Clinical outcomes following a combined vertical and horizontal alveolar ridge augmentation and two-stage implant placement using either autogenous tooth roots or autogenous bone blocks.

AIM: To assess and compare the short-term clinical outcomes following a combined vertical and horizontal alveolar ridge augmentation and two-stage implant placement using either autogenous tooth roots (TR) or autogenous bone blocks (AB). MATERIALS AND METHODS: A total of n = 27 patients (TR/AB: 13/14) exhibiting n = 31 implants (TR/AB: 14/17) were available for the analysis. Each subject had been allocated to a combined vertical and horizontal alveolar ridge augmentation using either (1) healthy TR (e.g., retained wisdom teeth), or (2) monocortical AB harvested from the retromolar area (i.e. external oblique line). Clinical parameters (e.g., bleeding on probing, BOP; probing pocket depth, PD; mucosal recession, MR) were recorded after a follow-up period of 16.03 ± 4.3 months following implant placement. RESULTS: The survival rates amounted to 100% in both groups. TR and AB grafted sites were associated with similar changes in mean BOP (8.97 ± 27.73%; 11.90 ± 18.97%), PD (0.53 ± 0.49; 0.47 ± 0.67 mm), and MR (0.03 ± 0.13; 0.0 ± 0.02 mm) values. The incidence of peri-implant mucositis and peri-implantitis at the patient level amounted to 15.38% and 0.0% in the TR-, and 28.57% and 7.14% in the AB group. CONCLUSIONS: Both surgical procedures were associated with peri-implant tissue health and stability on the short-term.

Effects of methylphenidate on the behavior of male 5xFAD mice.

Alzheimer's disease is a neurodegenerative disorder characterized by a loss of memory and spatial orientation. It is also reported that the dopamine system is affected. Dopamine plays a prominent role in motor functions, motivation, emotion, arousal and reward, and it is important for learning and memory. One model that represents characteristic hallmarks of Alzheimer's disease is the 5xFAD mouse model, in which parenchymal plaque load starts at 2months of age. Transgenic 5xFAD mice show the first behavioral deficits at 6months, which are evident at 9months of age. In this study, we investigated the pharmacological influence of methylphenidate (MPH) on behavioral deficits of 5xFAD mice. Using a battery of behavioral tests, we observed no influence of MPH on anxiety in the elevated plus maze, whereas the locomotion and explorative activity in the open field was increased in transgenic and non-transgenic 5xFAD mice after the application of MPH. Further MPH inhibits habituation in the open field in healthy 5xFAD littermates after the application of 10mg/kg MPH. On the other hand, 10mg/kg MPH improved spatial memory in 6-month-old transgenic 5xFAD males, i.e., at a time point when deficits start to occur. However, in 9-month-old transgenic mice, MPH did not improve persisting learning and memory deficits. We concluded that MPH might improve the non-cognitive, apathy-like behavior (indicated by a reduced exploration), but it has no influence on sustained Alzheimer typical learning and memory deficits.

Behavioral and EEG changes in male 5xFAD mice.

Transgenic animal models of Alzheimer's disease (AD) are widely used to investigate mechanisms of pathophysiology and cognitive dysfunctions. A model with a very early development of parenchymal plaque load at the age of 2months is the 5xFAD mouse (Tg6799, Oakley et al. 2006). These 5xFAD mice over-express both human amyloid precursor protein (APP) and human presenilin 1 (PS1). Mice from this line have a high APP expression correlating with a high burden and an accelerated accumulation of the 42 amino acid species of amyloid-ß (Aß). The aim of this study was the behavioral and functional investigations of 5xFAD males because in most studies females of this strain were characterized. In comparison to literature of transgenic 5xFAD females, transgenic 5xFAD males showed decreased anxiety in the elevated plus maze, reduced locomotion and exploration in the open field and disturbances in learning performance in the Morris water maze starting at 9months of age. Electroencephalogram (EEG) recordings on 6month old transgenic mice revealed a decrease of delta, theta, alpha, beta and gamma frequency bands whereas the subdelta frequency was increased. EEG recordings during sleep showed a reduction of rapid eye movement sleep in relation to the amount of total sleep. Thus, 5xFAD males develop early functional disturbances and subsequently behavioral deficits and therefore they are a good mouse model for studying Alzheimer's disease.

The combination of appetitive and aversive reinforcers and the nature of their interaction during auditory learning.

