Novel surgical and imaging methods of the middle ear and temporal bone

Välikorvaleikkauksiin usein liittyvän välikorvan ja kuuloluuketjun kirurgisen rekonstruktion tavoitteena on luoda olosuhteet, jotka mahdollistavat hyvän kuulon sekä välikorvan säilymisen tulehduksettomana ja ilmapitoisena. Välikorvan rekonstruktiossa on käytetty implanttimateriaaleina perinteisesti potilaan omia kudoksia sekä tarvittaessa erilaisia hajoamattomia biomateriaaleja, mm. titaania ja silikonia. Ongelmana biomateriaalien käytössä voi olla bakteerien adherenssi eli tarttuminen vieraan materiaalin pintaan, mikä saattaa johtaa biofilmin muodostumiseen. Tämä voi aiheuttaa kroonisen, huonosti antibiootteihin reagoivan infektion kudoksessa, mikä usein käytännössä johtaa uusintaleikkaukseen ja implantin poistoon. Maitohappo- ja glykolihappopohjaiset biologisesti hajoavat polymeerit ovat olleet kliinisessä käytössä jo vuosikymmeniä. Niitä on käytetty erityisesti tukimateriaaleina mm. ortopediassa sekä kasvo- ja leukakirurgiassa. Niitä ei ole toistaiseksi käytetty välikorvakirurgiassa. Korvan kuvantamiseen käytetään ensisijaisesti tietokonetomografiaa (TT). TT-tutkimuksen ongelmana on potilaan altistuminen suhteellisen korkealle sädeannokselle, joka kasvaa kumulatiivisesti, jos kuvaus joudutaan toistamaan. Väitöskirjatyö selvittää uuden, aiemmin kliinisessä työssä rutiinisti lähinnä hampaiston ja kasvojen alueen kuvantamiseen käytetyn rajoitetun kartiokeila-TT:n soveltuvuutta korvan alueen kuvantamiseen. Väitöskirjan kahdessa ensimmäisessä osatyössä tutkittiin ja verrattiin kahden kroonisia ja postoperatiivisia korvainfektioita aiheuttavan bakteerin, Staphylococcus aureuksen ja Pseudomonas aeruginosan, in vitro adherenssia titaanin, silikonin ja kahden eri biohajoavan polymeerin (PLGA) pintaan. Lisäksi tutkittiin materiaalien albumiinipinnoituksen vaikutusta adherenssiin. Kolmannessa osatyössä tutkittiin eläinmallissa PLGA:n biokompatibiliteettia eli kudosyhteensopivuutta kokeellisessa välikorvakirurgiassa. Chinchillojen välikorviin istutettiin PLGA-materiaalia, eläimiä seurattiin, ja ne lopetettiin 6 kk:n kuluttua operaatiosta. Biokompatibiliteetin arviointi perustui kliinisiin havaintoihin sekä kudosnäytteisiin. Neljännessä osatyössä tutkittiin kartiokeila-TT:n soveltuvuutta korvan alueen kuvantamiseen vertaamalla sen tarkkuutta perinteisen spiraali-TT:n tarkkuuteen. Molemmilla laitteilla kuvattiin ohimo- eli temporaaliluita korvan alueen kliinisesti ja kirurgisesti tärkeiden rakenteiden kuvantumisen tarkkuuden arvioimiseksi. Viidennessä osatyössä arvioitiin myös operoitujen temporaaliluiden kuvantumista kartiokeila-TT:ssa. Bakteeritutkimuksissa PLGA-materiaalin pintaan tarttui keskimäärin korkeintaan saman verran tai vähemmän bakteereita kuin silikonin tai titaanin. Albumiinipinnoitus vähensi bakteeriadherenssia merkitsevästi kaikilla materiaaleilla. Eläinkokeiden perusteella PLGA todettiin hyvin siedetyksi välikorvassa. Korvakäytävissä tai välikorvissa ei todettu infektioita, tärykalvon perforaatioita tai materiaalin esiin työntymistä. Kudosnäytteissä näkyi lievää tulehdusreaktiota ja fibroosia implantin ympärillä. Temporaaliluutöissä rajoitettu kartiokeila-TT todettiin vähintään yhtä tarkaksi menetelmäksi kuin spiraali-TT välikorvan ja sisäkorvan rakenteiden kuvantamisessa, ja sen aiheuttama kertasäderasitus todettiin spiraali-TT:n vastaavaa huomattavasti vähäisemmäksi. Kartiokeila-TT soveltui hyvin välikorvaimplanttien ja postoperatiivisen korvan kuvantamiseen. Tulokset osoittavat, että PLGA on välikorvakirurgiaan soveltuva, turvallinen ja kudosyhteensopiva biomateriaali. Biomateriaalien pinnoittaminen albumiinilla vähentää merkittävästi bakteeriadherenssia niihin, mikä puoltaa pinnoituksen soveltamista implanttikirurgiassa. Kartiokeila-TT soveltuu korvan alueen kuvantamiseen. Sen tarkkuus kliinisesti tärkeiden rakenteiden osoittamisessa on vähintään yhtä hyvä ja sen potilaalle aiheuttama sädeannos pienempi kuin nykyisen korva-spiraali-TT:n. Tämä tekee menetelmästä spiraali-TT:aa potilasturvallisemman vaihtoehdon erityisesti, jos potilaan tilanne vaatii seurantaa ja useampia kuvauksia, ja jos halutaan kuvata rajoitettuja alueita uni- tai bilateraalisesti.

