[Bisphosphonates inhibit matrix metalloproteinases--a new possible mechanism of action].
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Diphosphonates↗
Biomedical subjects
C Lindqvist
Publications and source records attributed to C Lindqvist.
The role of alpha2 beta1 and alpha3 beta1 integrin receptors in the initial anchoring of MDA-MB-231 human breast cancer cells to cortical bone matrix.
Molecular mechanisms involved in the rapid attachment of the human breast cancer cell line MDA-MD-231 to cortical bone matrix were studied. The attachment of MDA-MD-231 cells to cortical bone disks could be blocked by 75% when cells were pretreated with a monoclonal antibody to the beta1-subunit of the integrin family. Monoclonal antibodies against the alpha2, alpha3, and alpha5 integrin subunits inhibited the attachment by 76, 26, and 8 % respectively. Collagenase type I and collagen type I antibody blocked the cell attachment by 45 and 50 % whereas pretreatment of the cells with soluble collagen type I blocked the attachment by 85 %. Our study with a panel of cancer cell lines further showed a close correlation between alpha2 beta1 and alpha3 beta1 integrin receptor expression and the capability to attach to cortical bone. These receptors appear to be the key receptors utilized by cancer cells for the initial attachment to cortical bone, and this could facilitate the localization of alpha2 beta1 and alpha3 beta1 expressing cancer cells to the skeleton.
Animals↗
Homogeneous time-resolved IL-2-IL-2R alpha assay using fluorescence resonance energy transfer.
A homogeneous receptor-ligand assay based on fluorescence resonance energy transfer is described. In the assay, recombinant human interleukin 2 (IL-2) and a monoclonal antibody against the human IL-2 receptor alpha chain were labelled with a highly fluorescent europium chelate and Cy5, respectively. As a result of a successful receptor-ligand complex formation, these labels are brought into close proximity, which will thereby allow an energy transfer to occur from the donor (europium) to the acceptor (Cy5), upon excitation of the donor. Utilization of specific non-neutralizing antibodies made it possible to use crude hIL-2R alpha membranes prepared from recombinant baculovirus-infected Sf9 insect cells. The specific energy transfer was measured at the emission wavelength of Cy5 using a time-resolved fluorometer. The data presented, demonstrate that this assay design can be utilized for saturation as well as competitive binding experiments in addition to regular receptor titrations. As a rapid simple homogeneous assay it is particularily suitable for high throughput screening analyses.
Animals↗
A 5-year in vitro and in vivo study of the biodegradation of polylactide plates.
PURPOSE: The purpose of this study was to investigate the long-term tissue response and duration of degradation of self-reinforced poly-L-lactide (SR-PLLA) multilayer plates in vivo. MATERIALS AND METHODS: Mandibular osteotomies in sheep were fixed with SR-PLLA multilayer plates. The animals were followed for 1, 2, 3, 4, and 5 years, after which histologic studies were performed. RESULTS: The foreign-body reaction was mainly mild, and the osteotomies were well united. After 5 years in vivo, the material was almost completely resorbed, but small particles of polymer could still be detected at the implantation site. SR-PLLA plates were also incubated in vitro for 5 years. The material degraded considerably faster in vivo than in vitro. Molecular weight, melting temperature, and crystallinity of the plates remained at a constant level after 2 years in vitro, indicating very slow degradation of the oligomeric (molecular weight [Mw], 3500 daltons), highly crystalline (heat of fusion, 70 J/g), PLLA residue solely as a result of hydrolysis. Although the plates became increasingly fragile as they degraded, they retained their macroscopic form until the end of the 5-year follow-up. Loss of mass of the plates was 52%+/-8% after 5 years of incubation in vitro. CONCLUSIONS: Although the long degradation period may seem to be a minor drawback to the use of such plates, it does not appear to affect the healing process.
Absorption↗
Occlusal and temporomandibular joint disorders in patients with unilateral condylar fracture. A prospective one-year study.
Adult dentate patients with unilateral condylar fractures were followed up for one year after injury. Patients were interviewed about subjective complaints, and mandibular excursions and function of occlusion and temporomandibular joints (TMJs) were recorded. Radiological characteristics were assessed from panoramic and Towne's views and compared between patients with occlusal disorders and patients without. During follow up, mandibular deviation on opening towards the fractured side was more pronounced in cases with marked reduction of ramus height and condylar dislocation. This restriction of translation movement of the fractured joint was also seen radiologically in one-third of cases while in two-thirds of the fractured condyles, malpositioning was observed when compared with the healthy side. In patients (39%) having subjective symptoms such as TMJ pain, altered occlusion or ability to bite only unilaterally, and objectively verified occlusal interferences, a marked reduction of the ramus height on the fractured side was observed. In such cases nonoperative treatment of condylar fractures may be compromised.
