC patients showed increased mRNA expression of ADAMs 9, 12, 17 and 19, as compared to controls. At immunohistochemistry, ADAM9 and ADAM10 proteins were increased in EAC. Patient samples also showed increased mRNA expression of ADAM12 in esophagitis, of ADAM9 in BE, and of ADAMs 9, 12 and 19 in Barrett's dysplasia, as compared to controls. Two EAC cell lines showed increased ADAM9 mRNA. CONCLUSIONS: ADAM9 expression is increased in EAC. Its predecessors show increased ADAM9 mRNA expression. The importance of the alterations in ADAM expression for the development of EAC, and their use as marker molecules, warrant further studies.

Coralline hydroxyapatite reinforced with polylactide fibres in lumbar interbody implantation.

Porous hydroxyapatite HA blocks reinforced with poly-l/dl-lactide fibres were used to maintain the lumbar disc space and to start to create intercorporeal fusion in 23 growing pigs. In four pigs two emptied non adjacent disc spaces were left open. After 3, 6, 12 and 16 weeks the implanted disc blocks were studied radiologically, histologically, histomorphometrically, microradiographically, and with oxytetracycline fluorescence. In plain films slight to moderate ossification of the implanted disc spaces was detected at 12 and 16 weeks. Resorption of the implants was seen radiologically from 3 weeks and fragmentation from 12 weeks onwards. In microradiographs disintegration of the coralline inner structure started at 3 weeks. Histologically, connective tissue ingrowth was seen inside the porous structure from three weeks onwards. Small amounts of new bone were visible and connective tissue inside the implant increased from a mean of 65.6% at 3 weeks to a mean of 79.4% at 16 weeks histomorphometrically. The bone ingrowth varied from 0.7 to 1.7%. A loss of height in the implanted disc spaces was seen (p < 0.05, linear regression analysis). In control pigs the emptied disc spaces lost their height similarly. The implants used were not strong enough to maintain the lumbar disc height.

Bioabsorbable fixation in orthopaedic surgery and traumatology.

Bioabsorbable internal fixation devices were introduced clinically in the treatment of fractures and osteotomies of the extremities at the Department of Orthopaedics and Traumatology, Helsinki University, in 1984. Since November 5, 1984, a total of 3200 patients were managed using bone or ligament fixation devices made of self-reinforced (matrix and fibres of the same polymer) bioabsorbable alpha-hydroxy polyesters. The devices used included cylindrical rods, screws, tacks, plugs, arrows, and wires. The most common indication for the use of bioabsorbable implants was the displaced malleolar fracture of the ankle. Transphyseal fixation with small-diameter, mainly polyglycolide pins was used in children. The postoperative clinical course was uneventful in more than 90% of the patients. The complications included bacterial wound infection in 4% and failure of fixation in 4%. In one-fifth of the latter cases, however, re-operation was not necessary. The occurrence of non-infectious foreign-body reactions two to three months postoperatively has been observed in 2% of the patients operated in the last few years with polyglycolide implants but none of the patients managed with polylactide implants. This inflammatory tissue response often required aspiration with a needle but did not influence the functional or radiologic result of the treatment. Owing to the biodegradability of these internal fixation devices, implant removal procedures were avoided. This results in financial benefits and psychological advantages. Bioabsorbable implants can also be used in open fractures and infection operations.

Clindamycin versus cloxacillin in the treatment of 240 open fractures. A randomized prospective study.

BACKGROUND AND AIMS: Systemic administration of antibiotics is recommended and has proved to lower infection rates in open fractures. However, no antibiotic has proved to be superior to any other. MATERIAL AND METHODS: In a prospective study 227 patients with 240 open fractures were randomized to receive either clindamycin or cloxacillin for infection prevention. RESULTS: The overall infection rate was 15%. Infection occurred in 9.3% of the clindamycin treated and in 20% of the cloxacillin treated fractures (p < 0.05). In the Gustillo Type I and II open fractures all the pathogens causing infection were gram-positive, while in the Type III open fractures 21 pathogens (57%) were gram-positive and 16 (43%) gram-negative. In the clindamycin treated fractures the infection rates in Type I and II open fractures were 3.3 and 1.8%, respectively, while in the cloxacillin group they were 20 and 3.8%, respectively. Both clindamycin and cloxacillin showed low effectiveness in the treatment of Type III open fractures, the highest infection rates being 75 and 67%, respectively (Type III B). CONCLUSIONS: Clindamycin provides good antimicrobic coverage against the most common pathogens causing Type I and II open fracture infections. In the treatment of Type III open fractures additional administration of an antibiotic with good gram-negative coverage is recommended.

