Influence of Estrogen Deficiency on Bone Around Osseointegrated Dental Implants: An Experimental Study in the Rat Jaw Model

Purpose: The aim of this study was to evaluate the influence of estrogen deficiency on bone around osseointegrated dental implants in a rat jaw model. Materials and Methods: This study used 16 female rats that had the first molars bilaterally extracted and were allowed to heal for 30 days before implant placement. Sixty days after implant placement, the animals were randomly subjected to sham surgery or ovariectomy (OVX). The animals were euthanized 90 days after OVX. Bone-to-implant contact, bone area fraction occupancy between implant threads, mineral density, turnover markers, and cells positive for tartrate-resistant acid phosphatase were assessed for the 2 groups. Results: The results showed that OVX group presented a decrease of systemic bone density, alterations in bone turnover markers, and an increase of cells positive for tartrate-resistant acid phosphatase compared with the sham-surgery group. However, no difference relative to bone-to-implant contact and bone area fraction occupancy was observed between groups. Conclusions: The findings of this study demonstrate that estrogen deficiency may not be considered a risk factor for osseointegrated implant failure in jaw bone. (C) 2011 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 69:1911-1918, 2011

Discrete and continuous models for dry masonry columns

The dynamic response of dry masonry columns can be approximated with finite-difference equations. Continuum models follow by replacing the difference quotients of the discrete model by corresponding differential expressions. The mathematically simplest of these models is a one-dimensional Cosserat theory. Within the presented homogenization context, the Cosserat theory is obtained by making ad hoc assumptions regarding the relative importance of certain terms in the differential expansions. The quality of approximation of the various theories is tested by comparison of the dispersion relations for bending waves with the dispersion relation of the discrete theory. All theories coincide with differences of less than 1% for wave-length-block-height (L/h) ratios bigger than 2 pi. The theory based on systematic differential approximation remains accurate up to L/h = 3 and then diverges rapidly. The Cosserat model becomes increasingly inaccurate for L/h < 2 pi. However, in contrast to the systematic approximation, the wave speed remains finite. In conclusion, considering its relative simplicity, the Cosserat model appears to be the natural starting point for the development of continuum models for blocky structures.

Encephalitogenicity of murine, but not bovine, DM20 in SJL mice is due to a single amino acid difference in the immunodominant encephalitogenic epitope

Myelin proteolipid protein (PLP) contains 2 immunodominant encephalitogenic epitopes in SJL mice, namely PLP residues 139-151 and 178-191. DM20, a minor isoform of PLP, lacks residues 116-150 and consequently contains only the single major encephalitogenic epitope 178-191. However, it has been found previously that bovine DM20 is not encephalitogenic in SJL mice. Since residue 188 within peptide 178-191 is phenylalanine (F) in murine DM20 and alanine (A) in bovine DM20, we tested the effect of this difference on the immune responses and induction of EAE. SJL mice were immunized with either highly purified murine or bovine DM20. Residues 178-191 were found to be immunodominant for each, but only murine and not bovine DM20 was encephalitogenic. A synthetic peptide corresponding to the murine 178-191 sequence (F188) was also encephalitogenic, whereas the peptide corresponding to the bovine sequence (A188) was not. Both F188 and A188 bind with high affinity to I-A(s) and both are recognized by the SJL T cell repertoire. A188-specific T cell lines reacted to both A188 and F188, but F188-specific T cell lines were not stimulated by A188. F188-specific T cell lines produced mRNA for the Th1 cytokines IL2 and IFN gamma and, in passive transfer experiments, were encephalitogenic upon stimulation with F188, but not A188. In contrast, A188-specific T cell lines produced mRNA for IL4, IL5 and IL10, in addition to IL2 and IFN gamma, and were not encephalitogenic after stimulation with either F188 or A188. Cotransfer of A188-specific T cell lines with F188-specific T cell lines resulted in protection from EAE. Thus, A188 induces a functionally different phenotype of T cells from that induced by F188. Taken together these data suggest that the failure of bovine DM20 to induce EAE may be attributable to induction of protective rather than pathogenic T cells by the immunodominant epitope.

