Dentofacial rehabilitation by osteodistraction, augmentation and implantation despite osteogenesis imperfecta.

Osteogenesis imperfecta-- a heritable systemic disorder characterized by enhanced bone fragility-- is frequently associated with a Class III malocclusion and distinct dental disorders. This patient, suffering from a late form of osteogenesis imperfecta, displayed early loss of teeth and severe maxillary hypoplasia. Bone grafting of the alveolar ridge was assumed not to guarantee a neutral basal relation before dental implantation. Due to the risk of atypical fractures conventional orthognathic surgery was excluded in the atrophic maxilla. In contrast to a conventional Le Fort I osteotomy, osteodistraction of the maxilla can be performed omitting the precarious down-fracture procedure. Despite a lack of reports on this technique in patients with osteogenesis imperfecta, dysgnathia was corrected by osteodistraction of the upper jaw. The loss of teeth was treated by augmentation of the alveolar crest using autogenous bone from the iliac crest followed by placement of dental implants. Stable normocclusion of the implant-supported overdentures was achieved without any detectable relapse over 4 years. For the first time it has been demonstrated that advanced surgical techniques like osteodistraction, alveolar crest augmentation and dental implantation can successfully be combined for dentofacial rehabilitation even in patients suffering from osteogenesis imperfecta.

Possibilities and limitations of current stereo-endoscopy.

BACKGROUND: Stereo-endoscopy has become a commonly used technology. In many comparative studies striking advantages of stereo-endoscopy over two-dimensional presentation could not be proven. To show the potential and fields for further improvement of this technology is the aim of this article. METHOD: The physiological basis of three-dimensional vision limitations of current stereo-endoscopes is discussed and fields for further research are indicated. New developments in spatial picture acquisition and spatial picture presentation are discussed. RESULTS: Current limitations of stereo-endoscopy that prevent a better ranking in comparative studies with two-dimensional presentation are mainly based on insufficient picture acquisition. CONCLUSION: Devices for three-dimensional picture presentation are at a more advanced developmental stage than devices for three-dimensional picture acquisition. Further research should emphasize the development of new devices for three-dimensional picture acquisition.

[Phylogenetic aspects of lip function]. / Phylogenetische Aspekte der Lippenfunktion.

Lips can be considered a phylogenic summary of nasolabial and facial muscle evolution. They represent the central point of facial morphogenesis. The progressive development of oral and facial functions is an elementary human necessity for feeding, suction, oral competence, swallowing, language, and mimics. Each discontinuity causes functional and anatomic disorders. Any damage to the lips creates facial unbalance. Precise knowledge of lip function is indispensable for optimal reconstruction.

Comparison between three-dimensional presentation of endoscopic procedures with polarization glasses and an autostereoscopic display.

BACKGROUND: Most endoscopic procedures are done with a two-dimensional (2D) view or a spatial presentation with polarization glasses. A new method of presenting three-dimensional (3D) spatial views is the autostereocopic display. We compared the performances of untrained test persons using these methods. METHODS: We designed three tests that had to be performed with one of the presentations. We used a Karl Storz 3D set with a 0 degrees stereooptic and a grasper. The autostereoscopic display was the Dresden 3D display. The 59 test persons were students who had never before worked with endoscopic devices. RESULTS: There were few differences between the tests, and none were statistically significant. The results with 2D were slightly better than those with polarization glasses, and the results with polarization glasses were slightly better than those with the autostereoscopic display. CONCLUSIONS: There are few differences between the procedures. A true spatial view is limited by the similarity of the two half-pictures.

New model for in vivo quantification of microvascular embolization, thrombus formation, and recanalization in composite flaps.