Comparison of the fixation of subcapital femoral neck osteotomies with absorbable self-reinforced poly-L-lactide lag-screws or metallic screws in sheep.

Seven subcapital femoral osteotomies of adult sheep were each fixed with two absorbable self-reinforced poly-L-lactide lag-screws, and seven other osteotomies were each fixed with two metallic cancellous bone screws. At 3 and 12 weeks, radiographs were taken and callus formation, displacement, and union were evaluated. At 12 weeks, the animals were killed and strength measurements were carried out. According to the radiographs, union was achieved in six of seven osteotomies in both groups, while after 3 weeks one fixation in both the group treated with absorbable screws and the group treated with metallic screws had failed. There were no statistical differences between the groups with respect to callus formation or displacement. Regarding the strength of the osteotomized bones, at 12 weeks there were no statistically significant differences in the load-carrying capacity between the bones fixed with self-reinforced poly-L-lactide screws and those fixed with metallic screws. These results showed that self-reinforced poly-L-lactide screws, which have been used successfully in fractures and osteotomies in cancellous bone, are strong enough to support this more demanding fixation of weight-bearing bones.

Absorbable devices in the fixation of fractures.

Totally absorbable internal fracture fixation devices were introduced clinically in the treatment of fractures and osteotomies of the extremities at our department in 1984. A total of 2,500 patients were managed using bone or ligament fixation devices made of self-reinforced (matrix and fibers of same polymer) absorbable alpha-hydroxy polyesters between November 5, 1984, and January 12, 1994. The devices used included cylindrical rods or pins, screws, tacks, plugs, and wires. The most common indication for the use of absorbable implants was displaced malleolar fracture of the ankle. Transphyseal fixation with small-diameter polyglycolide pins was used in children. The postoperative clinical course was uneventful in over 90% of the patients. The complications included bacterial wound infection in 3.6% and failure of fixation in 3.7%. In one-fifth of these cases, however, reoperation was not necessary. The occurrence of noninfectious foreign-body reactions 2 to 3 months postoperatively has been observed in 2.3% of the patients operated in the last years with polyglcolide implants but in none of the patients with polylactide implants. This inflammatory tissue response often required aspiration with a needle or small incision but did not influence the ultimate functional or radiologic result of treatment. Owing to the biodegradability of these internal fixation devices, over 1,000 implant removal procedures were avoided during the 9-year period under review, allowing medical personnel at these facilities to focus on other procedures. Avoidance of removal procedures results in financial benefits and psychological advantages. The benefits of absorbable implants for war surgery are the same as for civilian life. Absorbable implants can also be used in open fractures and infection operations.

The effect of osteotomy and osteosynthesis in the mandibular condyle. A radiologic and histologic study in sheep.

Eighteen oblique osteotomies in sheep mandibular condylar necks were fixed with self-reinforced poly-L-lactide (SR-PLLA) (n = 9) or stainless steel (n = 9) screws (core diameters 2.4, 2.7, 3.0, or 3.5 mm). No intermaxillary fixation (IMF) was applied. The follow-up periods were 6, 12, and 24 weeks, respectively, after which the sheep were killed, and the status of the condylar head was assessed radiographically and histologically. The results showed that the fixation had been adequate. Bony destruction, osteophytes, and flattening of the condylar head, however, were frequently observed in both groups, as compared with the unoperated contralateral condyle. Histologic studies revealed that the thickness of the condylar head cartilage had increased and that the boundaries of the different cell layers were irregular, as was the junction of cartilage and bone. The diameter of the screw did not seem to have any influence on the occurrence of either radiologic or histologic signs of condylar degeneration. These findings indicate that screw fixation of condylar fractures in the mandible without IMF might result in degenerative joint disease.