The impact of diabetes on survival among patients with first myocardial infarction

OBJECTIVE - The purpose of this paper is to estimate the impact of diabetes on survival among patients with first acute myocardial infarction, using data from the World Health Organization (WHO) Monitoring Trends and Determinants of Cardiovascular Disease (MONICA) Project in Newcastle, New South Wales, Australia. RESEARCH DESIGN AND METHODS - The WHO MONICA Project is a community-based surveillance system that monitors coronary heart disease morbidity and mortality. All patients with suspected coronary events were observed for 28 days after the onset of symptoms. RESULTS - Of 5,322 patients with acute myocardial infarction and no previous history of ischemic heart disease (3,643 men and 1,679 women), 333 men (9%) and 224 women (13%) had a history of diabetes. The age-adjusted 28-day case fatality for women with diabetes (25%) was significantly higher than for women without diabetes (16%); relative risk 1.56 (95% CI: 1.19-2.04). The difference for men was also significant (25% with diabetes and 20% without diabetes); relative risk 1.25 (95% CI: 1.02-1.53). Age-specific case fatality increased significantly with age in both men and women without diabetes, but systematic age effects were not so apparent in patients with diabetes. Case fatality significantly decreased over the study period in patients without diabetes, but not among the diabetic patients. CONCLUSIONS - The increased risk of death in the diabetic patients remained after accounting for their poorer risk factor profiles; even if they reached the hospital alive, diabetic patients were also less likely to survive than nondiabetic patients. The relative impact of diabetes on survival is greater in women than in men.

Smoking and relative body weight: An international perspective from the WHO MONICA project

Study objective-To investigate the magnitude and consistency of the associations between smoking and body mass index (BMI) in different populations. Design-A cross sectional study. Setting and participants-About 69000 men and women aged 35-64 years from 42 populations participating in the first WHO MONICA survey in the early and mid 1980s. Main restults-Compared to never smokers, regular smokers had significantly (p < 0.05) lower median BMI in 20 (men) and 30 (women) out of 42 populations (range -2.9 to 0.5kg/m(2)). There was no population in which smokers had a significantly higher BMI than never smokers. Among men, the association between leanness and smoking was less apparent in populations with relatively low proportions of regular smokers and high proportions of ex-smokers. Ex-smokers had significantly higher BMI than never smokers in 10 of the male populations but in women no consistent pattern was observed. Adjustment for socioeconomic status did not affect these results. Conclusions-Although in most populations the association between smoking and BMI is similar, the magnitude of this association may be affected by the proportions of smokers and ex-smokers in these populations.

Relative dispersion of intravascular transit times during isolated human limb perfusions for recurrent melanoma

Aims We have characterized the relative dispersion of vascular and extravascular markers in the limbs of three patients undergoing isolated limb perfusions with the cytotoxic melphalan for recurrent malignant melanoma both before and after melphalan dosing. Methods A bolus of injectate containing [Cr-51] labelled red blood cells, [C-14]-sucrose and [H-3]-water was injected into an iliac or femoral artery and outflow samples collected at 1 s intervals by a fraction collector. The radioactivity due to each isotype was analysed by either gamma [Cr-51] or beta [C-14 and H-3] counting. The moments of the outflow fraction-time profiles were estimated by a nonparametric (numerical integration) method and a parametric model (sum of two inverse Gaussian functions). Results The availability, mean transit time and normalised variance (CV2) obtained for labelled red blood cells, sucrose and water were similar before and after melphalan dosing and with the two methods of calculation but varied between the patients. Conclusions The vascular space is not well-stirred but characterized by a CV2 similar that reported previously for in situ rat hind limb and rat liver perfusions. A flow-limited blood-tissue exchange was observed for the permeating indicators. Administration of melphalan did not influence the distribution characteristics of the indicators.

