Sleep disorders in women: clinical evidence and treatment strategies.

Sleep disorders are more prevalent in women than in men. Sex hormones modulate sleep-wake behaviors and mood and may contribute to heightened risk across the life cycle of women. Sleep disorders may have a unique expression in women, emerging throughout their reproductive life cycle. These conditions require careful treatment strategy to manage medical, hormonal, and behavioral contributing factors to poor sleep efficiency and impaired quality of life. This review focuses on clinical evidence for sleep disorders in women and discusses existing evidence of risk factors and treatment options for insomnia and sleep-disordered breathing in women.     

Selecting antibodies to detect HER2 overexpression by immunohistochemistry in invasive mammary carcinomas.

There is an increasing clinical demand for HER2 analysis in breast cancer, especially since the release of trastuzumab. The authors assessed the ability of immunohistochemistry to detect HER2 overexpression in invasive mammary carcinomas (IMC) using five antibodies. Paraffin-embedded samples of 86 IMCs (T2N0) were used to compare the immunohistochemical overexpression of HER2 using two polyclonal antibodies (HercepTest [DAKO] and A0485 [DAKO]) and three monoclonal antibodies (CB11 from two different laboratories, Biogenex and Novocastra, and 4D5 [Genentech]). All immunostainings were scored according to the FDA-approved HercepTest recommendations. The HercepTest-positive cases were compared with gene amplification by FISH (Oncor Inform, Ventana). The HercepTest was positive in 31 of the 86 cases (36.1%). The DAKO antibody A0485 was positive in 25 of the 66 (37.8%). Monoclonal antibody 4D5 was positive in only 15 of the 86 cases (17.4%). There was almost total agreement in results between the two CB11 antibodies: 25 of the 86 positive cases (29.1%). All cases positive for CB11 or 4D5 were HercepTest positive. Most of the HercepTest 2+ cases were negative when using either monoclonal antibody. FISH was positive in 19 of the 20 HercepTest 3+ cases and negative in 5 HercepTest 2+ cases. Three CB11-2+ cases showed no amplification by FISH. In three FISH-positive cases the immunohistochemistry showed no overexpression by all antibodies used. These findings suggest that immunohistochemistry may be used reliably as a primary methodology for evaluating HER2; however, the use of polyclonal antibodies may not be adequate to assess HER2 overexpression. CB11, regardless of the manufacturer (Biogenex or Novocastra), showed better concordance with FISH (kappa=0.83) than did the polyclonal antibodies.     

Neoplasia sincrónica de endometrio y ovario

We report the case of a patient with synchronous neoplasms of the endometrium and ovary, which developed at a relatively young age (45 years). Clinical presentation consisted of hypermenorrhea. An ovarian tumor was subsequently detected through ultrasound and computed tomography. Pathological examination revealed endometrioid histology at both sites and, as in most synchronous tumors occurring in these locations, both the grade and the stage of the tumors were low. All these factors indicate a good prognosis.     

Low molecular weight advanced glycation end products predict mortality in asymptomatic patients receiving chronic haemodialysis.

BACKGROUND: Advanced glycation end products (AGEs) have biological properties that may contribute to the premature cardiovascular mortality of haemodialysis patients. This study examines the hypothesis that low molecular weight forms of fluorescent AGEs (LMW fluorescence) predict mortality in haemodialysis patients. METHODS: The LMW fluorescence was measured in 85 patients treated with chronic haemodialysis and prospectively followed for 4 years. The primary outcome of all-cause mortality was assessed using Cox proportional hazards regression model. RESULTS: At the end of the follow-up period 37 (44%) patients died. The median LMW fluorescence level was 24.2 arbitrary units (range: 10.6-148.1 AU) and the receiver operator characteristic (ROC) curve cut-off for mortality was 37.0 AU. The LMW fluorescence predicted death both as a binary variable at the ROC cut-off, and as a continuous log-transformed variable when adjusted for age, albumin and C-reactive protein (CRP). Adjusted for age, albumin and CRP, the hazard ratio for mortality was 3.05 (1.41-6.60, P = 0.005) for LMW fluorescence as a binary variable and 2.71 per log unit (1.37-5.38, P = 0.004) as a continuous log-transformed variable. CONCLUSION: The low molecular weight forms of AGEs predict mortality in patients receiving chronic haemodialysis, and may be important in the mechanisms leading to atherosclerosis and inflammation in such patients.     

