Tumour-associated urokinase-type plasminogen activator (uPA) and its inhibitor PAI-1 in normal and neoplastic tissues of patients with squamous cell cancer of the oral cavity - clinical relevance and prognostic value.

The central role of the serine protease urokinase-type plasminogen activator (uPA) and its inhibitor, the plasminogen activator-inhibitor-1 (PAI-1), in tumour invasion and metastasis becomes more and more evident. In several studies, uPA and PAI-1 proved to be of prognostic relevance as shown for different types of cancer (e.g. breast, stomach, lung). Elevated antigen levels of uPA and/or PAI-1 predict poor outcome (relapse-free survival) for patients afflicted with cancer. For oral squamous cell carcinomas, however, the prognostic relevance of the tumour-associated proteolytic factors uPA and PAI-1 has still to be evaluated. In the present study, using tissue extracts of 79 oral cancer cases, 58 specimens of normal oral cavity mucosa and of 16 tumour positive lymph nodes taken from the same patients, uPA and PAI-1 antigen were determined by highly sensitive enzyme-linked immunosorbent assays (ELISA). A correlation was found between uPA and PAI-1 in tumour tissue, when compared with the normal mucosa of the same oral cavity. Median levels showed significant elevations in cancer tissue and in tumour positive lymph nodes versus normal oral mucosa. In patients with high levels of uPA or PAI-1, there were significantly more tumour relapses. There was no significant correlation between pathological TNM categories, grading, residual tumour category, tumour site and patient age. In summary, tumour uPA/PAI-1 content (as determined by ELISA) appears to be a strong independent prognostic factor for relapse-free survival in squamous cell cancer of the oral cavity. These observations might help to select patients with poor prognosis for additional adjuvant therapy in conjunction with complete surgical resection.     

Laserinduced Fluorescence Spectroscopy for Real-Time Tissue Differentiation

Background and Objective: Laser-induced fluorescence spectroscopy (LIF) is an important tool for cancer diagnostics. The aim of the study was to examine whether the comparison of laser-induced spectral characteristics, analysed by a specially designed algorithm, allows an identification of bacteria and of human tissue and furthermore even a determination of tissue in respect of dignity.Study design/Material and Methods: A 337.1 nm nitrogen laser with a 600 m fibre optic was used as light source to induce fluorescence in bacteria and human normal and pathological tissues (ovary, esophagus and kidney). Fluorescence spectra were obtained by means of a spectrograph and a CCD-detector and analysed by a computer-aided programme. A total of 251 measurements was performed (pulse repetition rate: 30 Hz; pulse duration: 0.5 ns). Based on an algorithm, two types of tissue were opposed to eachother, and a test was established for comparison of several samples to a reference.Results: With a reproducibility of 100% tissues of different origin could be distinguished. Moreover, differentiation of benign and malignant tissues was possible. Test sensitivity lay above 80%.Conclusions: The results of this pilot study show that this method of laser-induced spectroscopy might be applicable for discrimination of benign and malignant human tissue. Further examinations are needed to verify the in-vivo practicability of this method and to explain the role and presence of endogenous fluorophores.     

Current status of laser applications in oral and cranio-maxillofacial surgery

In oral and cranio-maxillofacial surgery, laser systems are of interest which allow ablation of soft and hard tissues. From the results of recent studies it may be concluded that clinical use of a 9.6 μm CO₂ laser as a cutting tool can be considered to preserve tissue with almost no adverse effects at the light microscopic level. In oral soft tissue surgery, as an alternative to the scalpel, the CO₂ laser is an established procedure which has been in use for more than 25 years. Moreover, many other laser applications have become state of the art over the past years, especially in cancer surgery, in aesthetic indications, in surgery of blood vessels and nerves and in oral surgery. This article is a comprehensive review of recent laser applications in oral and maxillofacial surgery, providing information for dentists, oral surgeons and maxillofacial surgeons. However, in many indications, new studies are required to evaluate if laser treatment is more of value than the conventional surgical technique.     