Hormone therapy in elderly women; a comparative study with alendronate of the effects on bone, cardiovascular risk factors, periodontal conditions and quality of life

Thirty percent of 70-year-old women have osteoporosis; after age of 80 its prevalence is up to 70%. Postmenopausal women with osteoporosis seem to be at an increased risk for cardiovascular events, and deterioration of oral health, as shown by attachment loss of teeth, which is proportional to the severity of osteoporosis. Osteoporosis can be treated with many different medication, e.g. estrogen and alendronate. We randomized 90 elderly osteoporotic women (65-80 years of age) to receive hormone therapy (HT)(2mg E2+NETA), 10mg alendronate, and their combination for two years and compared their effects on bone mineral density (BMD) and turnover, two surrogate markers of the risk of cardiovascular diseases, C-reactive protein (CRP) and E-selectin, as well as oral health. The effect of HT on health-related quality of life (HRQoL) was studied in the population-based cohort of 1663 postmenopausal women (mean age 68 yr) (585 estrogen users and 1078 non-users). BMD was measured with dual-energy X-ray absorptiometry (DXA) at 0, 12 and 24 months. Urinary N-telopeptide (NTX) of type I collagen, a marker of bone resorption, and serum aminoterminal propeptide of human type I procollagen (PINP), a marker of bone formation, were measured every six months of treatment. Serum CRP and E-selectin, were measured at 0, 6, and 12 months. Dental, and periodontal conditions, and gingival crevicular fluid (GCF) matrix metalloproteinase (MMP)-8 levels were studied to evaluate the oral health status and for the mouth symptoms a structured questionnaire was used. The HRQoL was measured with 15D questionnaire. Lumbar spine BMD increased similarly in all treatment groups (6.8-8.4% and 9.1-11.2%). Only HT increased femoral neck BMD at both 12 (4.9%) and 24 months (5.8%), at the latter time point the HT group differed significantly from the other groups. HT reduced bone marker levels of NTX and PINP significantly less than other two groups.Oral HT significantly increased serum CRP level by 76.5% at 6 and by 47.1% (NS) at 12 months, and decreased serum E-selectin level by 24.3% and 30.0%. Alendronate had no effect on these surrogate markers. Alendronate caused a decrease in the resting salivary flow rate and tended to increase GCF MMP-8 levels. Otherwise, there was no effect on the parameters of oral health. HT improved the HRQoL of elderly women significantly on the dimensions of usual activities, vitality and sexual activity, but the overall improvement in HRQoL was neither statistically significant nor clinically important. In conclusion, bisphosphonates might be the first option to start the treatment of postmenopausal osteoporosis in the old age.

Impact of hysterectomy or levonorgestrel-releasing intrauterine system on ovarian function, bone, and sexual functioning in menorrhagic patients

The `VuoKKo` trial consisted of 236 women referred and randomised due to menorrhagia in the five university hospitals of Finland between November 1994 and November 1997. Of these women, 117 were randomised to hysterectomy and 119 to use levonorgestrel-releasing intrauterine system (LNG-IUS) to treat this complaint. Their follow-up visits took place six and twelve months after the treatment and five years after the randomisation. The first aim in the primary trial was quality-of-life and monetary aspects, and secondly in the present study to compare ovarian function, bone mineral density (BMD) and sexual functioning after these two treatment options. Ovarian function seemed to decrease after hysterectomy, demonstrated by increased hot flashes and serum follicle-stimulating hormone concentrations twelve months after the operation. Such an increase was not seen among LNG-IUS users. The pulsatility index of intraovarian arteries measured by two-dimensional ultrasound decreased in the hysterectomy group, but not in the LNG-IUS group. The decrease in serum inhibin B concentrations was similar in both groups, while ovarian artery circulation remained unchanged. BMD of the women measured by dual x-ray absorptiometry (DXA) at the lumbar spine and femoral neck at baseline and at five years after treatment showed BMD decrease at the lumbar spine among hysterectomised women, but not among LNG-IUS users. In both groups, BMD at the femoral neck had decreased. Differences between the groups were not, however, significant. Sexual functioning assessed by McCoy s sexual scale showed that sexual satisfaction as well as intercourse frequency had increased and sexual problems decreased among hysterectomised women six months after treatment. Among LNG-IUS users, sexual satisfaction and sexual problems remained unchanged. Although, the two groups did not differ in terms of sexual satisfaction or sexual problems at one-year and five-year follow-ups, LNG-IUS users were less satisfied with their partners than hysterectomised women.

