Analysis of titanium dental implants after failure of osseointegration: combined histological, electron microscopy, and X-ray photoelectron spectroscopy approach.

A multitechnique approach has been used to characterize the surface of nonosseointegrated titanium implants and the surrounding biological tissues. Five pure titanium dental implants were used as reference, and 25 removed implants were studied. Surface and in-depth chemical compositions of the implants (from a total of 16 patients) were investigated by X-ray photoelectron spectroscopy (XPS). Histological slides of the surrounding tissues were examined by light microscopy, XPS, and electron microprobe analysis. None of the failed implants presented the regular surface composition and depth profile of the TiO2 overlayer; foreign elements (Ca, Na, P, Si, Cl, Zn, Pb, and Al) were observed on some implants. Fibrosis, lymphocytic and plasmocytic infiltrates, and granulomatous lesions were detected in the surrounding tissues. XPS and electron microprobe analysis indicated the presence of Zn, Fe, Sn, and Ti in the tissues. As a possible scenario for implant failure, we propose and discuss a oxidoreduction mechanism, leading to a partial dissolution or the complete dissociation of the protective titanium dioxide overlayer and to ion diffusion through the surrounding tissues.

Adenocarcinoma of the fallopian tube: results of a multi-institutional retrospective analysis of 72 patients.

PURPOSE/OBJECTIVE: To determine the prognostic factors for predicting outcome of patients with adenocarcinoma of the fallopian tube and to evaluate the impact of treatment modalities in managing this uncommon disease. MATERIALS AND METHODS: A retrospective analysis of the tumor registries from 6 major medical centers from January 1, 1960 up to March 31, 1995 yielded 72 patients with primary adenocarcinoma of the fallopian tube. The Dodson modification of the FIGO surgical staging as it applies to carcinoma of the fallopian tube was utilized. Endpoints for outcome included overall and disease-free survival. Univariate analysis of host, tumor, and treatment factors was performed to determine prognostic significance, and patterns of failure were reviewed. RESULTS: The median age of the study cohort was 61 years (range 30-79 years). Stage distribution was 24 (33%) Stage I; 20 (28%) Stage II; 24 (33%) Stage III; and 4 (6%) Stage IV. Adjuvant chemotherapy was administered to 54 (75%) patients, and postoperative radiotherapy was employed in 22 (31%). In the latter treatment group, 14 (64%) had whole pelvic external beam irradiation, 5 (23%) whole abdominal radiotherapy, 2 (9%) P-32 instillation, and 1 (4%) vaginal brachytherapy alone. Chemotherapy was used in 67% of Stage I and in 79% of Stages II/III/IV disease (not significant); radiotherapy was more commonly employed in Stage I than in Stages II/III/IV (46% vs. 23%, p = 0.05). The 5-, 8-, 15-year overall and disease-free survival for the study patients were 44.7%, 23.8%, 18.8% and 27.3%, 17%, 14%, respectively. Significant prognostic factors of overall survival included Stage I vs. II/III/IV (p = 0.04) and age < or = 60 years vs. > 60 years at diagnosis (p = 0.03). Only Stage I vs. II/III/IV (p = 0.05) was predictive of disease-free survival. Patterns of failure included 18% pelvic, 36% upper abdominal, and 19% distant. For all patients, upper abdominal failures were more frequently found in Stages II/III/IV (29%) than in Stage I (7%) (p = 0.03). Relapses solely outside of what would be included in standard whole abdominal radiotherapy portals occurred for only 15% of patients (6 of 40) with failures. Furthermore, patients having any recurrence, including the upper abdomen, were more likely (p = 0.001) to die (45%) than those without any type of relapse (18%). CONCLUSION: This retrospective, multi-institutional study demonstrated the importance of FIGO stage in predicting the overall and disease-free survival of patients with carcinoma of the fallopian tube. Future investigations should consider exploring whole abdominal irradiation as adjunctive therapy, particularly in Stage II and higher.

Diaspirin crosslinked hemoglobin (DCLHb): absence of increased free radical generation following administration in a rabbit model of renal ischemia and reperfusion.