Relationship between limb movement speed and associated contraction of the trunk muscles

Rapid shoulder movement is preceded by contraction of the abdominal muscles to prepare the body for the expected disturbance to postural equilibrium and spinal stability provoked by the reactive forces resulting from the movement. The magnitude of the reactive forces is proportional to the inertia of the limb. The aim of the study was to investigate if changes in the reaction time latency of the abdominal muscles was associated with variation in the magnitude of the reactive forces resulting from variation in limb speed. Fifteen participants performed shoulder flexion at three different speeds (fast, natural and slow). The onset of EMG of the abdominal muscles, erector spinae and anterior deltoid (AD) was recorded using a combination of fine-wire and surface electrodes. Mean and peak velocity was recorded for each limb movement speed for five participants. The onset of transversus abdominis (TrA) EMG preceded the onset of AD in only the fast movement condition. No significant difference in reaction time latency was recorded between the fast and natural speed conditions for all muscles. The reaction time of each of the abdominal muscles relative to AD was significantly delayed with the slow movement compared to the other two speeds. The results indicate that the reaction time latency of the trunk muscles is influenced by limb inertia only with limb movement below a threshold velocity.

Randomized Study of Surgical Prophylaxis in Immunocompromised Hosts

Although prophylaxis is current practice, there are no randomized controlled studies evaluating preoperative antimicrobial prophylaxis in dental procedures in patients immunocompromised by chemotherapy or organ transplants. To evaluate prophylaxis in dental-invasive procedures in patients with cancer or solid organ transplants, 414 patients were randomized to receive one oral 500-mg dose 2 hours before the procedure (1-dose group) or a 500-mg dose 2 hours before the procedure and an additional dose 8 hours later (2-dose group). Procedures were exodontia or periodontal scaling/root planing. Follow-up was 4 weeks. No deaths or surgical site infections occurred. Six patients (1.4%) presented with use of pain medication > 3 days or hospitalization during follow-up: 4 of 207 (2%) in the 1-dose group and 2 of 207 (1%) in the 2-dose group (relative risk, 2.02; 95% confidence interval, 0.37-11.15). In conclusion, no statistically significant difference occurred in outcome using 1 or 2 doses of prophylactic amoxicillin for invasive dental procedures in immunocompromised patients.

Sphenoid sinus symmetry and differences between sexes

Objectives: To evaluate the anatomic variations of neurovascular structures adjacent to the sphenoid sinus and their agreement between right and left sides as well as differences between sexes. Methods: Forty-five cadavers were dissected (24 men, and differences between sexes and agreement of anatomic variations of the sphenoid sinus between sides were analyzed. Results: The mean distance from the sphenoid sinus ostium to the anterior nasal spine was greater in males than in females by an average of 3.0 mm (p = 0.001) while the mean difference of distances between the right and left side was -1.1 +/- 3.1 mm. Female cadavers had a greater frequency of optic-carotid recess (p = 0.04) and dehiscence over the maxillary nerve (p = 0.02), as well as greater relative risk of optic nerve protrusion (p < 0.001), and dehiscence over the internal carotid artery (ICA) (p = 0.002). In male cadavers the intersinus septum was inserted on the course of the ICA 3.5 times more often than in female (p = 0.02). Agreement of anatomic variations between sides ranged from moderate to almost perfect depending on the structures evaluated. Conclusions: There are anatomic differences of the sphenoid sinus between sexes and between right and left sides, and these differences should be taken into consideration during surgery.