BACKGROUND: Microthrombi are suggested to be involved in the pathogenesis of composite flap failure. Due to the lack of appropriate experimental models, however, the significance of microvascular thrombus formation and microthromboembolization in free flap failure remains poorly understood. The purpose of this study was therefore to develop a rat hindlimb model that allows tissue-confined in vivo analysis of thrombus formation, thromboembolization, and recanalization within the microcirculation of osteomyocutaneous flaps using intravital fluorescence microscopy. MATERIALS AND METHODS: Thrombus formation was induced photochemically in individual arterioles and venules of muscle, subcutis, and periosteum. To study thromboembolization, autologous arterial thrombi (40 microm) were preformed in vitro and were injected into the femoral artery supplying the osteomyocutaneous flap. RESULTS: First platelet deposition was found independent from microvascular red blood cell velocity, while the subsequent growth of thrombus correlated inversely with red blood cell flow measured in the respective microvessel. Time required for complete thrombotic arteriolar occlusion exceeded 700 s, whereas thrombus growth in venules was found to be significantly accelerated ( approximately 300 s) without differences between the individual tissues analyzed. The embolization resulted in a complete shutdown of capillary perfusion in muscle, subcutis, skin, and periosteum. During subsequent spontaneous recanalization, capillary perfusion increased in all tissues to approximately half of baseline, however, without further recovery during the 4-h postembolization period. CONCLUSIONS: The model presented is suitable to quantitatively study the pathophysiology of microvascular thrombus formation, thromboembolization, and recanalization in composite flaps, and may thus be used to evaluate the effectiveness of novel therapeutic strategies to prevent flap failure.

Microvascular transfer-related abrogation of capillary flow motion in critically reperfused composite flaps.

Capillary flow motion is defined as rhythmic fluctuations of blood flow in the capillaries. Although critical perfusion has been demonstrated to induce capillary flow motion, little is known about the role of capillary flow motion in microvascular free flaps. The aim of this study was to elucidate the tissue-confined incidence and consequence of capillary flow motion in microvascularly transferred composite flaps, using intravital fluorescence microscopy. In Wistar rats, transferred osteomyocutaneous flaps (n = 7), which were exposed to 1 h of ischaemia during the anastomotic procedure followed by 1 h of reperfusion, were subjected to critical perfusion by stepwise reduction of the femoral-artery blood flow to 0.15 ml min(-1), 0.10 ml min(-1) and 0.05 ml min(-1). Pedicled osteomyocutaneous flaps that were not subjected to ischaemia (n=8) served as controls. In pedicled flaps critical perfusion induced capillary flow motion in the muscle, but not in the skin, subcutis and periosteum. In these flaps, the functional capillary density was preserved in all tissues analysed, including the skeletal muscle. Additional sympathetic denervation of the pedicled flaps did not change the incidence or pattern of capillary flow motion. In contrast, after flap transfer capillary flow motion in muscle tissue did not occur during critical perfusion. As a consequence, a shutdown of perfusion of individual capillaries was observed, resulting in a significant reduction (P<0.05) in functional capillary density, not only in the subcutis, skin and periosteum but also in the muscle itself. Thus, our data suggest that the microcirculatory control of pedicled osteomyocutaneous flaps is preserved during critical perfusion by skeletal-muscle capillary flow motion, whereas this protective regulatory mechanism is lost during the initial reperfusion period after flap transfer, probably not because of denervation but because of surgery- and/or ischaemia-reperfusion-associated injury.

Reduction of inflammatory response in composite flap transfer by local stress conditioning-induced heat-shock protein 32.

BACKGROUND: The failure of composite flaps despite anastomotic patency is thought to be mediated by the inflammatory response within the microvasculature, which results from unavoidable surgical trauma and transfer-related ischemia-reperfusion. Evidence suggests that stress conditioning may improve flap survival; however, the molecular mechanisms of protection are far from being clear. Therefore, we analyzed whether stress conditioning-induced heat-shock protein 32 is effective to prevent the inflammatory response in transferred osteomyocutaneous flaps. METHODS: In a rat model, leukocyte-endothelial cell interaction and endothelial integrity disruption as early indicators of the inflammatory response were quantitatively analyzed in muscle, subcuticular tissue, and periosteum of microvascularly transferred osteomyocutaneous flaps by using intravital fluorescence microscopy. Twenty-four hours before flap transfer, stress conditioning was induced by local heating of the left hindlimb up to 42.5 degrees C for 30 minutes. In additional animals, stress conditioning-induced activity of heat-shock protein 32 was inhibited by tin protoporphyrin-IX. Unconditioned flaps served as controls. RESULTS: In all tissues analyzed, control flaps showed significant leukocyte adherence in postcapillary venules, increased intercellular adhesion molecule-1 (ICAM-1) expression, and endothelial integrity disruption, but a lack of heat-shock protein 32. In contrast, stress conditioning induced marked heat-shock protein 32 expression, which was associated with a significant reduction (P <.05) of leukocyte adherence, ICAM-1 expression, and endothelial hyperpermeability. The inhibition of heat-shock protein 32 by tin protoporphyrin-IX completely abolished the stress conditioning-induced amelioration of the inflammatory response in all tissues analyzed. CONCLUSIONS: Stress conditioning by local heat-shock priming reduces the inflammatory response in osteomyocutaneous flaps. The protective effect is predominantly mediated by the induction of heat-shock protein 32.