Adolescent↗
Skeletal stability following mandibular advancement and rigid fixation with polylactide biodegradable screws.
Skeletal stability during the first year after mandibular advancement surgery and fixation using biodegradable self-reinforced poly-l-lactide (SR-PLLA) screws, without postoperative intermaxillary fixation, was studied in 25 patients by means of cephalometric measurements. The magnitude of advancement was on average, 3.88 mm at pogonion (PG) (range 1.25-6.5 mm) and 4.57 mm at B-point (range 2.75-7.5 mm). After one year a mean relapse backwards of 0.59 mm at the PG (15%) and 0.78 mm at the B-point (17%) was observed. Nineteen patients (76%) and 17 patients (68%) were stable at PG and B-point, respectively. SR-PLLA screws are considered to be comparable to other forms of rigid internal fixation for fixation of bilateral splitting osteotomies after mandibular advancement, as far as skeletal stability is concerned.
Absorption↗
Biodegradable polylactide plates and screws in orthognathic surgery: technical note.
In orthognathic surgery, the bone fragments are usually fixed with metallic plates and screws. Metallic devices other than titanium plates are usually removed after the osteotomy has consolidated, which often requires general anaesthesia. Titanium plates, supposed to be biotolerable, have been introduced in order to overcome this need for secondary intervention. However, due to corrosion, titanium particles have been found in scar tissue covering these plates and in locoregional lymph nodes. Therefore, their removal is also advocated. Self-reinforced poly (L-lactide) homopolymer (PLLA) and poly (L/D-lactide) stereocopolymers with a L/D molar ratio up to 85/15 have sufficient strength to overcome the need for additional support for the fixation of fractures. The plates can be bent at room temperature. The surgical technique and early results of a case of bimaxillary surgery and genioplasty fixed with bioresorbable material without postoperative rigid maxillomandibular fixation are reported.
Absorption↗
Radiologic changes of the temporomandibular joint after condylar fractures in childhood.
OBJECTIVE: The purpose of this investigation was to study the radiologic outcomes of pediatric condylar fractures. STUDY DESIGN: Radiographs of 37 patients with 45 condylar fractures that had been diagnosed at the Department of Oral and Maxillofacial Surgery, Helsinki University Central Hospital were retrospectively reviewed. The frequency and characteristics of incomplete remodeling at an average of 4.1 years after the injury were studied. The influence of age and fracture type on remodeling were considered. RESULTS: Incomplete remodeling was observed after 56% of the fractures. The most frequent signs of incomplete remodeling were alteration in the configuration of the surface of the condylar head and deformation of the condylar neck. Incomplete remodeling was frequently (83%) related to fracture dislocation. For this fracture type the radiologic prognosis seems poor in all age groups. A difference in ramus height between the 2 sides was observed in 52% of the fractures, particularly frequently (80%) after fracture dislocation. CONCLUSIONS: Radiologic aberrations are frequent after pediatric condylar fractures. Dislocated fractures, in particular, need special attention and long-lasting clinical follow-up.
Adolescent↗
Fibrous wound repair associated with biodegradable poly-L/D-lactide copolymer implants: study of the expression of tenascin and cellular fibronectin.
Extracellular matrix (ECM) proteins are known to play a role in inflammatory and hyperplastic processes. Our aim in the present study was to study the distribution of tenascin (Tn), cellular fibronectins (cFn) and myofibroblasts around biodegradable poly-L/D-lactide (PLA) implants with monoclonal antibodies (MAb). Ethylene-oxide and gamma-irradiation sterilized PLA plate-type implants were inserted into the dorsal subcutaneous tissue of ten adult rabbits. Follow-up times were 4, 12, 16, 36 and 48 wk. Only some inflammatory cells were observed. In electron microscopy, a close coherence between the implant and the stromal tissue was seen. Immunoreactivity for Tn, cFn and alpha-actin was detected as a distinct layer bordering the implant, regardless of the sterilization method for the first 36 wk. From week 36 onwards, Tn immunoreactivity was downregulated while cFn immunoreactivity still persisted. A moderate upregulation for myofibroblasts was seen on the week 48 specimens, when hydrolysation of PLA implant had started. The persistent content of myofibroblasts, Tn and cFn suggests a prolonged wound healing produced by PLA implants. The absence of Tn at the week 48 specimens suggests that cFn, rather than Tn may be needed for alpha-actin-mediated contraction by myofibroblasts.
Journal Article↗
Malpractice claims for permanent nerve injuries related to third molar removals.