CLASSIFYING RADIUS FRACTURES WITH X-RAY AND TOMOGRAPHY IMAGING

Introduction: This study evaluated the interobserver reliability of plain radiograpy versus computed tomography (CT) for the Universal and AO classification systems for distal radius fractures. Patients and methods: Five observers classified 21 sets of distal radius fractures using plain radiographs and CT independently. Kappa statistics were used to establish a relative level of agreement between observers for both readings. Results: Interobserver agreement was rated as moderate for the Universal classification and poor for the AO classification. Reducing the AO system to 9 categories and to its three main types reliability was raised to a ""moderate"" level. No difference was found for interobserver reliability between the Universal classification using plain radiographs and the Universal classification using computed tomography. Interobserver reliability of the AO classification system using plain radiographs was significantly higher than the interobserver reliability of the AO classification system using only computed tomography. Conclusion: From these data, we conclude that classification of distal radius fractures using CT scanning without plain radiographs is not beneficial.

Relative Bioavailability of Two Oral Formulations of Risperidone 2 mg: A Single-Dose, Randomized-Sequence, Open-Label, Two-Period Crossover Comparison in Healthy Brazilian Volunteers

Background: Risperidone (RSP) is a benzisoxazole antipsychotic agent used to treat schizophrenia and other psychiatric illnesses in adults and children (including those with autism). After oral administration, RSP is completely absorbed from the gastrointestinal tract and undergoes hydroxylation to yield 9-hydroxyrisperidone (9-OH-RSP), an active metabolite that has a pharmacologic profile and potency similar to RSP. Objectives: The aims of this study were to compare the relative bioavailability of a pharmaceutical-equivalent (test) formulation with a reference formulation of oral RSP 2 mg, both available commercially on the Brazilian pharmaceutical market, and to generate data regarding the oral bioavailability of the tested drug in healthy Brazilian volunteers. Methods: This single-dose, randomized-sequence, open-label, 2-period crossover study was conducted in healthy Brazilian volunteers from August to December 2008. Subjects were randomly assigned to receive the test formulation followed by the reference formulation or vice versa, with a 30-day washout period between doses. Study drugs were administered after a 12-hour overnight fast. For pharmacokinetic analysis, blood samples were drawn at 0 (baseline), 0.25, 0.5, 1, 1.5, 3, 5, 8, 12, 24, 48, 72, 96, and 120 hours after administration. Plasma concentrations of RSP and 9-OH-RSP were determined using LC-MS/MS. The test and reference formulations were to be considered bioequivalent if the 90% CIs for the geometric mean test/reference ratios were within a predetermined range of 80% to 125%, in accordance with the policies of the Brazilian Sanitary Surveillance Agency and the US Food and Drug Administration. Tolerability was determined using clinical assessments, monitoring of vital signs, analysis of laboratory test results, and subject interviews regarding adverse events. Results: A total of 22 subjects were enrolled (11 men, 11 women; mean [SD] age, 32 [12] years [range, 18-58 years]; weight, 70.4 [11.9] kg [range, 50-103 kg]; height, 1.67 [0.08] m [range, 1.56-1.80 m]; and body mass index, 25 [4] kg/m(2) [range, 18-29 kg/m(2)]). For RSP, mean (SD) C(max) values were 12.6 (2.7) and 16.0 (2.3) ng/mL for the test and reference formulations, respectively. For 9-OH-RSP, mean C(max) values were 17.8 (1.3) and 21.0 (1.7) ng/mL for the test and reference formulations. The 90% CIs for the mean test/reference ratios for RSP C(max), AUC(0-120), and AUC(0-infinity) were 74% to 82%, 75% to 85%, and 76% to 85%, respectively, and 83% to 87%, 75% to 79%, and 75% to 78% for 9-OH-RSP. The related adverse events (headache, low back pain, drowsiness, standing hypotension, local postvenipuncture ecchymoses, insomnia, nausea, and vomiting) were transient and mild. Conclusions: This single-dose study found that the test and reference formulations of oral RSP 2 mg did not meet the Brazilian and US regulatory criteria for bioequivalence in these fasting, healthy volunteers. The study formulations appeared to be well tolerated. (Clin Ther 2010;32:2106-2115) (C) 2010 Elsevier HS Journals, Inc.