Local heat-shock priming-induced improvement in microvascular perfusion in osteomyocutaneous flaps is mediated by heat-shock protein 32.

BACKGROUND: Stress conditioning is thought to improve microvascular free flap survival but the mechanisms of protection are not clear. The aim of this study was to determine whether local induction of heat-shock protein (HSP) 32 improves microvascular perfusion in transferred osteomyocutaneous flaps. METHODS: The hindlimb harvest region of osteomyocutaneous flaps in Wistar rats was subjected to stress conditioning by local heating (30 min, 42.5 degrees C) 24 h before microvascular flap transfer. In a second group of animals, after heat-shock priming, the action of HSP-32 was inhibited by tin protoporphyrin IX. Animals with unconditioned flaps served as controls. After transfer, the microcirculation of the muscle, cutaneous, subcutaneous and periosteal tissue of the flap was analysed quantitatively for 6 h using intravital fluorescence microscopy. RESULTS: Immunohistochemistry revealed that HSP-32 was detectable only after priming and not in unconditioned flaps. Priming did not alter functional capillary density or capillary red blood cell velocity compared with that in unconditioned flaps. However, heat-shock priming induced significant capillary dilatation (P < 0.05) and thus a substantial increase in capillary blood flow volume (P < 0.05) in all tissues of the transferred flaps. Inhibition of HSP-32 by tin protoporphyrin IX completely abolished the priming-induced improvement in capillary perfusion, as indicated by the lack of increased capillary diameters and volumetric blood flow. CONCLUSION: The present study demonstrated that stress conditioning by local heat-shock priming improves nutritive perfusion in osteomyocutaneous flaps by capillary dilatation, probably mediated through the vasoactive action of HSP-32.

Oral contraceptives and cardiovascular outcomes: cause or bias?

The 1995-1996 "pill" scare, which suggested that third-generation oral contraceptives (OCs) were associated with a greater risk of venous thromboembolism (VTE) than second-generation OCs, had serious social and public health consequences, as women discontinued OCs, resulting in unwanted pregnancies and unnecessary abortions. This article uses the Bradford Hill criteria, for diagnosing causality from an observed association, to interpret evidence from recent studies as to whether there is any difference in the risk of VTE between third- and second-generation OCs. Bias and the influence of confounders have also been examined in relation to the difference in the risk of VTE between third- and second-generation OCs reported in the 1995-1996 studies. It is clear from the results of this analysis that none of the Bradford Hill criteria are fulfilled. Thus, a causal relationship cannot be inferred from the alleged association of third-generation OCs with VTE. Indeed, it would appear that the unavoidable bias in observational research is a more likely explanation for the apparent difference in the risk of VTE between third- and second-generation OCs in the 1995-1996 studies. Recent studies, which employed more appropriate controls for these biases showed no difference in the risk of VTE between third- and second-generation OCs. A Danish study (1994-1996) demonstrated a lower risk of thrombotic morbidity and mortality with third-generation OCs compared with second-generation OCs. In addition, the Transnational study has shown that third-generation OCs have a significantly lower relative risk (0.3 [0.1-0.9]) for acute myocardial infarction (MI) compared with second-generation products. In conclusion, there is no convincing evidence for a difference in the risk of stroke or VTE between third- and second-generation OCs. Moreover, third-generation OCs may be associated with a lower risk of MI than second-generation OCs.

[Roentgen diagnosis in oromaxillofacial surgery]. / Röntgendiagnostik in der Mund-, Kiefer-, Gesichtschirurgie.

