Incremental value of arterial wave reflections in the determination of left ventricular diastolic dysfunction in untreated patients with essential hypertension

Systemic arterial stiffness is an indicator of cardiovascular disease and an independent marker of morbidity and cardiovascular mortality. We investigated the association of arterial wave reflections with left ventricular (LV) diastolic dysfunction and their incremental value to other determinants of LV diastolic dysfunction in patients with essential hypertension. In total 143 patients and 20 controls with similar atherosclerotic risk factors were examined by applanation tonometry of the radial artery (Sphygmocor) and echocardiography. Central augmentation index (CAI%) of reflected arterial waves as well as aortic strain (AoS) assessed by echocardiography were estimated. Doppler diastolic abnormalities were defined as proposed by the European Study Group on diastolic heart failure by measurement of E/A ratio (the ratio of the mitral inflow velocities), isovolumic relaxation time, deceleration time and flow propagation velocity. AoS and CAI were impaired in patients compared with controls (4.67 +/- 2.94 vs 6.06 +/- 4.91% and 145.8 +/- 22.7 vs. 135.7 +/- 20.3%, P < 0.01) as well as in patients with LV diastolic dysfunction compared to patients without, (5.52 +/- 4.29 vs. 10.73 +/- 5.77% and 139.5 +/- 21.7 vs. 124.5 +/- 17.0%, P < 0.05). The odds ratio (OR) of AoS and CAI for diastolic dysfunction was OR:0.918, 95% confidence interval (CI):0.837-0.99, P = 0.04 and OR:1.023, 95% CI: 1.023-1.040 P = 0.010, respectively. The addition of CAI to the multivariable model including age, LV mass index, AoS and mean arterial pressure increased the power of the model for determination of LV diastolic dysfunction (-2 log likelihood = 139.368, change of chi2 = 4.2, P-value for change=0.04). In untreated patients with newly diagnosed essential hypertension, wave reflections are independent and additive determinants of LV diastolic dysfunction.     

Sexual dysfunction in testicular cancer patients subjected to post‐chemotherapy retroperitoneal lymph node dissection: a focus beyond ejaculation disorders

Post‐chemotherapy retroperitoneal lymph node dissection (PC‐RPLND) represents an integral part of multidisciplinary treatment of advanced germ cell cancer; however, it is associated with a high complications rate. The present study aimed to describe sexual disorders in 53 patients with testicular cancer who underwent full bilateral, non‐nerve‐sparing PC‐RPLND in our institution, focusing beyond ejaculatory dysfunction. The International Index for Erectile Function (IIEF) questionnaire was used as diagnostic tool of male sexual functioning pre‐operatively and three months after RPLND, while post‐operatively patients were asked to describe and evaluate changes in selected sexual parameters. Study findings demonstrate mixed pattern of changes in sexual functioning, with no difference in erectile functioning before and after operation. However, orgasmic function and intercourse and overall sexual satisfaction were found significantly impaired post‐operatively. Sexual desire and frequency of attempted sexual intercourses were found significantly increased post‐operatively, in comparison with pre‐operative levels. With regard to patients' subjective perception on sexual functioning alterations after PC‐RPLND, a significant number of patients reported higher levels of sexual desire, no difference in erectile function and worse orgasmic function and satisfaction post‐operatively. Thus, patients subjected to PC‐RPLND should be closely and routinely evaluated due to close relationship of sexual dissatisfaction with secondary psychological disorders.     

The clinicopathological and prognostic significance of membrane type 1 matrix metalloproteinase (MT1-MMP) and MMP-9 according to their localization in invasive breast carcinoma