In control rabbits, a renal ischemia of 60 min followed by 10 min of reperfusion resulted in an enhanced free radical production in cortical tissue, as assessed by a significant decrease of free glutathione (42%), protein-bound GSH (17%), and vitamin E (49%). In contrast, catalase or glutathione peroxidase activities were not affected by these experimental conditions. Free radical production in this model was also measured directly using electron spin resonance (ESR) spectroscopy associated with a PBN (alpha-phenyl N-tert-butyl-nitrone) spin trap agent in the venous blood arising from the ischemic kidney. The signal consisted of a triplet of doublets. In contrast, no signal could be detected in control blood samples taken prior to inducing ischemia. The burst of free radical production occurred in the early phase after restoration of flow in the kidneys rendered ischemic, as evidenced by a signal of weak intensity which generally appeared within the third minute after reperfusion and progressively increased to form a well-defined asymmetric signal following 10 min of reperfusion. The precise nature of free radicals trapped by the PBN agent remains, however, to be elucidated, but analysis of the coupling constants (aN = 14.5-15 G; a beta H = 2.5-3 G) and asymmetry of the central doublets suggests that the ESR signal may arise from a nitorxy-radical adduct resulting from the spin trapping by PBN of both oxygen- or carbon-centered radicals of lipid origin. As evidenced by both direct and indirect measurements, exchange of rabbit blood immediately after inducing renal ischemia with 30 ml/kg of Diaspirin Crosslinked Hemoglobin (7.5 g/dl in lactated electrolyte) or human serum albumin (7.5 g/dl in lactated electrolyte) did not exacerbate free radical production mediated by an ischemia reperfusion phenomenon, a typical situation found in a resuscitation setting.

Histopathology and ultrastructure of the thymus in OP/OP rats with special focus on thymic macrophages. Effect of bone marrow transplantation.

The thymi of op/op rats were investigated before and after bone marrow graft. Normal littermates were used as controls. The thymic involution and atrophy in non-treated op/op rats was characterized by the presence of pyknotic thymocytes (apoptosis) and numerous lipid-laden macrophages containing pleiomorphic lysosomes. This thymic atrophy is histologically very similar to the thymic involution induced by glucocorticoids or by stress in normal rats. In treated new born op/op rats, the osteopetrotic process began to be reversed 2 weeks after the graft. The thymus of treated op/op recovered a normal weight and its histology and ultrastructure were quite similar to that of normal littermates. These findings are discussed in relation to the defective macrophage function and cellular immunity impairment reported in osteopetrosis.

[Direct approach for demonstrating free radical phenomena during equine postanesthetic myopathy: preliminary study]. / Approche directe pour la mise en évidence des phénomènes radicalaires lors de myopathie postanesthésique équine: étude préliminaire.

This preliminary study demonstrated the existence of a free radical generation during an experimental postischemic muscular reperfusion in a halothane anesthetized horse. The authors used alpha-phényl-N-tert-butylnitrone as a spin trap agent and the electronic paramagnetic resonance method to observe in vivo a free radical generation.

Technique for ventricular wrapping in experimental dynamic cardiomyoplasty.

Cardiomyoplasty is a wrapping of an electrostimulated latissimus dorsi muscle flap around the heart for substitution and/or reinforcement. The surgical technique for reproducible cardiomyoplasties in the goat model is presented. The methods combine the direction of wrapping (clockwise, counter-clockwise) and the orientation of muscle fibers. A cardiomyoplasty model using right and left latissimus dorsi or left latissimus dorsi and pectoralis major as well as a split muscle technique are illustrated.

Experimental odontomas in osteopetrotic op/op rats.

Osteopetrosis is an autosomal recessive disease in several mammalian species. Osteopetrotic op/op rats suffer from complete failure of tooth eruption related to reduced bone resorption. In our earlier studies, op/op rats grafted with bone marrow cells 3 days after birth were cured of the disease and their molar eruption was restored. However, the incisors failed to erupt and their proliferating ends were distorted, forming odontomas. The purpose of the present investigation was to study the odontogenic tissues in the odontomas, using the correlated techniques of radiography and microradiography of undecalcified material, together with histology of decalcified material and scanning electron microscopy.

Monocytic origin of fibrosis. In vitro transformation of HLA-DR monocytes into neo-fibroblasts: inhibitory effect of all-trans retinoic acid on this process.

We report here the spontaneous in vitro transformation of blood monocytes into fibroblasts in a patient who developed pulmonary fibrosis following ciclosporin-mediated immunosuppression, necessitated by heart transplantation. The blood monocytes with this capacity expressed HLA-DR specificity. Monocytes/macrophages were identified by immunofluorescence using monoclonal antibodies against a specific monocyte/macrophage antigen, while the neo-fibroblasts were identified by electron microscopy and immunofluorescence using monoclonal antibodies against a cytoplasmic enzyme specifically involved in the synthesis of collagen. The secretion of collagen was demonstrated using antibodies against collagen. Both the monocytes/macrophages and the neo-fibroblasts express macrophage and fibroblast markers and are able to synthesize collagen. The all-trans retinoic acid derivative (all-trans RA) inhibits this in vitro transformation of HLA-DR monocytes/macrophages into neo-fibroblasts. Therefore, the possible therapeutic role of all-trans RA in controlling the development of fibrosis remains open to investigation. Until now, no efficient therapy is known for fibrotic diseases which are often lethal when affecting the lungs.