A vital X-ray imaging technique in oral and craniomaxillofacial surgery is the panoramic X-ray. Due to its variety of special projections, including imaging of the transversal level and low exposure to radiation, it is suitable for answering many clinical questions and for diagnostics of various findings. It has become possible to minimize the necessary doses by further development of technology and devices, as well as of X-ray films and by new detection systems, such as sensors or screens. In some clinical cases, the diagnostic deficiencies of conventional imaging techniques make computed tomography (CT) and magnetic resonance (MR) imaging indispensable. Although MR is particularly suitable for soft tissue imaging, it has also become helpful in finding cortical changes by shorter measuring times. In certain cases, e.g., changes to bone metabolism, differentiated methods of nuclear medicine make image-aided analysis of function possible.

Recurrent use of newer oral contraceptives and the risk of venous thromboembolism.

The epidemiological studies that assessed the risk of venous thromboembolism (VTE) associated with newer oral contraceptives (OC) did not distinguish between patterns of OC use, namely first-time users, repeaters and switchers. Data from a Transnational case-control study were used to assess the risk of VTE for the latter patterns of use, while accounting for duration of use. Over the period 1993-1996, 551 cases of VTE were identified in Germany and the UK along with 2066 controls. Totals of 128 cases and 650 controls were analysed for repeat use and 135 cases and 622 controls for switching patterns. The adjusted rate ratio of VTE for repeat users of third generation OC was 0.6 (95% CI:0.3-1.2) relative to repeat users of second generation pills, whereas it was 1.3 (95% CI:0.7-2.4) for switchers from second to third generation pills relative to switchers from third to second generation pills. We conclude that second and third generation agents are associated with equivalent risks of VTE when the same agent is used repeatedly after interruption periods or when users are switched between the two generations of pills. These analyses suggest that the higher risk observed for the newer OC in other studies may be the result of inadequate comparisons of pill users with different patterns of pill use.

Are wireless phones safe? A review of the issue.

Most wireless phones and their corresponding base stations operate at a very low power output and in the radiofrequency range of 800 to 2000 Megahertz. Current international guidelines protect against thermal biological effects in terms of the local or whole-body specific absorption rate (SAR). Potential non-thermal bio-effects resulting from the use of wireless phones are not established and laboratory (i.e., in vitro, in vivo) studies have shown conflicting results. Epidemiological studies of potential human health effects are few but are expected to emerge in the near future. Challenges to epidemiological research include difficult exposure assessment, selection of appropriate controls, potential confounding bias, and validation of outcome. Scientists, community advocacy groups, and public health professionals must be equipped to critically analyze the emerging evidence within a benefit/risk assessment framework.

The differential risk of oral contraceptives: the impact of full exposure history.

Previous discussions have indicated that the small increases of risk of venous thromboembolism (VTE) associated with newer combined oral contraceptives (third generation, containing desogestrel and gestodene) may be attributed to bias due to cohort effects. In a case-control analysis, this may produce an overestimate of risk of newer preparations. In 10 centres in Germany and the UK, the Transnational Study analysed data from 502 women aged 16-44 years with VTE, and from 1864 controls matched for 5-year age group and region. Information on lifetime exposure history from all subjects was added to the dataset used in previous analyses and entered into a Cox regression model with time-dependent covariates. Based on 17 622 continuous exposure episodes comprising 47 914 person-years of observation, the adjusted hazard ratio (equivalent to odds ratio, OR) of VTE for the comparison of current users of third-generation versus current users of second-generation (primarily levonorgestrel compounds) combined oral contraceptives was 0.8 (0.5 to 1.3). The OR obtained in standard case-control analysis had been 1.5 (1.1 to 2.1). Adjustment for past exposures includes more information and appears more valid than the standard cross-sectional analysis. Using this approach, the Transnational Study data show no evidence for an increased risk of VTE with third- compared with second-generation combined oral contraceptives.

PIP: This transnational study examined the risk of venous thromboembolism (VTE) associated with combined oral contraceptives (OCs). The study analyzed data on 502 women aged 16-44 years with VTE and 1864 controls from 10 centers in Germany and the UK from 1 January, 1993, to 20 October, 1995. Information on lifetime exposure history from all subjects was added to the data set used in previous analyses and entered into a Cox regression model with time-dependent covariates. Based on 17,622 continuous exposure episodes comprising 47914 person-years of observation, the adjusted hazard ratio of VTE for the comparison of current users of third-generation versus current users of second-generation combined OCs was 0.8 (0.5-1.3). The OR obtained in standard case-control analysis had been 1.5 (1.1-2.1). Adjustment for past exposures includes more information and appears more valid than the standard cross-sectional analysis. Using this approach, the transnational study data show no evidence for an increased risk of VTE with third-generation compared with second-generation combined OCs.