On the basis of the register of the Finnish Patient Insurance Association, the aim of this study was to examine malpractice claims for nerve injuries associated with third molar removals and determine whether they are concentrated among specialists, among less experienced dentists, or in certain geographic areas. During 1987-93 there were 139 claims for permanent sensory or motor disturbances related to removal of lower third molars in Finland. The lingual nerve was injured in 54% and the inferior alveolar nerve in 41% of the claims. In 91% of the cases the injury occurred in relation to surgical removal of the tooth and in 6% in relation to simple extraction. The claims were distributed among 123 dentists, of whom 78% were dental surgeons, 15% specialists in oral and maxillofacial surgery, and 7% other specialists. These figures represented 2% of the dental surgeons and 26% of the oral surgeons in Finland (P< 0.01). More than half the claims were associated with dentists with less than 10 years' experience. Claims originated more often from the eastern and northern (rural) areas of Finland than from urban areas (3.8 claims versus 2.4 claims per 100,000 inhabitants, P < 0.05). Compensation was paid to the patients in two-thirds of the cases, indicating that the dentists authorized to decide claims very often considered these injuries avoidable. Therefore, proper diagnosis, treatment planning, surgical techniques, and detailed patient information must be emphasized. In cases where risks are obvious, referral to an oral surgeon is recommended.
Adolescent↗
[Clinical nursing--nursing home develops a pressure sore record. Interview by Kjell Arne Bakke].
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Aged↗
Inhibition of matrix metalloproteinase-1 by dichloromethylene bisphosphonate (clodronate).
Interstitial collagenase present in human jaw cyst extract and purified human fibroblast-type collagenase (MMP-1) were both efficiently inhibited in vitro by clodronate, an osteoactive, antiresorptive bisphosphonate. The IC50 of clodronate to inhibit MMP-1 is 150 microM. These findings suggest an extended and hitherto undescribed properties for clodronate/biphosphonates in prevention and treatment of tissue degradation in both bone and soft tissue destructive diseases.
Bone Diseases↗
Solid phase IL-2-IL-2R alpha assay with time resolved fluorometry.
A time-resolved fluorometric, solid phase, receptor ligand interaction assay is described. The assay consists of wells coated with anti-human IL-2 receptor alpha (hIL-2R alpha) monoclonal antibodies (mAb), europium labelled hIL2 (Eu-IL-2) and human recombinant IL-2 receptor alpha subunits expressed in the baculovirus expression vector system (BEVS). In the assay hIL-2R alpha-Eu-IL-2 complexes bind to the solid phase mAb. Receptor bound Eu is dissociated into an enhancer solution where it forms highly fluorescent complexes. The fluorescence is measured in a time-resolved fluorometer. The Kd value calculated from the saturation curve is in good agreement with previously reported values for the low affinity type of IL-2R, making the described assay a simple and nonradioactive alternative for measurement of soluble hIL-2R alpha in biological systems. Furthermore this assay format provides convenient separation of bound ligand from unbound and is therefore suitable for high throughput screenings.
Europium↗
An epidemiological study of patterns of condylar fractures in children.
OBJECTIVE: To find out how the site and type of condylar fracture are affected by its aetiology and the age and sex of the patient. DESIGN: Retrospective study. SETTING: Tertiary referral centre, Finland. MATERIAL: Radiographs of 101 children (aged 15 years or less) with 119 condylar fractures. MAIN OUTCOME MEASURES: Site of fracture and degree of displacement. RESULTS: A total of 26 of the 119 fractures were intracapsular (22%) and 93 (78%) extracapsular. Only among patients less than 6 years of age was there a preponderance of intracapsular fractures (7/12 fractures in 10 patients, 58%). In the older children 78% (83/107) were in the condylar neck. There were few subcondylar fractures (5/119, 4%). Only 6 fractures were displaced (5%). Dislocation of the condyle from the glenoid fossa was common in all age groups. CONCLUSION: The site of condylar fracture is age related, but not associated with sex or aetiology.
Accidents, Traffic↗
Mandibular osteotomy fixed with biodegradable plates and screws: an animal study.
The objective of the study was to evaluate the use of a totally biodegradable fixation device in the fixation of mandibular osteotomy in sheep. Mandibular unilateral body osteotomies were fixed with biodegradable self-reinforced poly-L-lactide (SR-PLLA) multi-layer plates and screws in nine sheep. The unoperated sides acted as control. The follow-up times were 6, 12 and 24 weeks, after which radiological, mechanical and histological studies were carried out. An analysis of the implanted material was also carried out. The results showed that the SR-PLLA plates and screws were strong enough to fix the osteotomy and that the osteotomies healed mainly with callus formation. Therefore we conclude that SR-PLLA multi-layer plates and screws can be used together successfully in the fixation of mandibular osteotomies without maxillomandibular fixation. However, before they can be used in humans, the size of the plate and screws should be decreased.