The effects of low-intensity ultrasound in bioabsorbable self-reinforced poly-L-lactide -fixed cancellous bone fracture

The purpose of the present study was to investigate the effects of low-intensity ultrasound on bioabsorbable self-reinforced poly-L-lactide (SR-PLLA) screws and on fracture healing after SR-PLLA device fixation in experimental and clinical cancellous bone fracture. In the first experimental study, the assessment of the mechanical strengths of the SR-PLLA screws was performed after 12 weeks of daily 20-minute ultrasound exposure in vitro. In the second experimental study, 32 male Wistar rats with an experimental distal femur osteotomy fixed with an SR-PLLA rod were exposed for daily low-intensity ultrasound treatment for 21 days. The effects on the healing bone were assessed. The clinical studies consist of three prospective, randomized, and placebo-controlled series of dislocated lateral malleolar fractures fixed with one SR-PLLA screw. The total number of the patients in these series was 52. Half of the patients were provided randomly with a sham ultrasound device. The patients underwent ultrasound therapy 20 minutes daily for six weeks. Radiological bone healing was assessed both by radiographs at two, six, nine, and 12 weeks and by multidetector computed tomography (MDCT) scans at two weeks, nine weeks, and 18 months. Bone mineral density was assessed by dual-energy X-ray absorptiometry (DXA). The clinical outcome was assessed by both Olerud-Molander scoring and clinical examination of the ankle. Low-intensity ultrasound had no effects on the mechanical properties and degradation behaviour of the SR-PLLA screws in vitro. There were no obvious signs of low-intensity ultrasound-induced enhancement in the bone healing in SR-PLLA-rod-fixed metaphyseal distal femur osteotomy in rats. The biocompatibility of low-intensity ultrasound treatment and SR-PLLA was found to be good. In the clinical series low-intensity ultrasound was observed to have no obvious effects on the bone mineral density of the fractured lateral malleolus. There were no obvious differences in the radiological bone healing times of the SR-PLLA-screw-fixed lateral malleolar fractures after low-intensity ultrasound treatment. Low-intensity ultrasound did not have any effects on radiological bone morphology, bone mineral density or clinical outcome 18 months after the injury. There were no obvious findings in the present study to support the hypothesis that low-intensity pulsed ultrasound enhances bone healing in SR-PLLA-rod-fixed experimental metaphyseal distal femur osteotomy in rats or in clinical SR-PLLA-screw-fixed lateral malleolar fractures. It is important to limit the conclusions of the present set of studies only to lateral malleolar fractures fixed with an SR-PLLA screw.

Evaluation of the Biocompatibility of Poly (ortho ester), Copolymer of ε-caprolactone/D,L-lactide and the Composite of Copolymer of ε-caprolactone/D,L-lactide and Tricalciumphosphate as Bone Filling Material

The purpose of this series of studies was to evaluate the biocompatibility of poly (ortho) ester (POE), copolymer of ε-caprolactone and D,L-lactide [P (ε-CL/DL-LA)] and the composite of P(ε-CL/DL-LA) and tricalciumphosphate (TCP) as bone filling material in bone defects. Tissue reactions and resorption times of two solid POE-implants (POE 140 and POE 46) with different methods of sterilization (gamma- and ethylene oxide sterilization), P(ε-CL/DL-LA)(40/60 w/w) in paste form and 50/50 w/w composite of 40/60 w/w P(ε-CL/DL-LA) and TCP and 27/73 w/w composite of 60/40 w/w P(ε-CL/DL-LA) and TCP were examined in experimental animals. The follow-up times were from one week to 52 weeks. The bone samples were evaluated histologically and the soft tissue samples histologically, immunohistochemically and electronmicroscopically. The results showed that the resorption time of gamma sterilized POE 140 was eight weeks and ethylene oxide sterilized POE 140 13 weeks in bone. The resorption time of POE 46 was more than 24 weeks. The gamma sterilized rods started to erode from the surface faster than ethylene oxide sterilized rods for both POEs. Inflammation in bone was from slight to moderate with POE 140 and moderate with POE 46. No highly fluorescent layer of tenascin or fibronectin was found in the soft tissue. Bone healing at the sites of implantation was slower than at control sites with the copolymer in small bone defects. The resorption time for the copolymer was over one year. Inflammation in bone was mostly moderate. Bone healing at the sites of implantation was also slower than at the control sites with the composite in small and large mandibular bone defects. Bone formation had ceased at both sites by the end of follow-up in large mandibular bone defects. The ultrastructure of the connective tissue was normal during the period of observation. It can be concluded that the method of sterilization influenced the resorption time of both POEs. Gamma sterilized POE 140 could have been suitable material for filling small bone defects, whereas the degradation times of solid EO-sterilized POE 140 and POE 46 were too slow to be considered as bone filling material. Solid material is difficult to contour, which can be considered as a disadvantage. The composites were excellent to handle, but the degradation time of the polymer and the composites were too slow. Therefore, the copolymer and the composite can not be recommended as bone filling material.