Mechanical properties of biodegradable poly-L-lactide ligament augmentation device in experimental anterior cruciate ligament reconstruction.

The mechanical properties, including maximum load, elongation, and axial rigidity, of the biodegradable poly-L-lactic acid (PLLA) ligament augmentation device were investigated, 6, 12, 24, and 48 weeks after experimental anterior cruciate ligament (ACL) repair in 32 sheep. In 16 sheep the cut ACL was removed and reconstructed with the fascia lata augmented with a braided PLLA implant 3.2 mm in diameter. In 16 sheep the ACL was cut from its midportion, sutured, and then augmented with a PLLA implant. The contralateral knee served as a control. At 6 weeks the maximum loads of the reconstructed ACL in the fascia lata-PLLA and primary suture-PLLA groups were 9% and 6%, respectively, of the contralateral ACL, but they increased with time and at 48 weeks were 21% and 12%, respectively, of the control. In the fascia lata-PLLA group the increase in maximum load was evident (P < 0.05) during the follow-up period. During the first 12 weeks the axial rigidity (expressing the elasticity of the reconstruction) was poor, especially in the high-stress region corresponding to the tensile load close to the maximum load. Thereafter the axial rigidity increased, being 48% of the control in the fascia lata-PLLA group and 29% in the primary suture-PLLA group at 48 weeks. In the low-stress region between 10 N and 100 N the increase in axial rigidity in the fascia lata-PLLA group was apparent (P < 0.05) throughout the follow-up, with values of 72% of the control in the fascia lata-PLLA and 47% in the primary suture-PLLA group at 48 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)

Fixation of subcapital femoral osteotomies by poly-L-lactic acid pins. An experimental study in sheep.

In an experimental study in nine sheep, self-reinforced poly-L-lactic pins were used to fix subcapital femoral osteotomies. One out of three was consolidated at 3 weeks. At 6 weeks, one out of 3 had failed, and the other two were united by bone. At 12 weeks all the osteotomies had healed. These results showed that absorbable SR-PLLA pins could be used to fix this type of osteotomy.

Comparison of absorbable self-reinforced multilayer poly-l-lactide and metallic plates for the fixation of mandibular body osteotomies: an experimental study in sheep.

Eighteen unfavorable transverse osteotomies were created in the mandibular body of sheep. Nine were fixed with self-reinforced poly-l-lactide and nine with metallic dynamic compression plates. Both plates were fixed with similar titanium screws. The follow-up times for radiographic, histologic, and microradiographic studies were 6, 12, and 24 weeks. With both methods, bony union with callus formation was accomplished by 6 weeks in all but one osteotomy in the metallic fixation group. There were no signs of plate failure.

Intramedullary fixation of cortical bone osteotomies with self-reinforced polylactic rods in rabbits.

Osteotomies of the femoral shaft in rabbits were fixed with intramedullary rods made of poly-L-lactic acid (SR-PLLA) and poly-DL/L-lactic acid (SR-PDLLA/PLLA). Follow up was from one week to 2 years. In the PLLA group, in 37 out of 40 osteotomies the fixation was firm and the bone was united. In the PDLLA/PLLA group, the fixation was firm in 30 out of 45, but in 13 of these angular deformity of more than 10 degrees had occurred. The fixation had failed in 15. No inflammatory or foreign body reaction was seen in either group. This study demonstrates that SR-PLLA rods are suitable fixation for cortical osteotomies in rabbits.

Mechanical properties of biodegradable ligament augmentation device of poly(L-lactide) in vitro and in vivo.