Quantitative assessment of glucose metabolism in the vessel wall of abdominal aortic aneurysms: correlation with histology and role of partial volume correction

Inflammatory-proteolytic processes in the vessel wall are essential in the pathophysiology of abdominal aortic aneurysm (AAA). It has been demonstrated that, ¹⁸F-FDG-PET/CT may be useful for detection of pathological wall metabolism and therefore risk stratification. Quantification of the FDG-uptake in AAA wall is hampered by partial-volume (PV)-effects. For correction and accurate quantitative ¹⁸F-FDG-uptake analysis we designed and validated a novel IDL-based software in correlation to phantom studies, histopathology and clinical presentation of AAA patients. For in vivo studies 23 patients with symptomatic and asymptomatic AAA underwent ¹⁸F-FDG-PET/CT before surgery. In areas with ¹⁸F-FDG-uptake the maximum and mean standardized uptake values in the vessel wall with (PVC-SUV_max, PVC-SUV_mean) and without (SUV_max, SUV_mean) PV-correction were determined. Results were correlated with clinical presentation, corresponding macrophage-infiltration and MMP-2- and -9-expression in surgical specimens. In patients, SUV_max, SUV_mean as well as PVC-SUV_max or PVC-SUV_mean enabled a highly significant (p < 0.005) discrimination of symptomatic and asymptomatic AAA. Uncorrected and corrected SUVs showed comparable correlations with macrophage-infiltration and MMP-9 expression. No correlation of ¹⁸F-FDG-uptake and MMP-2 was found. In vivo correlations of detected FDG-uptake with clinical and histological results showed comparable results for corrected and uncorrected SUVs. PV-correction is not mandatory for qualitative clinical assessment of glucose metabolism in the vessel wall of AAA-patients but may be necessary to establish quantitative cut off values to stratify patients for aneurysm repair.     

Microstructured dental implants and palatal mucosal grafts in cleft patients: a retrospective analysis.

BACKGROUND: In cleft patients, implant dentistry has become an integral part of oral rehabilitation. However, a lack of keratinized mucosa is found in many cases which may have adverse effects on the long-term success of dental implants with microstructured surfaces. Therefore, the aim of this study was to evaluate whether mucogingival surgery is of value in the treatment of these patients. PATIENTS: Between 1991 and 2002, a total of 35 microstructured dental implants were inserted in 32 cleft patients. In 18 patients, vestibular scars extended to the rim of the marginal mucosa of the implants and the gingiva of the adjacent teeth. To enhance the soft tissue condition, mucogingival surgery was performed using palatal mucosal grafts. METHODS: In May 2002, 29 implants and 16 mucosal grafts were evaluated. Assessment included radiological and clinical parameters. RESULTS: Three implants were lost. Most mucosal grafts showed shrinkage of up to 30%. Clinical and radiological parameters, however, showed results that were very similar to those from non-cleft patients. CONCLUSION: These results support the hypothesis that keratinized mucosal grafts show long-term success in the cleft region as well. Moreover, it may be concluded that a combination of dental implants with a rough surface and palatal mucosal grafts can be recommended for oral rehabilitation of cleft patients.     

Peri-implant care with the CO2 laser: In vitro and in vivo results

Background: Numerous applications for dental lasers have been proposed for both clinical use and experimental purposes. A new indication might be the sterilization of exposed implant surfaces in order to rehabilitate ailing implants. The purposes of this study were to assess CO₂ laser parameters for the decontamination process in vitro and to evaluate the method in vivo.Methods: In vitro, temperature changes at the bone–titanium implant interface were recorded during use of a CO₂ laser-scanning system (Swiftlase^®) and the effects of laser irradiation on titanium implants were examined. In vivo, in 6 beagle dogs, a total of 60 implants and bony defects were treated either conventionally by air-powder-abrasive or by laser irradiation or in combination to evaluate if reosseointegration can occur. In 16 patients (41 ailing implants), the reliability of the CO₂ laser-assisted vs. conventional decontamination was tested.Results: Depending on the parameters chosen, melting and other surface alterations could be seen in vitro. In continuous wave mode, mean power output of 2.5 W for a maximum of 10 s is suitable for the decontamination process. In the beagle dog model, histologic examination revealed new direct bone-to-implant contact following laser-assisted therapy. The clinical study showed 4 months after therapy that laser-decontaminated implants and soft tissue resection resulted in statistically significant better radiographic parameters than conventional decontamination plus soft tissue resection.Conclusions: From these results it was concluded that treatment of peri-implantitis can be optimized using CO₂ laser-assisted implant decontamination. Nevertheless, further studies are required in this field.