Animals↗
Oral sources of septicaemia in patients with malignancies.
This article reviews papers dealing with oral infections of adult septicaemia patients, searched from MEDLINE, Current Contents and Core Biomedical Collection databases from January 1966 to November 1996. Case reports were excluded. The systematic review of literature revealed that our knowledge of the topic is mostly based on very small patient material. There are no multicentre studies on the effects of various oral health treatment modes on the prevention of septicaemia of oral origin. The number of controlled and comparative studies on the efficacy of the different treatment protocols of oral infections is also small. Current recommendations in this respect are mainly empirical and not evidence based. Clinical practice guidelines are therefore urgently needed. Nevertheless, close co-operation between oncological and oral health units is emphasised because many studies have shown that the oral cavity is indeed an important source of bacteraemia. Life-threatening infections may follow if maintenance of oral health is neglected during anticancer therapy and if potential oral infection foci are left untreated before immunosuppressive therapy.
Adult↗
Five-year follow-up study of saliva, mutans streptococci, lactobacilli and yeast counts in lymphoma patients.
Twenty-two patients out of the 79 that were originally included were examined 5 years after beginning anticancer therapy for lymphomas. The patients' cumulative data on salivary flow rate, buffering capacity and acidogenic microbial counts were compared with respective data of 17 patients who died during the follow-up. Stimulated saliva samples had been taken at baseline and during the cytostatic treatment with combination chemotherapy, and 1 year and 5 years later. Chair-side kits were used at the hospital ward for the assessment of the study parameters. Mean saliva flow at baseline was 1.5 +/- 0.7 ml/min in the surviving group and 1.5 +/- 0.8 ml/min in the deceased. Salivary flow rates were not affected by the anticancer treatment and there was no statistically significant difference between the groups in this respect. A significant difference was observed between the groups in salivary buffering capacity values at baseline: only 32% of the survived had low buffering capacity in comparison to 69% of those who later died (P < 0.02). Buffering capacity values remained low in 50% of the surviving patients 5 years later. Higher mutans streptococci and lactobacilli counts were seen among the deceased than in the survived patients but mutans streptococci decreased significantly in both groups after the start of the anticancer therapy (P < 0.05). The number of positive yeast counts increased consistently during the chemotherapy in both groups, being higher in the survived when compared with the deceased patients. Yeast counts remained positive 5 years later in 73% of the survived patients, while the mean mutans streptococci and lactobacilli counts decreased below baseline values. The results showed that persistently high salivary microbial counts and low buffering capacity may be linked with poor prognosis.
Adult↗
Five-year follow-up of saliva in patients treated for lymphomas.
OBJECTIVE: Patients treated for Hodgkin's disease and non-Hodgkin lymphomas were followed for 5 years after start of therapy. The patients received combinations of anticancer drugs for curative intent for 6 months (Hodgkin's disease) or 7 months (non-Hodgkin lymphomas). STUDY DESIGN: Cumulated data of 22 surviving patients (mean age, 49 years) were compared with that of 17 patients (mean age, 52 years) who had died or were terminally ill at the 5-year examination. Saliva samples were taken at baseline, and 4, 6, 12, and 60 months after start of chemotherapy. Salivary flow rate and a variety of biochemical constituents were analyzed. RESULTS: The results showed no long-term effect of anticancer treatment on salivary flow rates. Neither was there any difference between the surviving or deceased patients' baseline values (1.5 +/- 0.7 mL/minute versus 1.5 +/- 0.8 mL/minute) and after chemotherapy. Lysozyme, IgA, IgG, and IgM concentrations decreased after chemotherapy. Significantly lower values were observed at the 5-year examination than at baseline. This was particularly evident in IgA, which is the major immunoglobulin in saliva; mean IgA was 70.5 +/- 52.8 mg/mL at baseline, 35.8 +/- 15.0 mg/mL 5 years later (p < 0.001). Salivary total protein and amylase concentrations were significantly decreased (p < 0.001 and p < 0.05, respectively), whereas albumin concentration was significantly increased at the 5-year examination (p < 0.05). When the salivary biochemical results were compared between the surviving and deceased patients, no statistically significant differences were observed. At baseline, however, the mean immunoglobulin values were lower in patients who later died, in comparison with those who survived. CONCLUSIONS: These results showed that modern anticancer therapy need not cause severe side effects on salivary flow rates and composition. In addition, apart from the long-term immunosuppression, no significant decreases were expressed in salivary defensive factors.
Adult↗