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Biomedical subjects

O E Illi

Publications and source records attributed to O E Illi.

At least 19 recordsLinked to original sources

Stabilizing insulin-like growth factor-I in poly(D,L-lactide-co-glycolide) microspheres.

This study aimed at developing a controlled drug delivery system for recombinant human insulin-like growth factor-I (IGF-I) for localized delivery in bone healing. IGF-I was microencapsulated into an end-group uncapped 14 kDa poly(D,L-lactide-co-glycolide) 50:50 (PLGA 50:50) by solvent extraction from a W(1)/O/W(2) dispersion. Prior to encapsulation, IGF-I was exposed to ultrasonication in a water/dichloromethane dispersion, and its stability tested in the presence and absence of various excipients in the W(1) phase. HPLC and RIA were used for the assessment of IGF-I stability. Microencapsulated IGF-I was tested again for its structural intactness and also for in vitro release from various formulations containing appropriate co-encapsulated excipients. A specific fat cell assay was used to determine the biological activity of released IGF-I. Moderate ultrasonic treatment of aqueous IGF-I/dichloromethane mixtures caused approx. 50% IGF-I degradation. However, IGF-I was fully protected when bovine serum albumin, succinylated gelatin or poly(ethyleneglycol) were added to the aqueous IGF-I. Co-encapsulation of these excipients protected efficiently the protein upon microencapsulation. IGF-I release from microsphere formulations was sustained for up to 13 days featuring a moderately pulsatile pattern, depending on the microsphere composition. Typically, the amounts of IGF-I released within the first 24 h (burst) and during the second release pulse were in the order of 20 and 40%, respectively, of the total dose. The biological activity of released IGF-I was confirmed at selected time-points by the fat cell assay. In conclusion, the developed microspheres proved to be suitable to release biologically intact IGF-I over up to 13 days, a time-period considered to be relevant to promote bone fracture healing.

Adipocytes↗

First clinical evaluation of a new concept for puncture-site occlusion in interventional cardiology and angioplasty.

UNLABELLED: Percutaneous transluminal angioplasties of coronary and peripheral vessels are frequently used and replace open surgery in a certain percentage. Hemostasis in most of these patients is reduced or inhibited and often leads to hemorrhage from the puncture track. Due to this fact, hospitalization is not only mandatory, but also surgical revision of the puncture site is often required. We designed and produced a coaxial delivery system, which is mounted on the indwelling guide-wire after withdrawal of the instrumentation for angioplasty. The delivery system is advanced down to the outer wall of the punctured vessel and 1 cc of human two-compound fibrin glue is released. Based on our experience with laboratory and animal research, which we already presented at the 7th International Symposium on Pediatric Surgical Research in Heidelberg, May 27-28, 1994, we conducted the first trials in interventional cardiology. In 1996, a first group of 10 patients, aged 49 to 80 years, underwent sealing of the right femoral artery after diagnostic evaluation (n = 3) of coronary balloon dilatation (n = 7). In patients, the local manual compression time was less than 5 minutes and 1 patient needed 10 minutes of digital compression. In one case, bleeding continued and a compression bandage was successful, whereas in another case the local hematoma formation needed surgical revision with suture of the ruptured vessel wall. CONCLUSION: Puncture-track sealing with locally applied fibrin glue seems to be an efficient tool to avoid bleeding after interventions of coronary and peripheral vessels. In the meantime, the device has been improved by a target system to optimize the delivery of the glue exactly at the outer wall of the vessel.

Aged↗

Stimulation of fracture healing by local application of humoral factors integrated in biodegradable implants.