Learned changes in behavior can be elicited by either appetitive or aversive reinforcers. It is, however, not clear whether the two types of motivation, (approaching appetitive stimuli and avoiding aversive stimuli) drive learning in the same or different ways, nor is their interaction understood in situations where the two types are combined in a single experiment. To investigate this question we have developed a novel learning paradigm for Mongolian gerbils, which not only allows rewards and punishments to be presented in isolation or in combination with each other, but also can use these opposite reinforcers to drive the same learned behavior. Specifically, we studied learning of tone-conditioned hurdle crossing in a shuttle box driven by either an appetitive reinforcer (brain stimulation reward) or an aversive reinforcer (electrical footshock), or by a combination of both. Combination of the two reinforcers potentiated speed of acquisition, led to maximum possible performance, and delayed extinction as compared to either reinforcer alone. Additional experiments, using partial reinforcement protocols and experiments in which one of the reinforcers was omitted after the animals had been previously trained with the combination of both reinforcers, indicated that appetitive and aversive reinforcers operated together but acted in different ways: in this particular experimental context, punishment appeared to be more effective for initial acquisition and reward more effective to maintain a high level of conditioned responses (CRs). The results imply that learning mechanisms in problem solving were maximally effective when the initial punishment of mistakes was combined with the subsequent rewarding of correct performance.

Allosteric enhancement of metabotropic glutamate receptor 5 function promotes spatial memory.

Group I metabotropic glutamate receptors (mGluRs) have been implicated in learning and memory formation. Recent findings indicate an important function of the group I mGluR subtype 5. Here, we used the Y-maze spatial alternation task and examined whether enhancement of intrinsic mGluR5 activity immediately after learning, i.e. during a critical period for memory consolidation, would have any consequences on long-term memory retention in rats. Intracerebroventricular application of the allosteric mGluR5 potentiator DFB (3,3'-difluorobenzaldazine) resulted in a marked improvement in spatial alternation retention when it was tested 24 h after training. The promnesic effect increased with the difficulty of the task and was apparently due to a substantial enhancement of consolidation. The applied dose of DFB did not cause behavioral changes in the open field, and was devoid of structural side-effects as evaluated by immunohistochemical examination. Our results suggest an important function of post-training mGluR5 activation in some types of hippocampus-dependent spatial learning.

Qualitative evaluation of titanium implant integration into bone by diffraction enhanced imaging.

Diffraction enhanced imaging (DEI) uses refraction of x-rays at edges, which allows pronounced visualization of material borders and rejects scattering which often obscures edges and blurs images. Here, the first evidence is presented that, using DEI, a destruction-free evaluation of the quality of integration of metal implants into bone is possible. Experiments were performed in rabbits and sheep with model implants to investigate the option for DEI as a tool in implant research. The results obtained from DEI were compared to conventional histology obtained from the specimens. DE images allow the identification of the quality of ingrowth of bone into the hydroxyapatite layer of the implant. Incomplete integration of the implant with a remaining gap of less than 0.3 mm caused the presence of a highly refractive edge at the implant/bone border. In contrast, implants with bone fully grown onto the surface did not display a refractive signal. Therefore, the refractive signal could be utilized to diagnose implant healing and/or loosening.

Osteointegration of hydroxyapatite-titanium implants coated with nonglycosylated recombinant human bone morphogenetic protein-2 (BMP-2) in aged sheep.

Osteointegration of metal implants into aged organisms can be severely compromised due to reduced healing capacity of bone, lack of precursor cells for new bone formation, or osteoporosis. Here, we report on successful implant healing in a novel model of aged sheep in the presence of nonglycosylated bone morphogenetic protein 2 (BMP-2). Ewes of 8 to 12 years with significant radiologic and histologic signs of osteoporosis and adipocytic bone marrow received a cylindrical hydroxyapatite-titanium implant of 12 x 10 mm. BMP-2 has been produced as a bacterial recombinant fusion protein with maltose-binding protein and in vitro generation of mature BMP-2 by renaturation and proteolytic cleavage. A BMP-2 inhibition ELISA was developed to measure the in vitro release kinetics of bioactive human BMP-2 from immersed solid implant materials by using Escherichia coli expressed and biotinylated recombinant human BMP-2 receptor IA extracellular domain (ALK-3 ECD). The implants were placed laterally below both tibial plateaus, with the left leg implant carrying 380 microg BMP-2. Both implant types became integrated within the following 20 weeks. The control implant only integrated at the cortical bone, and little new bone formation was found within the pre-existing trabecular bone or the marrow cavity. Marrow fat tissue was partially replaced by unspecific connective tissue. In contrast, BMP-2-coated implants initiated significant new bone formation, initially in trabecular arrangements to be replaced by cortical-like bone after 20 weeks. The new bone was oriented towards the cylinder. Highly viable bone marrow appeared and filled the lacunar structures of the new bone. In mechanical tests, the BMP-2-coated implants displayed in average 50% higher stability. This animal model provided first evidence that application of nonglycosylated BMP-2 coated on solid implants may foster bone healing and regeneration even in aged-compromised individuals.