AIMS: To investigate the clinicopathological and prognostic significance of membrane type 1 matrix metalloproteinase (MT1-MMP) and MMP-9 proteins expression in invasive breast carcinoma and their relationship to tumour proliferation and expression of c-erbB2 and peroxisome proliferator-activated receptor (PPAR) gamma. METHODS: Immunohistochemistry was carried out on 175 paraffin-embedded breast tissue specimens to detect MT1-MMP, MMP-9, oestrogen receptor (ER), progesterone receptor, c-erbB-2, Ki67, topoisomerase IIalpha (topo IIalpha) and PPARgamma protein expression. RESULTS: Both MT1-MMP and MMP-9 were expressed in the cytoplasm of the malignant cells and the peritumoral stroma. Cytoplasmic MT1-MMP was more often observed in ER+ tumours (P = 0.022), of a lower nuclear grade (P = 0.020) and with reduced expression of Ki67 and topo IIalpha (P = 0.027 and P = 0.006, respectively). Moreover, cytoplasmic MT1-MMP was positively associated with MMP-9 (P = 0.010) and PPARgamma (P < 0.0001). Cytoplasmic MMP-9 was inversely associated with Ki67 (P = 0.034) and topo IIalpha (P = 0.004), whereas its relationship with MT1-MMP (P = 0.034) and PPARgamma (P = 0.024) was found to be positive. Stromal MMP-9 was more often observed in c-erbB2+ tumours (P = 0.043) and had an unfavourable impact on overall and relapse-free survival in both univariate (P = 0.0157 and P = 0.0274, respectively) and multivariate analyses (P = 0.007 and P = 0.024, respectively). CONCLUSIONS: Cytoplasmic MT1-MMP and MMP-9 seem to be related to well-differentiated tumours, with a low proliferation potential, while stromal MMP-9 is associated with an aggressive tumour phenotype and is recognized as an independent poor prognostic indicator.     

Increased cortical neuronal responses to NMDA and improved attentional set-shifting performance in rats following prebiotic (B-GOS®) ingestion

We have previously shown that prebiotics (dietary fibres that augment the growth of indigenous beneficial gut bacteria) such as Bimuno^? galacto-oligosaccharides (B-GOS^®), increased N-methyl-D-aspartate (NMDA) receptor levels in the rat brain. The current investigation examined the functional correlates of these changes in B-GOS^®-fed rats by measuring cortical neuronal responses to NMDA using in vivo NMDA micro-iontophoresis electrophysiology, and performance in the attentional set-shifting task. Adult male rats were supplemented with B-GOS^® in the drinking water 3 weeks prior to in vivo iontophoresis or behavioural testing. Cortical neuronal responses to NMDA iontophoresis, were greater (+30%) in B-GOS^® administered rats compared to non-supplemented controls. The intake of B-GOS^® also partially hindered the reduction of NMDA responses by the glycine site antagonist, HA-966. In the attentional set-shifting task, B-GOS^® -fed rats shifted from an intra-dimensional to an extra-dimensional set in fewer trials than controls, thereby indicating greater cognitive flexibility. An initial exploration into the mechanisms revealed that rats ingesting B-GOS^® had increased levels of plasma acetate, and cortical GluN2B subunits and Acetyl Co-A Carboxylase mRNA. These changes were also observed in rats fed daily for 3 weeks with glyceryl triacetate, though unlike B-GOS^®, cortical histone deacetylase (HDAC1, HDAC2) mRNAs were also increased which suggested an additional epigenetic action of direct acetate supplementation. Our data demonstrate that a pro-cognitive effect of B-GOS^® intake in rats is associated with an increase in cortical NMDA receptor function, but the role of circulating acetate derived from gut bacterial fermentation of this prebiotic requires further investigation.     

PCaGuard: A Software Platform to Support Optimal Management of Prostate Cancer

Background and Objective  Prostate cancer (PCa) is a severe public health issue and the most common cancer worldwide in men. Early diagnosis can lead to early treatment and long-term survival. The addition of the multiparametric magnetic resonance imaging in combination with ultrasound (mpMRI-U/S fusion) biopsy to the existing diagnostic tools improved prostate cancer detection. Use of both tools gradually increases in every day urological practice. Furthermore, advances in the area of information technology and artificial intelligence have led to the development of software platforms able to support clinical diagnosis and decision-making using patient data from personalized medicine. Methods  We investigated the current aspects of implementation, architecture, and design of a health care information system able to handle and store a large number of clinical examination data along with medical images, and produce a risk calculator in a seamless and secure manner complying with data security/accuracy and personal data protection directives and standards simultaneously. Furthermore, we took into account interoperability support and connectivity to legacy and other information management systems. The platform was implemented using open source, modern frameworks, and development tools. Results  The application showed that software platforms supporting patient follow-up monitoring can be effective, productive, and of extreme value, while at the same time, aiding toward the betterment medicine clinical workflows. Furthermore, it removes access barriers and restrictions to specialized care, especially for rural areas, providing the exchange of medical images and patient data, among hospitals and physicians. Conclusion  This platform handles data to estimate the risk of prostate cancer detection using current state-of-the-art in eHealth systems and services while fusing emerging multidisciplinary and intersectoral approaches. This work offers the research community an open architecture framework that encourages the broader adoption of more robust and comprehensive systems in standard clinical practice.     