Growth stimulation by growth hormones or by IGF-1 is well known whereas publications about stimulation of fracture healing with these substances are rare. One of the main effects of IGF-1 is angiopoiesis which consequently may be expected to induce and accelerate the soft tissue callus formation. BMP-2 is a stimulator for osteoclasts and osteoblasts and prepares the osseous reparation. RhBMPs, mostly BMP-2, are already used in the reconstruction of the cranial vault. The main disadvantage of these proteins is the quick inactivation after about 20-30 minutes. Local stimulation without systemic effects might be avoided by releasing a low but constant dose of IGF-1 or BMP. We speculate that the combination of a reasonable implant with an integrated drug release system may enlarge the field of application of biodegradable implants in the treatment of fractures. Such an implant might remarkably reduce the time for fracture healing and also lower the costs of postoperative treatment. In this paper we report our animal models in which we have tested constructive principles of biodegradable implants, we present the first clinical experiences with polyactates (PLLA) in the osteosynthesis of children, and we describe our inventions concerning drug releasing implants. 1) PLLA-implants a) The animal models We performed on oblique osteotomy of the right metacarpal bone in 48 juvenile calves and osteoplastic reconstructions of the cranial vault in 28 juvenile Göttinger minipigs. Biodegradable osteosynthesis with PLLA implants led to results as good as with conventional materials in both animal models, so that we proceeded to clinical evaluation in children. b) The clinical application in children 35 children, aged 6 weeks to 17 years, had resorbable osteosynthesis of their cranioplasties for correction of congenital malformations and posttraumatic reconstructions. The follow-up ranged from 5-15 years. 2) Invention of a drug-releasing system IGF-1 or BMP-2 is planned to be incapsulated by evaporation technique into nanospheres of low PDLLA (Poly-DL-Lactite) with a molecular weight of about 20,000 and an expected resorption time of 2-3 weeks (patent pending). 3) Concept of our drug-releasing resorbable implants Plates could be built up in multilayers of PDLLA sheets, separated by a spongiform matrix containing the IGF-1- or BMP-2-loaded nanospheres. The screws are hollow due to an internal driving system. The specially designed thread could also contain nanospheres, which would be brought into the cortical bone and the medullary space. The cavity of the screw is filled up with nanospheres after tightening.

Absorbable Implants↗

Postrenal anuria after appendectomy in childhood.

An 11-year-old boy suffered from macroscopic haematuria and bilateral flank pain a few days after uneventful appendectomy for retrocaecal appendicitis phlegmonosa. Ultrasonography revealed a complete bilateral distal obstruction of the ureters. Renal failure due to postrenal anuria resolved completely after intravenous antibiotics.

Anuria↗

[Surgical diseases in the inguinal area in children].

This outline describes the diagnostic and prognostic factors as well as the operative procedures based on the experiences made at the University Clinic for Pediatric Surgery, Zurich. Focused on practical work, the most frequent congenital, acute and chronic affections are described with respect to differential diagnostic characteristics.

Child↗

Illi intracranial pressure monitoring and fixation device. A new fixation system for intracranial pressure monitoring in children and adolescents in paediatric neurotraumatology, hydrocephalus and craniofacial surgery.

Fixation and positioning of intracranial pressure (ICP) monitoring devices in small children with very thin skull bones pose serious problems. We present a new ICP fixation device with two movable components compressing the skull bone from in- and outside. This new fixation system, designed by PD Dr. O.E. Illi and licensed by White Spot AG, Surgical Tools and Research, Baar, Switzerland, guarantees far greater stability and reliability than conventional screws or bolts. It is fully compatible with a range of fiberoptic or pneumatic transducer systems. We have applied this new device successfully in 10 patients.

Adolescent↗

Achalasia in childhood and adolescence.