Immune cell defects affect bone remodelling in osteopetrotic op/op mice.

The aim of the present work was to further characterize immunological defects in osteopetrosis. The op/op mutant mouse is of particular interest since a marrow cavity develops spontaneously in older animals. The interleukin production (IL-1, IL-2, IL-3, IL-4, IL-6), the presence of macrophage differentiation antigens and the evolution of the bone lesions were studied in osteopetrotic and normal mice. Low levels of IL-1, IL-3 and IL-4 were observed at the age of 6 weeks in the op/op mice. However, at 22 weeks of age, the level of IL-1 and IL-4 returned to normal value in these op/op mice whereas the level of IL-3 remained partially decreased at the same age. Furthermore, macrophage expression of MAC-2 antigen, reduced at 12 weeks of age was found to be normal 10 weeks later. These immunological defects and their recovery seems to be concomitant with the healing of the bone lesions.

In vivo free radical production after cross-clamping and reperfusion of the renal artery in the rabbit.

Postischaemic reperfusion injury is often attributed to the generation of oxygenated free radicals which may subsequently promote lipid peroxidation in cell membranes. Electron paramagnetic resonance spectroscopy in association with the spin trap molecule alpha-phenyl-N-tert-butyl-nitrone allowed direct confirmation of lipid free radical production after renal ischaemia-reperfusion in an in vivo rabbit model. A 60-min period of ischaemia followed by reperfusion caused free radical production twofold greater than after 15 min of ischaemia. Glutathione and alpha-tocopherol have been measured in renal tissue, as indirect markers of lipid peroxidation. After 15 min of ischaemia followed by 10 min of reperfusion, the mean(s.e.m.) glutathione content of the ischaemic kidney was slightly but significantly reduced by 11.9(2.5)% (P < 0.003). The content of alpha-tocopherol was unchanged. However, 10 min of reperfusion following 60 min of ischaemia led to significant decrease in mean(s.e.m.) content of both glutathione (30.4(3.7)%) (2.23(0.2) versus 3.14(0.18) mumol/g wet tissue, P < 0.001) and alpha-tocopherol (46.1(7.8)%) (0.57(0.10) versus 1.09(0.14) micrograms/g wet tissue, P < 0.001) when compared to the control kidney. Under these experimental conditions, desferrioxamine (15 mg/kg administered intravenously before inducing ischaemia), a drug known to limit free radical production, significantly limited the decrease of alpha-tocopherol to 20.8(6.4)% (0.83(0.08) versus 1.05(0.04) micrograms/g wet tissue, P < 0.05), but did not prevent glutathione consumption in the reperfused kidney.

Circulatory and respiratory effects of the combination medetomidine-ketamine in beagles.

The cardiovascular and respiratory parameters of eight laboratory beagles were measured before and after the simultaneous injection of medetomidine (40 micrograms/kg bw) and ketamine (5 mg/bg bw). This combination produced a significant alteration in cardiovascular function. The heart rate, the stroke volume and cardiac output decreased while the systemic vascular resistance increased. These effects were attributed principally to the alpha 2 agonist compound combined with the moderate stimulatory effect of ketamine. The respiratory parameters were little affected by this protocol.

Surgical technique for cardiomyoplasty and iterative transthoracic biopsies in an experimental goat model.

Cardiomyoplasty is a new surgical procedure using transformed skeletal muscle to reinforce or substitute for the myocardium. For the purpose of studying surgical technique and investigating basic questions, we have developed a model of reinforcement cardiomyoplasty. Herein, we describe anesthetic management, surgical technique, and the technique for iterative transthoracic biopsies. This model has proven to be valuable in several long-term studies involving more than 30 goats. Preliminary data to ascertain the efficacy of the proposed technique are provided.

Microradiography and light microscopy of mineralization in the pulp of undemineralized human primary molars.