The effects of antirhino- and enteroviral vinylacetylene benzimidazoles on cytochrome P450 function and hepatic porphyrin levels in mice.

In an ongoing effort to identify an orally bioavailable compound for the treatment of rhino- and enteroviral infections, a series of vinylacetylene benzimidazoles was recently examined. Previous studies demonstrated the potential for these compounds to possess both good in vitro antiviral activity as well as acceptable oral plasma concentrations in mice. Optimization of these properties led to four compounds as candidates for further evaluation. In view of the recognized potential for certain acetylenic drugs both to inhibit cytochrome P450 enzymes by mechanism-based inactivation and to possibly perturb heme metabolism, information regarding drug effects on cytochromes P450 and hepatic porphyrin levels was sought. In an initial single-dose pharmacokinetic study, the four selected compounds were given orally to mice, and both plasma concentrations and porphyrin levels were determined. Two of the compounds, 4 and 5, caused a pronounced increase in liver porphyrin levels whereas compounds 6 and 7 exhibited almost no effect on porphyrin levels. Analysis of plasma concentrations showed that only 4 and 5 gave significant exposure and that 6 and 7 produced negligible levels of drug in the plasma even at the highest dose tested (500 mg/kg). A multiple dose study was then initiated in which compounds 4 and 5 were given for 1 week in daily oral doses to mice. Upon completion of dosing, liver was analyzed for cytochrome P450-dependent 7-ethoxyresorufin O-deethylase (EROD) and benzphetamine N-demethylase (BND) activities, total cytochrome P450 content, and porphyrin levels. Both vinylacetylenes showed dose dependent inhibitory and induction effects on EROD and BND activities. In addition, these compounds caused a marked increase in hepatic porphyrin levels. Therefore, while all four selected compounds displayed potent antiviral activity and two of the compounds exhibited acceptable pharmacokinetic properties, the hepatic effects of these latter two compounds suggest the potential for drug induced porphyria with multidose therapeutic use.

In vivo analysis of the microcirculation of osteomyocutaneous flaps using fluorescence microscopy.

Previous studies have indicated that freely transferred osteomyocutaneous flaps may fail despite anastomotic patency. While microvascular dysfunction is thought to be one of the major causes for this type of flap failure, little is known of its underlying mechanisms, probably due to the lack of adequate experimental models allowing detailed intravital microcirculatory analysis. Herein we report quantitative analysis of the microcirculation of periosteum, muscle, subcutis and skin by intravital fluorescence microscopy using an osteomyocutaneous free flap model in the hindlimb of rats. The microcirculation of the different tissues was studied after microanastomotic transfer (free flap), and was compared to that after solely elevating the tissue, mimicking a pedicled osteomyocutaneous flap. Transferred flaps, which were exposed to 1 h of ischaemia during the anastomotic procedure, showed a slight but significant decrease (P< 0.05) of functional capillary density in muscle, subcutis and skin when compared with the microcirculation of pedicled flaps, while capillary diameters, red blood cell velocity and blood flow of perfused capillaries remained almost unaffected. The decrease of functional capillary density was associated by a significant (P< 0.05) inflammatory response, as indicated by the increased number of leukocytes adherent to the endothelial lining of postcapillary venules. While the functional capillary density of periosteum was not affected by the free transfer procedure, the inflammatory response was found similar when compared with that observed in muscle and subcutis. Thus, our study indicates that even after a short 1-h ischaemic time period, capillary perfusion failure and leukocyte-endothelial cell interaction are the main events, characterising microvascular dysfunction after free transfer of osteomyocutaneous flaps. Using the model described herein, intravital microscopic analysis of the microcirculation proved an appropriate tool to study the individual microvascular response after free tissue transfer, and may thus be used to evaluate the effectiveness of novel therapeutic regimens which aim at counteracting microcirculatory dysfunction in free osteomyocutaneous flaps.