Bone Stress Injuries of the Foot and Ankle

Bone stress injuries of the foot have been known for more than 150 years. For a century, their primary diagnostic imaging tool has been radiography. However, currently the golden standard for establishing the diagnosis of stress injuries is magnetic resonance imaging (MRI). Although the injury type has been fairly well documented in the earlier literature, little information is available on the healing of stress injuries located in e.g. the talus and calcaneus. The current study retrospectively evaluated the stress injuries of the foot and ankle treated at the Central Military Hospital over a period of eight years in patients who underwent MRI for stress injury of the foot. The imaging studies of the patients were reevaluated to determine the exact nature of the stress injury. Moreover, the hospital records of the patients were reviewed to determine the healing of stress injuries of the talus and calcaneus. Patients with a stress fracture in the talus were recalled for a follow-up examination and MRI scan one to six years after the initial injury to determine if the fracture had completely healed, clinically and radiologically. The bone stress injuries of the foot were found to affect more than one bone in a majority of the cases. The talus and the calcaneus were the bones most commonly affected. In the talus, the most common site for the injuries was the head of the bone, and in the calcaneus, the posterior part of the bone. The injuries in these bones were associated with injuries in the surrounding bones. Stress injuries in the calcaneus seemed to heal well. No complications were seen in the primary healing process. The patients were, however, sometimes compelled to refrain from physical training for up to months. In the talus, minor degenerative findings of the articular surface were seen in half of the patients who participated in a follow-up MRI scan and radiographs taken one to six years after the initial injury. Half of the patients also reported minor exercise related symptoms in the follow-up. The symptoms were, however, not noticeable in everyday life.

Bone health and vitamin D status in children with motor disability and adults with intellectual disability

Osteoporosis is not only a disease of the elderly, but is increasingly diagnosed in chronically ill children. Children with severe motor disabilities, such as cerebral palsy (CP), have many risk factors for osteoporosis. Adults with intellectual disability (ID) are also prone to low bone mineral density (BMD) and increased fractures. This study was carried out to identify risk factors for low BMD and osteoporosis in children with severe motor disability and in adults with ID. In this study 59 children with severe motor disability, ranging in age from 5 to 16 years were evaluated. Lumbar spine BMD was measured with dual-energy x-ray absorptiometry. BMD values were corrected for bone size by calculating bone mineral apparent density (BMAD), and for bone age. The values were transformed into Z-scores by comparison with normative data. Spinal radiographs were assessed for vertebral morphology. Blood samples were obtained for biochemical parameters. Parents were requested to keep a food diary for three days. The median daily energy and nutrient intakes were calculated. Fractures were common; 17% of the children had sustained peripheral fractures and 25% had compression fractures. BMD was low in children; the median spinal BMAD Z-score was -1.0 (range -5.0 – +2.0) and the BMAD Z-score <-2.0 in 20% of the children. Low BMAD Z-score and hypercalciuria were significant risk factors for fractures. In children with motor disability, calcium intakes were sufficient, while total energy and vitamin D intakes were not. In the vitamin D intervention studies, 44 children and adolescents with severe motor disability and 138 adults with ID were studied. After baseline blood samples, the children were divided into two groups; those in the treatment group received 1000 IU peroral vitamin D3 five days a week for 10 weeks, and subjects in the control group continued with their normal diet. Adults with ID were allocated to receive either 800 IU peroral vitamin D3 daily for six months or a single intramuscular injection of 150 000 IU D3. Blood samples were obtained at baseline and after treatment. Serum concentrations of 25-OH-vitamin D (S-25-OHD) were low in all subgroups before vitamin D intervention: in almost 60% of children and in 77% of adults the S-25-OHD concentration was below 50 nmol/L, indicating vitamin D insufficiency. After vitamin D intervention, 19% of children and 42% adults who received vitamin D perorally and 12% of adults who received vitamin D intramuscularly had optimal S-25-OHD (>80 nmol/L). This study demonstrated that low BMD and peripheral and spinal fractures are common in children with severe motor disabilities. Vitamin D status was suboptimal in the majority of children with motor disability and adults with ID. Vitamin D insufficiency can be corrected with vitamin D supplements; the peroral dose should be at least 800 IU per day.