We analysed the charts of paediatric patients suffering from oesophageal disorders in 5 departments of paediatric surgery in Switzerland from 1972-1993 finding only 16 patients with proven achalasia (0.6%). The personal history showed a wide gap of several years from the first symptoms until diagnosis and treatment due to false interpretation of symptoms. Dilatations alone have never been definitely successful. In 16 patients, a Heller's procedure was done, 2 had an additional Thal, 12 a Nissen fundoplication, one a hiatoplasty and one no antireflux procedure. 3 patients needed further postoperative dilatations for several months up to 3 1/2 years. One patient suffering from an AAA syndrome (Achalasia/Alacrimia/ACTH deficiency) did not improve after Heller's procedure with Nissen fundoplication and dilatations. We finally had to resect the oesophagus and replace it by gastric transposition. Two children were lost for long-term follow-up. In 14 patients the follow-up is more than 10 years. 14 patients take normal food and are in the normal percentiles for length and height. Achalasia in childhood shows a wide spectrum of oesophageal dysmotility. In many cases, the propulsive force might be so weak that only a very lose antireflux procedure is tolerated. Occasionally, the whole oesophagus is without appropriate function and has finally to be resected as in our patient suffering from AAA syndrome. This child is now free of clinical pathological symptoms since several years.

Adolescent↗

Fractures about the knee: growth disturbances and problems of stability at long-term follow-up.

The aim of this study was to collect information about the incidence of leg-length discrepancy, axis deviation and instability resulting from fractures about the knee in childhood. We reviewed 43 patients with a clinical and radiological examination after a mean follow-up period of 13 years. The fractures were divided into four subgroups, each one presenting typical problems. Growth disturbance (shortening and axis deviation) making secondary procedures necessary was seen in 5 out of 14 (36%) distal femoral epiphyseal fractures. Complex instability was observed in 3 out of 7 (43%) proximal tibial epiphyseal fractures. In the tibial spine fractures anatomical reduction often did not prevent moderate cruciate ligament insufficiency; and in the metaphyseal fractures 2 of the 7 cases showed leg-lenghtening. In conclusion, the Salter classification seems to be of little prognostic value at the knee as Type-II fractures are frequently followed by asymmetric growth arrest. Open reduction is not reliable in avoiding this complication. Associated ligament injuries are not rare and deserve more attention.

Adolescent↗

Cranioplasties for congenital and acquired skull defects in children--comparison of new concepts with conventional methods.

From 1974 to 1992 fifty-two patients with congenital or acquired skull defects were operated at the Department of Pediatric Surgery of the University Children's Hospital of Zurich. By 1988, in 26 patients conventional methods with PMMA (polymethyl methacrylate) plasties or rib plasties were performed. After 1988, in 26 patients skull reconstruction was done by skull splitting, application of lyophilized bone or cartilage or a combination of both. In the latter period, stabilization and fixation was always provided by biodegradable screws and bands. The results of the different techniques were compared in a retrospective fashion. PMMA plasties provided immediately full stability and good cosmetic results. Another advantage was their availability. In one patient (= 4.8%), a wound infection required the removal of the plasty. In two other patients (9.5%), an increasing mobility of the plasty could be observed during skull growth. Rib plasties were not satisfying. Skull splitting or reconstruction with lyophilized bone or cartilage showed good results with a stable integration within 3-4 months. In one patient (4%), a superficial wound infection occurred, but it did not affect the plasty. From the present study, we conclude that skull splitting or the reconstruction of skull continuity by means of lyophilized bone or cartilage with fixation through biodegradable screws and bands are the methods of first choice in children, because they are fully integrated, avoid foreign material and might have a slightly lower risk of infection. In addition, removal of the implants may be avoided.(ABSTRACT TRUNCATED AT 250 WORDS)

Biodegradation, Environmental↗

Congenital intracranial cysts: clinical findings, diagnosis, treatment and follow-up. A multicenter, retrospective long-term evaluation of 72 children.

A multicenter, retrospective evaluation of 72 children born between 1973 and 1987 with intracranial cysts was performed: 37 had an arachnoid cyst, 25 a Dandy-Walker malformation and 10 a porencephalic cyst. The following criteria were evaluated: history, clinical findings, diagnostic work-up (neuroradiology, CSF and intracystic pressures), surgical therapy and follow-up (outcome and cyst volumes).

Adolescent↗

Biodegradable implant materials in fracture fixation.