This study was undertaken to investigate the prevalence, location and histologic features of the different types of mineralization observed in the pulp of human primary molars. Microradiography and light microscopy of undemineralized material disclosed that 95% of primary molars contain pulp calcifications. Histologically, their structure may be classified into four different types: (1) pulp stones, (2) diffuse calcifications, (3) eburnoid tissue and (4) spherulitic calcifications.

Doppler evaluation of left ventricular filling: effect of verapamil on non-obstructive hypertrophic cardiomyopathy.

Impaired left ventricular (LV) filling is known to be a major determinant of non-obstructive hypertrophic cardiomyopathy (HCM). Seventeen patients with non-obstructive HCM (mean age 71 years) were investigated by Doppler echocardiography, before and after oral treatment with verapamil (mean daily doses: 335 mg). Diagnosis was based on clinical and echocardiographic data. Mitral regurgitation was absent or mild. Heart rate, PQ interval and mitral regurgitation did not change after treatment. All calculated values of Doppler LV filling improved significantly: corrected relaxation time, ratio of atrial to early velocity, EF slope and pressure half-time (P less than 0.005) showed more significant differences than more sophisticated indices using time-velocity integrals of Doppler LV filling flow (P less than 0.005). Results appear to reflect an effect of verapamil on LV relaxation; a slight effect of a modified load was nevertheless not excluded. We conclude that all parameters of Doppler LV filling show marked improvement in this elderly group with non-obstructive HCM, after oral verapamil. Doppler echocardiography is an easy and useful clinical method to assess the effect of a drug on ventricular relaxation of non-obstructive HCM.

Evidence of in vivo free radical generation by spin trapping with alpha-phenyl N-tert-butyl nitrone during ischemia/reperfusion in rabbit kidneys.

By using alpha-phenyl N-tert-butyl nitrone (PBN) as spin trap molecule and the electron paramagnetic resonance (EPR) technique, we obtained the first direct evidence of in vivo intervention of free radicals during an ischemia (50 minutes) reperfusion phenomenon in kidney of an intact rabbit. An EPR signal (triplet of doublets) characterized by coupling constants aN = 14.75-15 G and aH beta = 2.5-3 G was detected in blood samples. The signal was consistent with a nitroxyl-radical adduct resulting from the spin trapping by PBN of either oxygen-or carbon-centered radicals. Control experiments indicated that the EPR signal was not due to a toxic effect of the spin trap molecule.

Brushite in the pulp of primary molars.

This study was undertaken to investigate the mineral phase of spherulitic calcifications discovered in the pulpous mesenchyme of human primary molars by microradiography. Analytical scanning electron microscopy and x-ray diffraction disclosed that well-crystallized brushite is the major compound of the spherulites. The mechanism leading to the crystallization of brushite is far from well understood. Histologically, on decalcified sections, inflammatory cells and capillaries can be seen trapped in the spherulites. In the light of these findings, it could be suggested that metabolic conditions may promote the crystallization of brushite in the pulp of primary molars.

Effects of bone marrow transplantation on impacted dental germs in osteopetrotic op/op rats.

The osteopetrotic op/op rats suffered from a complete failure of tooth eruption in association with a reduced bone resorption. An unresorbed occlusal bone overlaid the germs which remained embedded in bone. The process of prefunctional eruption in limited growing teeth depends on the resorption of the alveolar bone covering the germs. The aim of this study was to investigate the effects of hematopoïetic grafts in newborn op/op rats on the process of prefunctional eruption. Fifteen op/op treated rats were used for radiographic, microradiographic and histologic examinations. After transfusion of bone marrow cells, we observed the restoration of bone resorption and a delayed eruption of the molars. The incisors never erupted. They developed odontome-like tumors near their apices. These results confirm the dependence of tooth eruption on bone resorption.

[Ultrastructure of microcalcifications of the pulp mesenchyme of human deciduous teeth]. / Ultrastructure des microcalcifications du mésenchyme pulpaire des dents temporaires humaines.

Scanning electron microscopic observations of pulp calcifications in deciduous molars were correlated with microradiographic findings. Numerous spherical calcifications were found in appearance similar to those in the permanent dentition. In a second type, mineralization took the form of diffuse deposits of calcium. The discrete diffuse foci coalesced into large islands of mineralized connective tissue. A third type of calcification was observed in which rhombic crystals were associated in a spherulitic pattern. The exact cause of the crystal formation is unknown. Moreover, as we are aware, the spherulitic calcifications have never been previously reported in this location. The preliminary results indicated that mineralization in the pulp of deciduous molars, takes a variety of forms, suggesting that calcium deposition can occur by different processes.