Urgent superselective segmental renal artery embolization in the treatment of life-threatening renal hemorrhage

INTRODUCTION: Renal hemorrhage is a major life-threatening condition that can be caused by trauma, operation, biopsy, as well as sudden spontaneous rupture of renal tumors or aneurysms. We report our experience with superselective segmental renal artery catheterization and embolization as therapeutic options for such cases. PATIENTS AND METHODS: Over the last 8 years, 28 patients with severe renal hemorrhage were admitted for evaluation and possible further treatment. Twenty of them had a history of previous biopsy (6 of them one of a transplanted kidney), 1 patient had a recent percutaneous nephrostomy, 4 patients presented with renal mass ruptures (2 patients renal cell carcinoma, 1 patient angiomyolipoma, 1 patient hemorrhagic cysts), 1 patient had rupture of a renal aneurysm during delivery, 1 patient suffered bleeding after partial nephrectomy, and 1 patient was hospitalized after a car accident. They all presented with clinical signs of hemodynamic instability. Angiographic investigation of the kidneys preceded further intervention in all cases. 26 out of the 28 patients underwent superselective embolization of the specific bleeding vessel with the use of microcoils and/or Gelfoam particles. RESULTS: All patients treated by superselective segmental renal artery embolization had a successful outcome, including a steady renal function and a stable clinical course. No complications occurred. CONCLUSION: Superselective segmental renal artery catheterization and embolization is a safe and efficient method for the treatment of patients with severe renal hemorrhage, preserving healthy renal parenchyma and renal function.     

Diagnostic steps in the evaluation of patients with erectile dysfunction

PURPOSE: The necessity for a thorough diagnostic evaluation for erectile dysfunction has been questioned after the availability of effective oral therapies. We determined the impact of the different diagnostic steps on the management strategy for erectile dysfunction. MATERIALS AND METHODS: The study included all patients who presented at an andrology outpatient clinic during a 4-year period. Baseline evaluation included medical and sexual history, blood tests, physical examination and intracavernous injection test. Patients with normal initial screening were evaluated with specific diagnostic procedures. The results were analyzed to identify the diagnostic potential of each screening step separately. RESULTS: Overall 1,644 patients presented at the clinic during the study period, of whom 368 (22.4%) were excluded from study due to severe psychiatric (5.2%) or cardiovascular (2.7%) disease, or to a history of erectile dysfunction less than 3 months in duration (14.5%). In the remaining 1,276 patients with a mean age plus or minus standard deviation of 56 +/- 14 years, and a mean duration of erectile dysfunction of 4.9 +/- 3.4 years medical history revealed erectile dysfunction associated medical conditions in 57%, blood tests identified previously undiagnosed medical conditions in 6.2%, and physical examination and the intracavernous injection test were diagnostic in 13.9% and 2.6%, respectively. Initial screening was negative in 259 cases (20.3%), in which specific diagnostic procedures identified an underlying vascular pathology in 165 (12.9%) and unfavorable penile geometry in 16 (1.3%). The remaining 78 men (6.1%) had no evidence of organic disease. CONCLUSIONS: Baseline diagnostic evaluation for erectile dysfunction can identify the underlying pathological condition or erectile dysfunction associated risk factors in 80% of patients. Such screening may diagnose reversible causes of erectile dysfunction and also unmask medical conditions that manifest with erectile dysfunction as the first symptom. Specific diagnostic procedures may be limited in patients with primary erectile dysfunction or those without risk factors. Such clinical data support previously published guidelines for erectile dysfunction management.     