Based on our experiences in paediatric traumatology treated conservatively or with metallic implants, we looked for alternative fixation possibilities in the field of biodegradables. We designed a new driving system for screws consisting of an indwelling screw driver which transduces the torque force over the whole length of the thread. With this technical approach, the head and the neck of the screw as the most friable point for the fracture of the implant could be avoided. In 48 calves aged 6 weeks we performed a comparative study with either conservative treatment (repositioning and casting) or osteosynthesis with biodegradable screws made from polylactate acid or metallic screws (AO type) after an oblique osteotomy at a 45 degrees angle to the axis of the right metacarpal bone. Results from 1 to 6 weeks postoperatively were compared and good to excellent results obtained in equal amounts for PLA and steel screw osteosynthesis, whereas conservative treatment was only successful in one third of the cases. Clinical, radiological and histological follow-up proved the feasibility of biodegradable osteosynthesis in the growing skeleton. For clinical evaluation in children, the resorption time of biodegradable materials has to be lowered to 3 to 6 months.

Animals↗

Ruptured spleen in children--15-year evolution in therapeutic concepts.

This is a 15-year retrospective study of 64 pediatric surgical patients with traumatic rupture of the spleen from 1976 to 1990. The overall mortality was 14% (9/64). All non-survivors had severe multiple traumata and no fatalities were attributable to splenic injury. During the first 5 years of the study, the traditional surgical approach of immediate laparotomy and splenectomy was employed. During the next 5 years we practised laparotomy with subtotal splenectomy and repair. During the final 5 years conservative management with clinical and ultrasonographic monitoring became predominant (1 splenectomy, 4 repair, 23 conservative treatments). Among the 55 survivors, 11 had splenectomy, 14 had splenic repairs and 30 were treated non-operatively. All survivors had excellent outcomes and there was only one complication: a local abscess following splenic repair. Based on a very strict protocol in conservative management, the total amount of transfused blood could be reduced remarkably during the last period. Splenectomized patients received pneumococcal vaccine and prophylactic antibiotic coverage was prescribed for febrile episodes. None of the splenectomized patients experienced septic episodes or increased rates of infection. Based on our experience, ultrasonographically monitored conservative management is the treatment of choice in most patients with splenic injury in childhood.

Adolescent↗

[Resorbable implants in craniofacial surgery in childhood. A contribution to the development of poly(lactide) implants].

After research on minipigs we use since 2 1/2 years our polylactid and polydixanon implants for stabilisation after osteoplastic trepanation and in craniofacial reconstructions. The presented set with headless screws and nuts and woven bands are described in detail. Biodegradable osteosynthesis was done in 15 patients aged 11 months to 17 years and two months (m: 6 years four months). The results are at least as well as with conventional steel implants (plates, screws and wires). We did not see infections in any instant, and no patient had a second operation for explantation of fixation devices. After this encouraging prospective trial we are going to simplify the construction as well as the implantation procedure and to enlarge the spectrum of indications by using plates.

Adolescent↗

[Biodegradable osteosynthesis applied to craniofacial surgery].

Since skin problems as decubitus and infections are well known risks in osteoplastic trepanations in congenital malformations in children, we searched for a reduction in size of the implants and the possibility to use biodegradable materials. After design of special constructions regarding dimension and stability purposes for children below one year, we performed osteoplastic trepanations in 27 minipigs. In 78% the healing was uneventful and the osteoplasty remained in place whereas in 22% (= 6 animals) we observed a local infection which lead to loss of implants as well as cranioplasty in 3 animals. Based on this research, we used our biodegradable implants in osteoplastic trepanations of congenital craniostenosis in children. The postoperative follow-up is now from 3 to 6 months in 4 children and the results are perfect in all. We did not observe any local infection, neither cutaneous problems, even not in bilateral frontal advancement and floating forehead procedures. The implants are presented as well as the results in animal research and the first follow-up in 4 children.

Acrocephalosyndactylia↗

[Bone healing after oblique osteotomy of the metacarpus in 6-week-old calves after conservative treatment or osteosynthesis].