Zusammenfassung

Einleitung: In den letzten Jahren wurde eine zunehmende Zahl von Indikationen für den Einsatz von Dentallasern genannt. Eine neue Anwendung könnte in der Dekontamination freiliegender Implantatoberflächen bestehen. Ziel dieser Untersuchungen war, geeignete Laserparameter in vitro und in vivo zu identifizieren und die Methode am Patienten zu überprüfen.Material und Methode: In vitro wurden die Temperaturanstiege am Titan-Knochen-Interface während CO₂ Laser-Bestrahlung unter Verwendung eines Scanners gemessen und die Auswirkungen auf die Implantatmorphologie untersucht. In einer tierexperimentellen Studie wurden insgesamt 60 periimplantäre Defekte konventionell, durch Laserbestrahlung bzw. in Kombination therapiert und histologisch untersucht, inwieweit knöcherne Reappositionen möglich sind. Ziel einer klinischen Studie an 16 Patienten bzw. 41 Implantaten war es, die Laser-gestützte Dekontamination im Vergleich zum konventionellen Vorgehen zu evaluieren.Ergebnisse: Abhängig von den Parametern waren Aufschmelzungen der Implantatoberfläche zu erkennen. Im cw-Betrieb waren dagegen mittlere Leistungen bis zu 2,5 W für bis zu 10 s Bestrahlungszeit applizierbar, ohne die kritische Temperatur am Interface zu überschreiten. Im Tiermodell zeigten sich nach 4 Monaten knöcherne Reappositionen an vormals kontaminierten Implantatoberflächen. In einer klinischen 3-Jahres-Studie waren nach Lasertherapie bessere röntgenologische Parameter nachweisbar als nach konventioneller Dekontamination.Konklusion: Aufgrund dieser Ergebnisse wurde die Schlussfolgerung gezogen, dass die CO₂-Laser-assistierte Implantatdekontamination die Therapie periimplantärer Entzündungen optimieren kann. Weitere Studien sind erforderlich, um ein gesichertes Behandlungsprotokoll für die Periimplantitistherapie erstellen zu können.     

Production of nitric oxide and superoxide by activated macrophages and killing of Leishmania major

Murine macrophages can be activated to produce nitric oxide (NO) and superoxide and these two radicals can react to form peroxynitrite, a powerful oxidant which may be involved in parasite killing. We now show that murine macrophages activated with zymosan and interferon-γ (ZYM/IFN-γ) produced both superoxide (peaking 1–2 h after stimulation, then rapidly declining) and NO (barely detectable at 6 h, peaking by 24 h). Macrophages activated with ZYM alone produced only superoxide, while stimulation with lipopolysaccharide (LPS) and IFN-γ induced NO but not superoxide. Cells stimulated with ZYM/IFN-γ or LPS/IFN-γ killed Leishmania major to a similar degree, an effect that was completely blocked by the addition of N-iminoethyl-L -ornithine. However, macrophages stimulated with ZYM alone were unable to kill L. major. S-nitroso-acetyl-penicillamine, which release NO, was highly leishmanicidal when added directly to the parasites. 3-morpholino-sydnonimine hydrochloride which releases both NO and superoxide simultaneously, was also efficient at killing L. major and this cytotoxicity was greatly enhanced by the addition of superoxide dismutase. Finally, authentic peroxynitrite failed to induce any cytotoxic effect, even at a high concentration. Thus macrophages can produce either NO, superoxide or both, depending on the stimulus. However, the killing of L. major is dependent only on the production of NO.