Erectile dysfunction and cardiovascular disease

Cardiovascular disease (CVD) and erectile dysfunction (ED) are 2 closely intertwined disease processes. Over the past 2 decades, there have been many studies that have linked both conditions and established ED as a risk factor for CVD. In the United States and worldwide, a large population of adult men has ED and/or CVD. Worldwide, approximately 140 million men have ED, and the number is expected to double in the next 15 years. Because ED and CVD share many of the same risk factors, the relationship between CVD and ED is a very valid concern. Our goal is to examine the association and pathophysiological relationship between ED and CVD. We will also review common risk factors, current treatments, and management of the 2 conditions. Finally, we will discuss the risks of sexual activity in patients who have CVD.     

Prospective neoadjuvant analysis of PET imaging and mechanisms of resistance to Trastuzumab shows role of HIF1 and autophagy

Background:

Although Trastuzumab has improved survival of HER2+ breast cancer patients, resistance to the agent pre-exists or develops through the course of therapy. Here we show that a specific metabolism and autophagy-related cancer cell phenotype relates to resistance of HER2+ breast cancer to Trastuzumab and chemotherapy.

Methods:

Twenty-eight patients with locally advanced primary breast cancer were prospectively scheduled to received one cycle of Trastuzumab followed by a new biopsy on day 21, followed by taxol/Trastuzumab chemotherapy for four cycles before surgery. FDG PET/CT scan was used to monitor tumour response. Tissue samples were immunohistochemically analysed for metabolism and autophagy markers.

Results:

In pre-Trastuzumab biopsies, the LC3A+/HER2+ cell population was correlated with HIF1α expression (P=0.01), while GLUT1 and LC3B expression were correlated with Ki67 proliferation index (P=0.01 and P=0.01, respectively). FDG PET tumour dimensions before therapy were correlated with LC3B expression (P=0.005). Administration of Trastuzumab significantly reduced clinical and PET-detected tumour dimensions (P<0.01). An inverse association of tumour response with the percentage of cells expressing HIF1α at baseline was documented (P=0.01). Administration of Trastuzumab resulted in a decrease of the proliferation index (P=0.004), GLUT1 (P=0.04) and HER2 (P=0.01) expression. In contrast, the percentage of LC3A+/HER2+ cells was increased (P=0.01). High baseline HIF1α expression was the only parameter associated with poorer pathological response to preoperative chemotherapy (P=0.001).

Conclusions:

As the HER2+/LC3A+ phenotype, which often overexpresses HIF1α, is a major subpopulation increasing after therapy with Trastuzumab, LC3A- and HIF1α-targeting therapies should be investigated for the augmentation of anti-HER2 therapy efficacy.     

国际蛛网膜下腔出血动脉瘤试验:栓塞与夹闭后迟发性脑缺血的发生与影响(英文)

Delayed cerebral ischemia(DCI) is an important cause of poor outcome after aneurysmal subarachnoid hemorrhage(SAH).We studied differences in incidence and impact of DCI as defined clinically after coiling and after clipping in the International Subarachnoid Aneurysm Trial.We calculated odds ratios(OR) for DCI for clipping versus coiling with logistic regression analysis.With coiled patients without DCI as the reference group,we calculated ORs for poor outcome at 2 months and 1 year for coiled patients with DCI and for clipped patients without,and with DCI.With these ORs,we calculated relative excess risk due to Interaction(RERI).Clipping increased the risk of DCI compared to coiling in the 2,143 patients OR 1.24,95% confidence interval(95% CI 1.01-1.51).Coiled patients with DCI,clipped patients without DCI,and clipped patients with DCI all had higher risks of poor outcome than coiled patients without DCI.Clipping and DCI showed no interaction for poor outcome at 2 months: RERI 0.12(95% CI-1.16 to 1.40) or 1 year: RERI-0.48(95% CI-1.69 to 0.74).Only for patients treated within 4 days,coiling and DCI was associated with a poorer outcome at 1 year than clipping and DCI(RERI-2.02,95% CI-3.97 to-0.08).DCI was more common after clipping than after coiling in SAH patients in ISAT.Impact of DCI on poor outcome did not differ between clipped and coiled patients,except for patients treated within 4 days,in whom DCI resulted more often in poor outcome after coiling than after clipping.     