Management strategy for arterial priapism: therapeutic dilemmas

PURPOSE: We present 7 cases of arterial high flow priapism and propose management algorithms for the condition. MATERIALS AND METHODS: We studied 2 children and 5 adults with posttraumatic arterial priapism. Blood gas analysis and color Doppler ultrasonography of the corpora cavernosa confirmed the diagnosis in 4 adults, while 1 patient had already undergone cavernous artery ligation in elsewhere. In the children perineal compression resulted in detumescence, a sign that is proposed to be indicative of the diagnosis of arterial priapism (piesis sign) complementing physical examination. Mechanical compressive force was applied to the perineum of 1 boy, while the other received a watchful waiting program. All adults participated in an observation regimen except 1, who decided to undergo immediate embolization of the internal pudendal artery. RESULTS: Perineal compression led to the resolution of priapism in 1 child, while spontaneous resolution was noted in the other. An adult noticed spontaneous penile detumescence 3 to 4 months after trauma, which was attributable to site specific venous leakage and decreased, inflow in the contralateral cavernous artery. The patient underwent venous surgery and is on an intracavernous injection regimen. Successful embolization of the internal pudendal artery was performed immediately in 1 man and in the other 4 months after trauma due to social inconvenience. Adult patient 3 is still on the watchful waiting protocol (42 months), while the one who underwent cavernous artery ligation is receiving treatment for erectile dysfunction. CONCLUSIONS: Absent of long-term damaging effects of arterial priapism on erectile tissue combined with the possibility of spontaneous resolution or progressive concomitant hemodynamic abnormalities associated with blunt perineal trauma are suggestive of the introduction of an observation period in the management algorithm of high flow priapism. Such a period may help avoid unnecessary intervention and determine the impact of priapism on patient personal life. Perineal compression may be also added as part of the physical examination as a sign specifically indicative of arterial priapism.     

Role of alpha7 nicotinic receptors in nicotine dependence and implications for psychiatric illness

It has previously been shown that the reinforcing and dependence-producing properties of nicotine depend to a great extent on activation of nicotinic receptors within the ventral tegmental area (VTA), i.e. the site of origin of the mesolimbocortical dopaminergic projection. Based on the data reviewed in the present study, it is suggested that nicotine by stimulating presynaptic alpha7 nicotinic receptors within the VTA, that are probably localized on glutamatergic afferents from the medial prefrontal cortex, produces sequentially an increase in glutamate concentrations, stimulation of NMDA receptors found on dopamine (DA)-containing neurons in the VTA, enhanced firing activity of VTA-DA neurons, augmented DA release in the nerve terminal regions, and enhanced c-fos expression in the dopaminergic projection areas through activation of D1-DA receptors. In addition, it appears that alpha7 nicotinic receptors within the VTA are directly involved in nicotine-related reward and withdrawal responses. These data may be instrumental in understanding how nicotine interacts with the mesolimbocortical dopaminergic system, which is perhaps the most important component of the neural mechanisms underlying nicotine dependence. These results may also contribute to unraveling the cellular basis of nicotine's association with neuropsychiatric disorders, thereby offering the prospect of new therapeutic advances for their treatment.     

Effects of acute and subchronic d-amphetamine on ventral striatal concentrations of neurotensin and neuropeptide Y in rats treated with antipsychotic drugs

We have reported that acute d-amphetamine increases extracellular concentrations (efflux) of neurotensin-like immunoreactivity (NT-LI) and neuropeptide Y-LI (NPY-LI) in the ventral striatum (VSTR) of freely moving rats, effects that are abolished by chronic administration of haloperidol and risperidone admixed to food pellets. In this study we further investigated the d-amphetamine effects on NT-LI and NPY-LI efflux in VSTR and their content in selected brain regions. Rats received haloperidol, risperidone or vehicle for 30 days and saline or d-amphetamine either on days 22–29 and/or day 30. Seven day d-amphetamine administration decreased basal NT-LI and NPY-LI efflux in vehicle-treated rats; pretreatment with haloperidol counteracted these effects, while pretreatment with risperidone had effect only on NT-LI. Acute d-amphetamine after the seven day d-amphetamine increased NT-LI only. Pretreatment with haloperidol or risperidone abolished the effects of acute d-amphetamine on NT-LI and NPY-LI. Acute and seven day d-amphetamine increased NT-LI and NPY-LI contents in striatum; seven day d-amphetamine also increased NT-LI in frontal and occipital cortex and both NT-LI and NPY-LI in hippocampus. Our results suggest that NT and NPY are involved in both the pathophysiology and the therapeutics of schizophrenia.