Magnetic resonance imaging of the craniocervical junction

Magnetic resonance imaging has become the study of choice for the majority of abnormalities of the craniocervical junction as well as for demonstration of primary pathology of the spinal cord, and brain stem. Although the applications of MR are currently limited by its high cost, relatively long scan time, and low sensitivity to calcification, new pulse sequences, faster scan strategies, and lower cost MR scanner are changing this situation. MR contrast agents and the use of 3-D imaging techniques combined with gradient echoes promise to play a role in MR of the craniocervical junction in the near future.     

Effects of cardiac and renal disease on clinical pharmacokinetics]

In this oral presentation, the author emphasized the need for individualization of drug treatment, reviewing the most known factors of variability in drug response. The importance of studies of clinical pharmacokinetics was focused. The main parameters for a judgement on the efficacy and virtual tolerability of a medicine, on the basis of its sequential concentrations in the blood after administration, were briefly outlined. The influence of congestive heart failure on the volume of distribution, systemic clearance, elimination half-life and bioavailability, was discussed. The changes that renal failure makes in drug elimination were equally presented, having been pointed the modification of protein binding, volume of distribution, and hepatic elimination. A selection of eight clinical cases was summarily presented, to illustrate the important contribute that can be afforded to practice by pharmacokinetics. The dosing of aminoglycosides and of other drugs with narrow therapeutic ranges was evaluated through some of the examples. A case of complex interferences of heart failure, renal failure and therapeutic hemoperfusion on the kinetics of an antibiotic drug was included. Two cases of intoxications (phenytoin and theophylline), whose management has been greatly improved by repeated drug dosing in blood, were discussed, too. A special call of attention was made to the need the currently practicing physician has of being aware of kinetic characteristics of the drugs he prescribes, and of how can disease modify the body fate of those medicines, and their therapeutic and nontherapeutic effects.     

Dentoskeletal treatment changes in Class II subdivision malocclusions in submentovertex and posteroanterior radiographs.

The objective of this study was to evaluate the dentoskeletal changes consequent to orthodontic treatment in subjects with Class II subdivision malocclusions, treated with asymmetric extractions, compared with a normal-occlusion control group. The sample consisted of 3 groups, with 30 subjects in each: normal-occlusion subjects (group 1), untreated Class II subdivision subjects (group 2), and Class II subdivision patients treated with asymmetric extractions (group 3). All subjects had a full complement of permanent teeth at the beginning of treatment. The average ages of the subjects were 22.42, 15.76, and 18.57 years, respectively, in groups 1, 2, and 3. Measurements of relative differences in the spatial position of dental and skeletal bilateral landmarks were obtained from the submentovertex and posteroanterior cephalometric (PA) radiographs. The t test for independent samples was used to compare group 1 with groups 2 and 3 at different times. Results from the submentovertex radiograph showed that asymmetric extractions in Class II subdivision malocclusions will maintain the differences in the anteroposterior positions of right and left, maxillary and mandibular first molars, as would be expected with the treatment protocols used. There were no significant skeletal changes that could be attributed to the treatment approaches investigated or transverse collateral effects with the asymmetric mechanics used. It was also demonstrated that treatment of Class II subdivision malocclusions with asymmetric extractions produced corrections of maxillary and mandibular dental midline deviations with the midsagittal plane, without canting the occlusal plane or any other investigated horizontal plane, as seen in the PA radiograph. Treatment of Class II subdivision malocclusions with asymmetric extractions constitutes a beneficial approach to this problem.     