Interleukin-6: a cytokine to forget.

It is known that proinflammatory cytokines such as interleukin-6 (IL-6) are expressed in the central nervous system (CNS) during disease conditions and affect several brain functions including memory and learning. In contrast to these effects observed during pathological conditions, here we describe a physiological function of IL-6 in the "healthy" brain in synaptic plasticity and memory consolidation. During long-term potentiation (LTP) in vitro and in freely moving rats, IL-6 gene expression in the hippocampus was substantially increased. This increase was long lasting, specific to potentiation, and was prevented by inhibition of N-methyl-D-aspartate receptors with (+/-)-2-amino-5-phosphonopentanoic acid (AP-5). Blockade of endogenous IL-6 by application of a neutralizing anti-IL-6 antibody 90 min after tetanus caused a remarkable prolongation of LTP. Consistently, blockade of endogenous IL-6, 90 min after hippocampus-dependent spatial alternation learning resulted in a significant improvement of long-term memory. In view of the suggested role of LTP in memory formation, these data implicate IL-6 in the mechanisms controlling the kinetics and amount of information storage.

Clonal identity of Candida albicans in the oral cavity and the gastrointestinal tract of pre-school children.

The clonal relationship between oral and fecal Candida albicans isolated from children of pre-school age was examined using RAPD analysis. Significantly higher levels of C. albicans were found in saliva, dental plaque, carious specimens and stools of 56 patients with severe caries as compared to 52 healthy control subjects. The highest prevalence was found in carious specimens and a strong correlation was observed between its presence in saliva, dental plaque, carious specimen and feces. RAPD analysis of isolates from 23 patients with simultaneous oral and fecal C. albicans revealed clonal counterparts present in both oral and stool samples in 15 cases; five patients harbored closely related strains; and three patients harbored unrelated strains. Our results demonstrate a strong correlation between oral and gastrointestinal C. albicans colonization. We assume that carious teeth may constitute an ecologic niche for C. albicans potentially responsible for recurrent oral and non-oral candidiasis.

Inhibition of mGluR5 blocks hippocampal LTP in vivo and spatial learning in rats.

Particular subtypes of metabotropic glutamate receptors (mGluRs) have been shown to be specifically involved in certain types of long-term synaptic plasticity and learning. We examined whether inhibition of mGluR5 by the specific noncompetitive antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP) has any functional consequences on long-term potentiation in the dentate gyrus in vivo and on learning of a spatial alternation task. Intracerebroventricular application of 13.8 microg MPEP 30 min before tetanization resulted in a rapid decline of potentiation during the first 7 min and a significantly lower potentiation of the MPEP group as compared to controls. The same dose of the antagonist given 30 min before training of a Y-maze spatial alternation task caused a marked impairment of retention tested 24 h later. In contrast, MPEP had virtually no effects on retention if injected immediately after the training session. Our findings suggest an important function of mGluR5 during the initiation of synaptic plasticity and memory formation.

Orofacial findings in the Klippel-Trénaunay syndrome.

The Klippel-Trénaunay syndrome is a triad of congenital anomalies characterised by haemangiomas, varicosities, and unilateral bony and soft tissue hypertrophy. Hypertrophy usually affects one distal limb, but trunk or face may be affected. Cutaneous haemangiomas (nevus flammeus) of varying extent and irregular contour are often present in the hypertrophic regions. Varicosities may also be part of the vascular lesions of the syndrome. Orofacial manifestations include facial asymmetry, jaw enlargement, and malocclusions as well as premature tooth eruption. Two cases of the Klippel-Trénaunay syndrome are presented here. Both of these show the typical hemifacial hypertrophy and premature eruption of teeth on the affected side. In the first case only the left mandibular region was affected. In contrast, in the second there was hypertrophy of the whole left side of the body including upper and lower jaws. This boy also suffers from congenital ideokinetic retardation, while the first was otherwise normal. Both cases differ from previously reported cases of the Klippel-Trénaunay syndrome in lacking any prominent facial nevus flammeus. In the first case there was also malformation of the crown of the first permanent molar on the affected side that has not been described previously.