Children with ADHD show no deficits in plantar foot sensitivity and static balance compared to healthy controls

The goal of this study was to investigate plantar foot sensitivity and balance control of ADHD (n=21) impaired children compared to age-matched healthy controls (n=25). Thresholds were measured at 200Hz at three anatomical locations of the plantar foot area of both feet (hallux, first metatarsal head (METI) and heel). Body balance was quantified using the length, area and velocity described by the center of pressure (COP) during two-legged as well as one-legged stand (right and left legs). The comparison of vibration thresholds showed no differences between ADHD and healthy children at all anatomical locations of both feet. Whereas COP excursion and area were significantly lower in ADHD subjects compared to the healthy controls during two-legged stand, no differences were found in those variables when balancing on one leg. No differences in COP velocity between ADHD and healthy children were found in any analyzed conditions. The results indicate that the unusual and simple test situation may have increased the perception of vibration stimuli by the ADHD children. Furthermore, ADHD subjects seem to be less variable when performing simple tasks than healthy controls.     

Proxyfan acts as a neutral antagonist of histamine H3 receptors in the feeding-related hypothalamic ventromedial nucleus

BACKGROUND AND PURPOSE

Centrally acting histamine H₃ receptor ligands are proposed as potential treatments for obesity, although the value of inverse agonists at these receptors is still debated. Functional inhibition of H₃ autoreceptors activates neurones in a hypothalamic ‘satiety’ centre. The H₃ receptor antagonist, proxyfan was used as a tool to assess the action of histaminergic compounds in this model.

EXPERIMENTAL APPROACH

We compared the actions of histamine on feeding with those of an H₃ receptor agonist (imetit) and inverse agonist (thioperamide) in rats and mice. Sites of action were identified by immunohistochemistry and the hypothalamic ventromedial nucleus (VMN) was investigated using electrophysiological techniques.

KEY RESULTS

Central histamine or thioperamide decreased fast-induced feeding, whereas imetit increased feeding. Systemic thioperamide entered the brain to activate hypothalamic feeding centres and to reduce feeding without causing any adverse behaviours. Thioperamide activated neurones in the VMN through an action on histamine autoreceptors, whilst imetit had the opposite effect. Proxyfan administered alone did not affect either feeding or electrical activity. However, it blocked the actions of both thioperamide and imetit, acting as a neutral antagonist in this system.

CONCLUSIONS AND IMPLICATIONS

The H₃ receptor inverse agonist, thioperamide, potently reduced appetite without adverse behavioural effects. This action was blocked by proxyfan, acting as a neutral antagonist in this model and, therefore, this compound is useful in determining the selectivity of H₃ receptor-directed drugs. A major action of thioperamide is through presynaptic autoreceptors, inducing stimulation by endogenous histamine of postsynaptic H₁ receptors on anorectic hypothalamic neurones.     

Antibacterial activity of clarithromycin loaded PLGA nanoparticles

Novel drug delivery systems such as nanoparticles (NPs) have been proved to enhance the effectiveness of many drugs. Clarithromycin is a broad spectrum macrolide antibiotic, used in many infectious conditions like upper and lower respiratory tract infections, and skin and other soft tissue infections. This paper describes the preparation and enhanced in vitro antibacterial activities of clarithromycin loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles. A modified quasi-emulsion solvent diffusion (MQESD) method was used to prepare clarithromycin (CLR) NPs. The antibacterial activity of the NPs was evaluated using the agar well diffusion method against Escherichia coli (PTCC 1330), Haemophilus influenzae (PTCC 1623), Salmonella typhi (PTCC 1609), Staphylococcus aureus (PTCC 1112) and Streptococcus pneumoniae (PTCC 1240). The inhibition zone diameters related to each nano formulation were compared with those for untreated CLR at the same concentrations. The results indicated that the mean inhibition zone diameters of NPs against all the bacteria tested were significantly higher than those of untreated CLR, particularly in the case of S. aureus. The increased potency of CLR NPs may be related to some physicochemical properties of NPs like modified surface characteristics, lower drug degradation, and increased drug adsorption and uptake.     