Bone healing in infants treated by a rigid osteosynthesis of AO type showed mostly a marked periosteal and endosteal callus formation. In adults a callus formation is seldom seen and primary bone healing is mainly based on direct conduction of Havarian channels. Periosteal callus formation is even judged as a sign of instability in adults. We did à 2:1 osteotomy of the right metacarpal bone in 48 calves of 6 weeks of age. The treatment consisted in reposition and a plaster (6) in osteosynthesis with a metal screw of AO type (6) or a biodegradable screw of polylactid (36). The animals were sacrified 1-6 weeks postoperatively and a histological study was done in a comparative way based on the most common criteria in the literature of osteology and traumatology. In calves bones healing takes about 4-6 weeks even if the treatment is conservative or if there is a progressive dislocation in the first two postoperative weeks. A periosteal and endosteal callus formation is seen in every instance, even after interfragmentary compression by metal or biodegradable screws. All the results of biodegradable screws are at least as good as with metallic screws, at least in the growing skeleton. The force applied for interfragmentary compression does not lead to primary bone healing in the growing skeleton of young calvess.

Animals↗

[Preliminary results of biodegradable osteosynthesis in craniofacial surgery in the child].

After an experimental study on biodegradable implants for fixation purpose in skull plasties of the minipig we began a clinical trial. Six children aged 1-18 years and suffering from trigonocephaly, Morbus Apert and Morbus Crouzon as well as plagiocephaly underwent a reconstructive procedure of the skull and midface, mostly frontal advancement. The different part of skull have been fixed by biodegradable implants made of polylactate acid. Another two infants, one with a skull defect after removal of an encephalocele and the other for reconstruction of the skull after open cerebral injury and consecutive osteoclastic trepanation, have been treated with skull splitting. The two halves of the skull have been fixed by biodegradable material too. The follow-up of these 8 children now is from 2-20 months (medium 10 1/2 months). From the aesthetic point of view as well as from radiological and clinical signs we judge the result as good as with conventional materials, for example wire loops. No material had to be removed and CT scans show a fully resorption of the implants. The present paper shows the preoperative, intraoperative and postoperative evolution.

Acrocephalosyndactylia↗

[Congenital hydrocephalus--preoperative assessment and intraoperative findings in congenital hydrocephalus].

54 children already presented in Part 1 were analysed with regard to their preoperative aetiopathological findings and evolution of different parameters until surgery. Our interest was focussed on possible correlations between brain malformation and head circumference as well as both ICP and neurological evolution. We examined the presence of infectious diseases in the preoperative period and checked on the advantage of a perioperative antibiotic therapy. We could not find any correlation between the aetiopathological findings in X-ray investigation and head circumference or ICP or preoperative neurological findings. Perioperative antibiotic therapy does not seem to be an additional safety factor.

Anti-Bacterial Agents↗

[Knee injury in childhood: a retrospective analysis of patients of the Zurich Pediatric Surgery University Clinic].

During the past 10 years (1976-1985) we treated more than 1000 knee injuries at our department. More than 90% were minor traumas and could be treated on an outpatient basis. In 78 children x-ray or clinical examination revealed a haemarthros which was confirmed by aspiration. This group represents 7.6% of patients. In 38 patients a major knee injury led to surgical treatment. Conservative treatment was successful in 40 children. In 26 cases we could not find the origin of haemarthrosis by clinical or radiological examination. 14 children showed major lesions, mostly undislocated fractures of the patella or avulsion of the cruciate ligaments. In all 78 patients haemarthrosis was evacuated by aspiration or during operation and the injured knee joint was immobilised for 4-6 weeks. 56 of the 78 patients (72%) were radiologically and clinically re-evaluated after 5 1/2 years (1-11 years). The aim of this presentation is to judge, based on our own patients, if arthroscopy in paediatric knee injuries is mandatory in every case as demanded by different authors. We were most interested to find out whether diagnostic errors lead to false, positive or negative indication for operation. In very few cases only our diagnosis was based on arthroscopic evaluation.

Adolescent↗