[Erbium:YAG laser phacoemulsification. Comparison of 2 different application systems]. / Erbium:YAG-Laser-Phakoemulsifikation. Vergleich von 2 verschiedenen Applikationssystemen.

BACKGROUND: The erbium:YAG laser a suitable energy source for photoablation of several tissues with only minimal thermal side effects. The application system is an important factor in increasing its efficiency. MATERIALS AND METHODS: We used an Er:YAG laser designed for clinical application. The energy was guided via a special coated zirconium fluoride fiber to handpieces of various designs. Twenty lenses of patient eyes were treated using two application systems with 0 degree and 30 degrees tips. RESULTS: Despite similar cataract density an average laser phacoemulsification took significantly less energy and less time using the 0 degree tip. CONCLUSIONS: Use of the Er:YAG laser is superior to ultrasound phacoemulsification in minimizing thermal energy required for lens removal. Certain parameters of the application system construction, in this case the 0 degree tip, can provide additional efficiency. Further developments should pay attention to these findings.

Nursing-bottle syndrome caused by prolonged drinking from vessels with bill-shaped extensions.

Our investigating 186 infants between the ages of one and six with carious destruction of the maxillary primary incisors, it was learned which risk factors were responsible for the condition known as nursing bottle syndrome. One hundred and twenty-eight infants (68.8 percent) were given a nursing bottle, twelve (6.5 percent) a feeding cup or other bottles with bill- shaped extensions, and forty-one (22.0 percent) both a nursing bottle and vessels with bill-shaped extensions; in all cases the feeding was excessive and prolonged beyond the first year of life. An additional five infants (2.7 percent) were breast-fed excessively beyond the first year. The results confirm the risk of tooth destruction, typical of nursing bottle syndrome, by prolonged and frequent consumption of cariogenic beverages from vessels with bill-shaped extensions. It is important, therefore, that a warning regarding dental health hazards of such feeding methods be issued.

Clinical and serological aspects of patients with anti-Jo-1 antibodies--an evolving spectrum of disease manifestations.

The aim of this study was to compare ELISA, immunodiffusion and immunoblot for the detection of anti-Jo-1 antibodies, and to investigate the association of the results with clinical manifestations. In two medical centres for rheumatology and one for pulmonology, all patients with suspected connective tissue disease were screened over a 5-year period for anti-Jo-1 antibodies by ELISA. Positive sera were controlled in another laboratory by immunodiffusion. If immunodiffusion was negative, sera were controlled again by ELISA. ELISA-positive immunodiffusion-negative sera were tested by immunoblotting. The patients were characterised clinically, and their clinical signs and symptoms were compared with those of 257 patients with anti-Jo-1 antibodies published in 15 case series and 30 case reports. Twenty-five patients had a positive ELISA test. Fifteen sera were positive by ELISA and immunodiffusion (group 1). Three sera showed high titres in both ELISA tests with negative immunodiffusion and immunoblot (group 2). Seven sera showed low titres in both ELISA tests. The results were negative in the other tests (group 3). Patients in groups 1 and 2 could be classified as Jo-1 syndrome patients. Of these 18 patients, 15 had arthritis, 14 had myositis and 14 had interstitial lung disease. Only four patients had myositis at disease onset. We describe four unusual patients with Jo-1 syndrome in detail: 1. Long history of seronegative rheumatoid arthritis; 2. Sjögren's syndrome with Ro- and La-antibodies; 3. Scleroderma and bronchial carcinoma with centromere antibodies; 4. Corticoid-sensitive psychosis. Patients with suspected connective tissue disease may be screened for anti-Jo-1 antibodies by ELISA. It detects some patients that are missed by immunodiffusion. Especially lower ELISA titres should be controlled by another method because of the low specificity of the test. The clinical picture is variable. Most patients have features other than myositis at disease onset.

The treatment of mandibular cysts associated with osteogenesis imperfecta.

