A premaxilla with a supernumerary tooth indicating a developmental region with a variety of dental abnormalities: a report of nine cases

The aim of this study was to elucidate whether a premaxilla with a supernumerary tooth has additional dental abnormalities. The study does not include premaxillas with a mesiodens, only premaxillas with parasagittally located supernumerary teeth. Radiographs from eight children, followed from 1 year and 5 months to 11 years and 5 months in the municipal dental health service in Denmark, were analyzed. One patient was seen only once. Dental abnormalities recorded included: invaginations on permanent incisors, resorption of roots of incisors, curved roots of incisors, delayed eruption, and delayed formation of roots. The study shows that there are dental abnormalities within the premaxillary region where the supernumerary tooth is located. This indicates that, apart from the supernumerary tooth, a more widespread deviation from normal conditions including tooth malformation, arrested eruption, and root resorption occur within the premaxillary region. The most important outcome of this study is that in the region with a supernumerary tooth the adjacent incisor shows delayed eruption after surgical removal of the supernumerary tooth. The deviations in root morphology, including root resorption, are not limited to patients who have had orthodontic treatment, but patients who did not receive orthodontic treatment also revealed deviations in root morphology. Therefore the treatment outcome can be different from the expected outcome.     

Awake craniotomies without any sedation: the awake-awake-awake technique

Background

Temporary anaesthesia or analgosedation used for awake craniotomies carry substantial risks like hemodynamic instabilities, airway obstruction, hypoventilation, nausea and vomiting, agitation, and interference with test performances. We tested the actual need for sedatives and opioids in 50 patients undergoing awake craniotomy for brain tumour resection in eloquent or motoric brain areas when cranial nerve blocks, permanent presence of a contact person, and therapeutic communication are provided.

Methods

Therapeutic communication was based on the assumption that patients in such an extreme medical situation enter a natural trance-like state with elevated suggestibility. The anaesthesiologist acted as a continuous guide, using a strong rapport, nonverbal communication, hypnotic suggestions, such as dissociation to a “safe place”, and the reframing of disturbing noises, while simultaneously avoiding negative suggestions. Analgesics or sedatives were at hand according to the principle “as much as necessary, but not more than needed”.

Results

No sedation was necessary for any of the patients besides for the treatment of seizures. Only two-thirds of the patients requested remifentanil, with a mean dosage of 96 μg before the end of tumour resection and a total of 156 μg. Hemodynamic reactions indicative of stress were mainly seen during nerve blockades and neurological testing. Postoperative vigilance tests showed equal or higher scores than preoperative tests.

Conclusions

The main challenges for patients undergoing awake craniotomies include anxiety and fears, terrifying noises and surroundings, immobility, loss of control, and the feeling of helplessness and being left alone. In such situations, psychological support might be more helpful than the pharmacological approach. With adequate therapeutic communication, patients do not require any sedation and no or only low-dose opioid treatment during awake craniotomies, leaving patients fully awake and competent during the entire surgical procedure without stress. This approach can be termed “awake-awake-awake-technique”.     

Chronic Treatment With a Melanocortin-4 Receptor Agonist Causes Weight Loss,Reduces Insulin Resistance,and Improves Cardiovascular Function in Diet-Induced Obese Rhesus Macaques