Leakage of 4 resin-based root-canal sealers used with a single-cone technique.

OBJECTIVE: The aim of this study was to measure leakage of 4 resin-based sealers. STUDY DESIGN: Four groups of premolars (n = 60) were prepared using GT Rotary files and the crown-down technique and filled by the single-cone technique with AH26, AHPlus, EndoREZ, and an experimental MBP as sealer. Leakage was measured using the fluid filtration method after 15, 30, and 60 days and determined as microL/min(-1) x 10 psi. RESULTS: Statistical analysis by ANOVA and Tukey HSD test indicated that root fillings with AH Plus and the MBP showed lower leakage values after 15 days (P < .05). At 30 days, AH26 presented higher leakage values when compared to other sealers (P < .05). At 60 days, MBP and AH Plus presented the lower leakage values, differing significantly from EndoREZ (P < .05). CONCLUSION: It was observed that AH Plus and the experimental MBP showed lower leakage after 60 days than AH 26 and EndoREZ.     

Type 2 diabetes: assessment of endothelial lesion and fibrinolytic system markers.

This study aimed to investigate whether endothelial cells are damaged and to evaluate fibrinolytic system function in patients with type 2 diabetes. For this proposal, plasma levels of von Willebrand factor (an endothelial marker of injury), homocysteine (an inductor of endothelial injury), D-dimer (a marker of coagulation cascade activation) and plasminogen activator inhibitor-1 (a fibrinolysis marker) were measured in individuals with both type 2 diabetes and high blood pressure, with type 2 diabetes, with high blood pressure and in healthy control individuals. No significant differences among groups were observed for von Willebrand factor and homocysteine plasma levels. The type 2 diabetes and high blood pressure group presented a significant difference to the other groups for D-dimer and also presented high values for plasminogen activator inhibitor-1. The high blood pressure group and type 2 diabetes group presented separately higher values of plasminogen activator inhibitor-1 compared with the control group. High levels of D-dimer and plasminogen activator inhibitor-1 in patients with type 2 diabetes and high blood pressure with normoalbuminuria therefore indicate a state of hypercoagulability and hypofibrinolysis, despite no evident microvascular injury supported by normal levels of von Willebrand factor and homocysteine.     

Partial replication of a DRD4 association in ADHD individuals using a statistically derived quantitative trait for ADHD in a family-based association test.

BACKGROUND: Previous research found an association between single nucleotide polymorphisms (SNPs) in the promoter region of DRD4 and statistically derived phenotypes generated from attention-deficit/hyperactivity disorder (ADHD) symptoms. We sought to replicate this finding by using the same methodology in an independent sample of ADHD individuals. METHODS: Four SNPs were genotyped in and around DRD4 in 2631 individuals in 642 families. We developed a quantitative phenotype at each SNP by weighting nine inattentive and nine hyperactive-impulsive symptoms. The weights were selected to maximize the heritability at each SNP. Once a quantitative phenotype was generated at each SNP, the screening procedure implemented in PBAT was used to select and test the five SNPs/genetic model combinations with the greatest power to detect an association for DRD4. RESULTS: One of the four SNPs was associated with the quantitative phenotypes generated from the ADHD symptoms (corrected p-values = .02). A rank ordering of the correlation between each of the ADHD symptoms and the quantitative phenotype suggested that hyperactive-impulsive symptoms were more strongly correlated with the phenotype; however, including inattentive symptoms was necessary to achieve a significant result. CONCLUSIONS: This study partially replicated a previous finding by identifying an association between rs7124601 and a quantitative trait generated from ADHD symptoms. The rs7124601 is in linkage disequilibrium (LD) with the SNPs identified previously. In contrast to the previous study, this finding suggests that both hyperactive-impulsive and inattentive symptoms are important in the association.