A fifteen-year-old boy with osteogenesis imperfecta (OI) and dentinogenesis imperfecta also had a big cyst in the mandible and needed surgical therapy. Six months postoperatively we saw a complete regeneration of the bone-structures. We came to the conclusion that cysts which appear independently from the disease of OI can heal after surgical intervention.

Bilateral ablation of auditory cortex in Mongolian gerbil affects discrimination of frequency modulated tones but not of pure tones.

This study examines the role of auditory cortex in the Mongolian gerbil in differential conditioning to pure tones and to linearly frequency-modulated (FM) tones by analyzing the effects of bilateral auditory cortex ablation. Learning behavior and performance were studied in a GO/NO-GO task aiming at avoidance of a mild foot shock by crossing a hurdle in a two-way shuttle box. Hurdle crossing as the conditioned response to the reinforced stimulus (CR+), as false alarm in response to the unreinforced stimulus (CR-), intertrial activity, and reaction times were monitored. The analysis revealed no effects of lesion on pure tone discrimination but impairment of FM tone discrimination. In the latter case lesion effects were dependent on timing of lesion relative to FM tone discrimination training. Lesions before training in naive animals led to a reduced CR+ rate and had no effect on CR- rate. Lesions in pretrained animals led to an increased CR- rate without effects on the CR+ rate. The results suggest that auditory cortex plays a more critical role in discrimination of FM tones than in discrimination of pure tones. The different lesion effects on FM tone discrimination before and after training are compatible with both the hypothesis of a purely sensory deficit in FM tone processing and the hypothesis of a differential involvement of auditory cortex in acquisition and retention, respectively.

Effect of dental treatment and/or local application of amphotericin B to carious teeth on oral colonization by Candida.

Microbiological analyses of saliva and swabs were obtained from carious lesions of 54 children and adolescents with carious teeth, and of 49 boys and girls with healthy teeth. Candida species were isolated from the saliva of 36 (66.7%) subjects with active caries, but from the saliva of only one (2%) of the 49 caries-free subjects. Candida was detected in material removed from the carious lesion in 44 (81.5%) of the children with caries. Thirty patients with carious teeth and colonized by Candida were randomly divided into three groups of 10 individuals each, and either treated by complete dental restoration, by local application of amphotericin B or by a combination of dental treatment plus amphotericin B. The final microbiological control showed that thorough dental treatment alone eliminated fungi from the oral cavity in 90% of cases, whereas the local application of amphotericin B alone had a minimal effect on the candidal colonization of carious lesions. When, in addition to dental treatment, amphotericin B was applied, fungi were completely eliminated from the oral cavity of all subjects.

Micronized progesterone: a new option for women's health care.

Although progestational agents have been widely used for gynecologic conditions, treatment options have usually been limited to synthetic agents with adverse effects and sparse patient acceptance. Recent Food and Drug Administration approval of oral micronized progesterone (MP) has introduced therapy with a safe, effective, well-tolerated drug. This article reviews therapeutic indications for MP as illustrated in five case studies. Issues of patient compliance, individualized treatment plans, and patient partnership to obtain the most beneficial outcomes are discussed.

A specific role for group I mGluRs in hippocampal LTP and hippocampus-dependent spatial learning.

Metabotropic glutamate receptors (mGluRs) have been implicated in long-term potentiation and in learning and memory formation. In this study, we tested the effects of group I mGluR inhibition on synaptic plasticity and learning of rats at different levels of organization (1) in the hippocampal slice preparation; (2) in freely moving animals implanted with chronic hippocampal electrodes; and (3) in different spatial learning paradigms. To allow a direct comparison of the effects obtained the same doses were used in all paradigms. Bath-application of the selective group I mGluR antagonist (S)4-carboxyphenylglycine (4-CPG) impaired a decremental long-term potentiation (LTP) induced by a weak tetanization paradigm, but failed to affect a robust LTP generated by strong tetanization. In contrast, 4-CPG impaired a robust LTP in freely moving animals if applied 30 min before tetanization. The same dose of 4-CPG only impeded spatial learning mildly in the eight-arm radial maze and had no effect on a simple configuration of the Y-maze spatial alternation task. In the more difficult configuration of this task, however, 4-CPG caused complete amnesia. The lack of state-dependent 4-CPG actions and the absence of any 4-CPG effects in the open-field test classify the obtained retention deficit as a selective impairment of memory storage. Our results indicate a specific role of group I mGluRs in certain types of synaptic plasticity and of spatial learning.