The melanocortin-4 receptor (MC4R) is well recognized as an important mediator of body weight homeostasis. Activation of MC4R causes dramatic weight loss in rodent models, and mutations in human are associated with obesity. This makes MC4R a logical target for pharmacological therapy for the treatment of obesity. However, previous studies in rodents and humans have observed a broad array of side effects caused by acute treatment with MC4R agonists, including increased heart rate and blood pressure. We demonstrate that treatment with a highly-selective novel MC4R agonist (BIM-22493 or RM-493) resulted in transient decreases in food intake (35%), with persistent weight loss over 8 weeks of treatment (13.5%) in a diet-induced obese nonhuman primate model. Consistent with weight loss, these animals significantly decreased adiposity and improved glucose tolerance. Importantly, we observed no increases in blood pressure or heart rate with BIM-22493 treatment. In contrast, treatment with LY2112688, an MC4R agonist previously shown to increase blood pressure and heart rate in humans, caused increases in blood pressure and heart rate, while modestly decreasing food intake. These studies demonstrate that distinct melanocortin peptide drugs can have widely different efficacies and side effects.Maintenance of body weight and energy homeostasis requires balance between energy intake and expenditure and is achieved via the interaction between central and peripheral signals. The central melanocortin system is one of the key neural circuits involved in mediating the integration of information from both sites. Proopiomelanocortin is a prohormone that is processed into multiple bioactive peptides, including α-melanocyte–stimulating hormone (MSH), β-MSH, γ-MSH, and the endogenous opioid β-endorphin (1). α-MSH, or its analogs, are potent inhibitors of food intake and increase energy expenditure to promote weight loss in rodent and rhesus macaque models (2–5). Central melanocortins are involved in many physiological functions, including stress responses; however, their actions on the regulation of food intake and energy expenditure have been a focus.Melanocortin-4 receptor (MC4R) is the main melanocortin receptor involved in the regulation of food intake and energy expenditure, primarily through modulation of sympathetic outflow (6–8). MC4R has a broad distribution, including expression in several peripheral tissues, such as muscle, kidney, and lung (9). The importance of MC4R in the maintenance of body weight homeostasis is highlighted by genetic studies in humans and mice. MC4R^−/− mice are hyperphagic, have increased adipose and lean mass, and develop insulin resistance (10). In humans, mutations in the proopiomelanocortin gene (11) and the MC4R gene have a similar phenotype (12–14).Although the effects of MC4R agonists on energy/glucose homeostasis (15,16) make it an attractive target for a therapeutic agent, the potential side effects of increasing heart rate and blood pressure have been a major limitation (17). Indeed, recent studies reported by Greenfield et al. (18) showed that acute peripheral administration with a centrally acting MC4R selective agonist increased blood pressure and heart rate in moderately obese humans. There is an obvious concern in treating obese individuals with a high risk of hypertension and cardiovascular disease with a weight loss therapy that is exacerbating these same risks. In the current study, we use a diet-induced obesity (DIO) nonhuman primate model (NHP) to determine if long-term treatment with the MC4R-specific agonist BIM-22493 can reduce food intake and adiposity without adversely affecting cardiovascular function.     

Fibrillin-1 genotype and risk of prevalent hypertension: A study in two independent populations

Abstract Objective. Mutations in the fibrillin-1 gene are the cause of Marfan syndrome. We wanted to investigate the relationship between a mutation in this gene and risk of prevalent hypertension. Methods. In a cross-sectional study, the effect of a G-A substitution in intron 27 in the fibrillin-1 gene (rs11856553) on risk of prevalent hypertension was studied in two large population-based studies: the Health 2006 study, consisting of 3193 women and men, age 18-69 years, and the MONICA10 study, consisting of 2408 women and men, age 41-72 years. In 1646 MONICA10 participants, blood pressure (BP) was also measured by 24-h ambulatory recordings. Results. Among the 3193 Health 2006 participants 23 had the G-A variant, and among the 2408 MONICA10 participants 18 had the G-A variant. In Health 2006, the odds ratio estimate (95% confidence intervals) for the G-A variant for risk of hypertension, defined as systolic (S) BP ≥?140 mmHg or diastolic (D) BP ≥?90 mmHg or on antihypertensive medicine, was 2.67 (1.14-6.18), p =?0.022. The corresponding figure for moderate to severe hypertension, defined as SBP ≥?160 mmHg or DBP ≥?100 mmHg, was 9.68 (4.24-22.12), p 相似文献   

Methylglyoxal alters glucose metabolism and increases AGEs content in C6 glioma cells