Clinical evaluation of Deep Anterior Lamellar Keratoplasty (DALK) for stromal corneal opacities

Background

Corneal scars are commonly formed following many diseases of the eye like trauma, inflammation and infections. They lead to permanent diminution of vision which can be managed by Penetrating Keratoplasty (PK). PK is removing diseased as well as healthy tissues and is associated with many post-operative complications. Deep Anterior Lamellar Keratoplasty (DALK) is a relatively newer procedure which replaces only the diseased stroma, leaving the original corneal endothelium intact. This procedure is associated with lesser incidence of post-operative complications.

Methods

The study was conducted at a large tertiary care centre. 10 patients with stromal corneal scars were subjected to DALK and results were analysed after 06 months. Poor quality donor corneal tissue of B− and C grade was used in all cases.

Results

7 out of 10 patients (70%) undergoing DALK had post-operative visual acuity of 6/24 or better. 03 patients who did not have adequate recovery of visual acuity were due to over-riding of the graft in 01 case (10%), fungal keratitis in 01 case (10%) and interface haze in 01 case (10%).

Conclusion

DALK is a promising new technique for management of superficial corneal stromal scars using poor quality donor corneal tissue. Initial results are encouraging with minimal complications.     

Prevalence of malocclusion and orthodontic treatment need in schoolchildren – An epidemiological study

Background

To ascertain the prevalence of malocclusion and orthodontic treatment need in schoolchildren dependent on armed forces personnel. To review the overall oral health using DMFT index and to evaluate any relation between increased DMFT index to existing orthodontic problems.

Method

Five schools were randomly selected among Army/KV/AF schools and a random sample of 1200 children aged 10–15 years old attending these schools dependant on armed forces personnel were selected. A survey form was filled up after the examination of children by the principal worker and need for orthodontic treatment was assessed using index for orthodontic treatment need (IOTN) and overall oral health status by DMFT index and totaled. Frontal intra oral photograph in centric occlusion were taken. Dental Health Component (DHC) of IOTN for all the patients was marked by one set of orthodontists. The most severe occlusal trait was identified by the examiner for any particular patient and the patient was then categorized according to this most severe trait. AC of the IOTN was assessed by second orthodontist, individual and a layperson.

Results

It was observed that prevalence of malocclusion in the sample was 53.7%. 32.8% (239 males & 154 females) of samples are in need of orthodontic treatment. 55.1% of samples shown no caries risk, 38.1% had moderate caries risk and 6.8% had high caries risk.

Conclusion

Significant percentage of the samples are in need for orthodontic treatment. There is significant relation between higher DMFT index and orthodontic treatment need. It was found that IOTN is a reliable and user-friendly index, which can be used for orthodontic surveys.     

A novel application of contrast echocardiography to exclude active coronary perforation bleeding in patients with pericardial effusion

Management of hemodynamically significant cardiac tamponade will most often require pericardial drainage. In the absence of hemodynamic evidence of tamponade, however, management of a pericardial effusion represents a clinical dilemma. Pericardial leakage of blood may be transient, and extravasation may have stopped by time of echocardiographic assessment. Besides its usefulness in ischemic heart disease, contrast echocardiography might be applied in the context of coronary perforations. We report the use of contrast echocardiography in four cases of coronary perforation without overt signs of cardiac tamponade as a tool to streamline decision making as to whether perform pericardiocentesis or not. Our series demonstrate the clinical utility and effectiveness of echocardiographic contrast imaging to confirm or exclude active bleeding into the pericardial space when not otherwise visible by conventional imaging measures. © 2012 Wiley Periodicals, Inc.