To evaluate the mechanical properties of absorbable braided poly(L-lactide) (PLLA) fibre implants, 2.0 and 3.2 mm in diameter, maximum load defined as tensile load carrying capacity, elongation and axial rigidity were investigated after immersion in phosphate-buffered distilled water at 37 degrees C and pH 6.1 and after subcutaneous implantation in rabbit. The results confirm earlier indications that PLLA degrades faster in vivo than in vitro. The non-sterilized 2.0 mm implants lost 69% of initial tensile load carrying capacity in 46 wk in vitro. In vivo the loss of tensile load carrying capacity of the 2.0 and 3.2 mm implants was most marked between 6 to 12 wk. After 48 wk in vivo 2.0 and 3.2 mm implants retained 3 and 4% of initial tensile load carrying capacity respectively. Both in vitro and in vivo, elongation diminished in the same way as the maximum load. In vitro, mean axial rigidity of unsterilized 2.0 mm implants was 64 N during the first 34 wk but fell to 31 N at 46 wk. In vivo the initial mean axial rigidity of the 2.0 and 3.2 mm implants was 29 and 95 N respectively. At 24 wk the mean axial rigidity was 2 N in both implants.

[Absorbable rods and screws: a new method of fixation for fractures of the olecranon]. / Broches et vis biorésorbables: une nouvelle méthode de fixation des fractures de l'olécrâne. Etude clinique prospective sur 41 malades.

Between April 1986 and July 1990 fractures of the olecranon in 41 adult patients were treated by fixation with absorbable rods (20 patients) and screws (21 patients) of self-reinforced polyglycolide (SR-PGA), 3.2 mm in diameter and 20-70 mm in length. Patients were followed up for a mean time of 2 years 7 months (range 1 year to 4 years 6 months). After reduction of the fracture, channels were drilled from the proximal fragment through the cortex of the distal fragment and the fractures were fixed with absorbable rods or screws. By one year from follow-up maintenance of an anatomical reduction of the fracture was seen in 34 patients. Failure of fixation requiring a second operation occurred in 2 cases. In all cases functional recovery was at least satisfactory. Sinus formation as a sign of transient tissue reaction was observed in 3 cases, but did not influence the healing of the fractures or the functional recovery. The results in patients treated with rods or screws was similar. Absorbable screws combined with small rods and absorbable sutures allow treatment of +ore severe fractures of the olecranon than do rods alone.

Self-reinforced absorbable screws in the fixation of displaced ankle fractures: a prospective clinical study of 152 patients.

The series consisted of 152 patients with ankle fractures treated between May 1987 and August 1989 using absorbable screws of self-reinforced polyglycolide 3.4 mm in inner diameter and 25-70 mm in length. The mean follow-up time was 2 years, 5 months (range, 1 year, 7 months-3 years, 10 months). After open reduction, a channel was drilled through the fracture surfaces and the fragments were fixed with one absorbable screw or screws. A plaster cast was used postoperatively. At 1-year follow-up observation, the radiographical result was anatomical in 93.3% of 104 patients with unimalleolar and bimalleolar ankle fractures (Weber A or B) and in 80.5% of 41 severe ankle fractures. Seven patients were unavailable for follow-up observation. Two reoperations were performed because of primary or secondary failure of fixation. In all unimalleolar and bimalleolar fractures and in 95.1% of severe ankle fractures the functional recovery score was at least satisfactory. Sinus formation as a sign of tissue reaction was observed in 10 patients 2-6 months postoperatively, but this did not influence the healing of the fracture or the functional recovery. This report is the first extensive publication on the clinical use of absorbable screws.

New generation biodegradable plate for fracture fixation: comparison of bending strengths of mandibular osteotomies fixed with absorbable self-reinforced multi-layer poly-l-lactide plates and metallic plates--an experimental study in sheep.

Eighteen osteotomies of sheep's mandibular corpus were fixed: nine with self-reinforced multi-layer poly-l-lactide (SR-PLLA) plates and nine with metallic plates. Both plates were fixed with similar metallic screws. The right corpus of each sheep acted as a control. Radiographic analysis was carried out at 3 weeks and at sacrifice (6, 12 or 24 weeks) when the bending force needed to break the osteotomy site was measured. At 6 and 12 weeks of follow-up the osteotomy fixed with the PLA-plate seemed to tolerate the bending force better but no significant differences were detected at 3 or 24 weeks. The results have been satisfactory and have led the authors to continue with the development of a SR-PLLA plate-and-screw device for fracture fixation.