Methylglyoxal is a dicarbonyl compound that is physiologically produced by enzymatic and non-enzymatic reactions. It can lead to cytotoxicity, which is mainly related to Advanced Glycation End Products (AGEs) formation. Methylglyoxal and AGEs are involved in the pathogenesis of Neurodegenerative Diseases (ND) and, in these situations, can cause the impairment of energetic metabolism. Astroglial cells play critical roles in brain metabolism and the appropriate functioning of astrocytes is essential for the survival and function of neurons. However, there are only a few studies evaluating the effect of methylglyoxal on astroglial cells. The aim of this study was to evaluate the effect of methylglyoxal exposure, over short (1 and 3?h) and long term (24?h) periods, on glucose, glycine and lactate metabolism in C6 glioma cells, as well as investigate the glyoxalase system and AGEs formation. Glucose uptake and glucose oxidation to CO₂ increased in 1?h and the conversion of glucose to lipids increased at 3?h. In addition, glycine oxidation to CO₂ and conversion of glycine to lipids increased at 1?h, whereas the incorporation of glycine in proteins decreased at 1 and 3?h. Methylglyoxal decreased glyoxalase I and II activities and increased AGEs content within 24?h. Lactate oxidation and lactate levels were not modified by methylglyoxal exposure. These data provide evidence that methylglyoxal may impair glucose metabolism and can affect glyoxalase activity. In periods of increased methylglyoxal exposure, such alterations could be exacerbated, leading to further increases in intracellular methylglyoxal and AGEs, and therefore triggering and/or worsening ND.     

Genetic variation in the natriuretic Peptide system, circulating natriuretic Peptide levels, and blood pressure: an ambulatory blood pressure study

BackgroundIn a large collaborative study (n > 50,000), common variants in the natriuretic peptide (NP) genes were found to be associated with circulating NP levels and also with blood pressure (BP) levels based on office BP measurements (OBPMs). It is unknown if determining an individual's BP by 24-h ambulatory BP measurements (ABPMs) will influence the effect of NP gene variations on BP levels.MethodsWe used rs632793 at the NPPB (NP precursor B) locus to investigate the relationship between genetically determined serum N-terminal pro-brain NP (NT-proBNP) concentrations and BP levels determined by both 24-h ABPMs and OBPMs in a population consisting of 1,397 generally healthy individuals taking no BP-lowering drugs.Resultsrs632793 was significantly correlated with serum Nt-proBNP levels (r = 0.10, P = 0.0003), and participants with the A:A genotype had lower serum Nt-proBNP levels than participants with the G:G genotype (geometric mean (95% confidence interval (CI)): 34.8 (31.5-38.4) pg/ml vs. 48.1 (41.9-55.3) pg/ml, P = 0.0002), but higher 24-h ambulatory BP levels (mean difference (95% CI): 2.0 (0.1-4.1) mm Hg, P = 0.043, for systolic BP and 1.7 (0.4-3.1) mm Hg, P = 0.011, for diastolic BP). Office BP decreased across the genotypes from A:A to G:G, but the differences did not reach statistical significance (P ≥ 0.12).ConclusionsThis study suggests that 24-h ABPMs is a better method than OBPMs to detect significant differences in BP levels related to genetic variance and provides further evidence that the NP system plays an important role in BP regulation.American Journal of Hypertension 2012; doi:10.1038/ajh.2012.96.     

Cardiac Resynchronization Therapy: Do Women Benefit More Than Men?

Gender and Resynchronization Therapy. Introduction: Women are underrepresented in cardiac resynchronization therapy (CRT) trials. Whether there is a gender difference in the benefit derived from CRT has not been well studied. Methods: This study included 728 consecutive CRT recipients at our institution who met guidelines for placement of a CRT device. Clinical characteristics and echocardiographic parameters were collected at baseline and after CRT; Kaplan–Meier survival analysis was performed using a national death and location database. The effects and outcome of CRT were compared between women and men. Results: Of 728 patients, 166 were female (22.8%). Female patients were younger than male patients (66.0 ± 11.9 years vs 69.4 ± 10.9 years; P < 0.001) and more often had nonischemic cardiomyopathy (68% vs 36%; P < 0.001). Both female and male patients had significantly improved clinical and echocardiographic parameters after CRT. The magnitude of improvement was similar in women and men, except that improvement in New York Heart Association (NYHA) class was greater in women than in men (–0.79 ± 0.78 vs –0.56 ± 0.85; P = 0.009). Although women were at lower risk of death than men after CRT (hazard ratio, 0.51; 95% confidence interval, 0.35–0.75; P < 0.001, unadjusted), multivariate analysis indicated gender was not, but age at CRT placement, cardiomyopathy cause, NYHA class, and lead location were independent predictors of survival. Conclusion: Female CRT recipients seem to achieve greater survival benefit than male recipients. However, this benefit is majorly driven by nonischemic cardiomyopathy and other clinical factors. (J Cardiovasc Electrophysiol, Vol. 23, pp. 172‐178, February 2012)