Lateral ventricle differences between first-episode schizophrenia and first-episode psychotic bipolar disorder: A population-based morphometric MRI study

Objectives. The extent to which psychotic disorders fall into distinct diagnostic categories or can be regarded as lying on a single continuum is controversial. We compared lateral ventricle volumes between a large sample of patients with first-episode schizophrenia or bipolar disorder and a healthy control group from the same neighbourhood. Methods. Population-based MRI study with 88 first-episode psychosis (FEP) patients, grouped into those with schizophrenia/schizophreniform disorder (N = 62), bipolar disorder (N = 26) and 94 controls. Results. Right and left lateral ventricular and right temporal horn volumes were larger in FEP subjects than controls. Within the FEP sample, post-hoc tests revealed larger left lateral ventricles and larger right and left temporal horns in schizophrenia subjects relative to controls, while there was no difference between patients with bipolar disorder and controls. None of the findings was attributable to effects of antipsychotics. Conclusions. This large-sample population-based MRI study showed that neuroanatomical abnormalities in subjects with schizophrenia relative to controls from the same neighbourhood are evident at the first episode of illness, but are not detectable in bipolar disorder patients. These data are consistent with a model of psychosis in which early brain insults of neurodevelopmental origin are more relevant to schizophrenia than to bipolar disorder.

(1)H magnetic resonance spectroscopy imaging of the hippocampus in patients with panic disorder

Recent theories of panic disorder propose an extensive involvement of limbic system structures, such as the hippocampus, in the pathophysiology of this condition. Despite this, no prior study has examined exclusively the hippocampal neurochemistry in this disorder. The current study used proton magnetic resonance spectroscopy imaging ((1)H-MRSI) to examine possible abnormalities in the hippocampus in panic disorder patients. Participants comprised 25 panic patients and 18 psychiatrically healthy controls. N-acetylaspartate (NAA, a putative marker of neuronal viability) and choline (Cho, involved in the synthesis and degradation of cell membranes) levels were quantified relative to creatine (Cr, which is thought to be relatively stable among individuals and in different metabolic condition) in both right and left hippocampi. Compared with controls, panic patients demonstrated significantly lower NAA/Cr in the left hippocampus. No other difference was detected. This result is consistent with previous neuroimaging findings of hippocampal alterations in panic and provides the first neurochemical evidence suggestive of involvement of this structure in the disorder. Moreover, lower left hippocampal NAA/Cr in panic disorder may possibly reflect neuronal loss and/or neuronal metabolic dysfunction, and could be related to a deficit in evaluating ambiguous cues. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

Acute increase in urinary 6-sulfatoximelatonin after clomipramine, as a predictive measure for emotional improvement

Nocturnal melatonin pineal output is triggered by sympathetic outflow. Antidepressants that block norepinephrine neuronal uptake should increase pineal function. This can be monitored by measuring 6-sulfatoximelatonin (aMT6s), the main melatonin metabolite, in the urine. In this study, we compared the excretion of aMT6s before (baseline), one, and 21 days after administration of clomipramine to healthy subjects (n = 32). At the end of treatment, subjects were divided into responders (n = 12) and non-responders (n = 20) according to the improvement in their emotional state in three out of four domains (interpersonal tolerance, efficiency, well-being and feeling different from the usual self). There was no difference in aMT6s before clomipramine between responders and non-responders in any of the time intervals analysed (06:00-12:00, 12:00-18:00, 18:00-24:00 and 24:00-06:00 hours). At day one, but not at day 21, the fraction of aMT6s excreted during the time interval 24:00-06:00, relative to the total amount excreted by each subject per day, was significantly higher (P = 0.0287) than baseline (0.57 +/- 0.04) in responders. No significant difference was observed in non-responders. The increase in pineal function induced by clomipramine was restricted to day one, indicating that long-lasting adaptation restores pineal function. In addition, the day one increase in aMT6s was significantly increased only in the responders group, raising the possibility that the blocking of neuronal uptake is predictive of emotional improvement.