Preliminary study of porous hydroxylapatite particle containment with a curved biodegradable implant in the sheep mandible.

A conventional augmentation method without a splint was compared with the use of a biodegradable polyglycolide (PGA) splint as a container of hydroxylapatite (HA) particles. With the PGA splint there was a 35% rate of dehiscence of the incision, leading to loss of HA particles. Based on microradiographic measurements, the HA was retained better on the side augmented by the conventional technique. Toward the end of 24 weeks, however, a decrease of augmentation and in the quantity of HA was seen with both methods. According to the histologic studies, there was evidence of HA phagocytosis by osteoclast-type cells. In the histomorphometric studies after 24 weeks of follow-up, new bone ingrowth was 12% without and 10% with the PGA splint. Although the planimetric studies showed the PGA splint to be a good container, the material still requires further development.

Absorption, biocompatibility, and fixation properties of polylactic acid in bone tissue: an experimental study in rats.

The absorption, biocompatibility, and fixation properties of self-reinforced (SR) poly-L-lactic acid (PLLA) and poly-DL-lactic acid (PDLLA) were investigated in cancellous bone in 56 rats. Osteotomies of the distal femur were operatively fixed with cylindrical implants made of SR-PLLA and SR-PDLLA/PLLA (40 PDLLA:60 PLLA). The follow-up times were one, three, six, 12, 24, 36, and 48 weeks. Roentgenographic, microradiographic, histologic, histomorphometric, and oxytetracycline-labeling studies were done. Histologically, there was no evidence of inflammation or foreign-body reaction in the bony tissues. Histomorphometric analysis showed that absorption in the SR-PDLLA/PLLA implant was faster than in the SR-PLLA implant. Absorption started peripherally in the implants and continued with subsequent replacement by new bone. At 48 weeks the implant was completely surrounded by a layer of new bone. The SR-PLLA and SR-PDLLA/PLLA implants were visible in all specimens during the 48-week follow-up period. Ninety-five percent of the osteotomies were consolidated. Implants made of SR polylactic acid in rats proved to be biocompatible and slowly absorbable, and they possessed sufficient mechanical properties for fixation of osteotomies.

Chevron osteotomy fixed with absorbable polyglycolide pins.

Seventy-eight chevron osteotomies augmented by internal fixation with self-reinforced polyglycolide pins, 2 mm in diameter, were performed in 60 patients suffering from a painful hallux valgus. The mean metatarsophalangeal angle was 31 degrees, and there was a metatarsus primus varus varying from 10 degrees to 20 degrees. The average follow-up time was 14 (range, 12 to 31) months. No postoperative redisplacement or disturbance of healing of the osteotomy was observed, but recurrence of hallux valgus occurred in 8 feet (10%), each initially with a moderate to severe hallux valgus. Some pain at the first metatarsophalangeal joint during physical activity remained in 12 feet (15%). There was a mean shortening of 2.5 mm of the first metatarsal bone, and the most significant shortening was associated with pain in the forefoot. The metatarsophalangeal joint motion was not decreased. The subjective overall result was excellent or good in 75% of the patients. Because of the biodegradability of the implants used, no secondary procedures to remove the implants were necessary.

Four-year outcome of operative treatment of acute acromioclavicular dislocation.

Seventy of 100 consecutive randomly allocated patients who had been treated for acute total acromioclavicular dislocation with either transfixation with two smooth Kirschner wires (29 cases), two threaded Kirschner wires (20), or one ASIF cortical screw (21) were followed for an average of 4 years. The coracoclavicular ligaments were not sutured. Results were good in 67 of the 70 patients. Using stress radiographs, no redislocation was found in 56 cases. Two complete dislocations were found in patients who had been treated with screw fixation. Osteolysis of the lateral head of the clavicle was found in 13 patients, eight of whom had been treated with screw fixation (p less than 0.01). Our results speak for the use of threaded Kirschner wire fixation for the operative treatment of acute total acromioclavicular dislocation.