Three-year outcome following holmium laser enucleation of the prostate combined with mechanical morcellation in 330 consecutive patients

OBJECTIVES: A prospective study to assess safety, efficacy, and medium-term durability of holmium laser enucleation of the prostate (HoLEP) combined with mechanical morcellation for the treatment of bladder outlet obstruction (BOO) due to benign prostate enlargement (BPE). METHODS: Between January 2000 and July 2003, 330 consecutive patients underwent HoLEP at our institution. All patients were pre-operatively assessed with transrectal ultrasound gland volume evaluation, maximum urinary flow rate (Q(max)), international prostate symptoms score (IPSS), and the single-question quality of life (QoL). Intra-, peri-, and postoperative parameters were evaluated and the patients were reassessed at 1-, 3-, 6-, 12-, 18-, 24-, and 36-mo follow-up with the same examinations. RESULTS: Patients' mean age was 66+/-8.1 yr; prostate volume was 62+/-34 cc. Enucleation time was 45.4+/-22.9 min and morcellation time 17.3+/-14 min, whilst resected weight was 40+/-27.5 g. Catheter time was 23+/-14.7h and hospital stay was 48+/-26 h. Mean serum hemoglobin and sodium did not drop significantly from baseline after the procedure (p=013). A significant improvement occurred in Q(max) (25.1+/-10.7 ml/s), IPSS (0.7+/-1.3), and QoL (0.2+/-0.5) at the 3-yr follow-up compared with baseline (p<0.05). Twenty-eight percent of patients complained of irritative urinary symptoms, typically self-limiting after 3 mo; transient stress incontinence was reported in 7.3% of patients. Nine patients (2.7%) had persistent BOO, requiring reoperation. CONCLUSIONS: HoLEP represents an effective and safe surgical intervention. The relief from BOO also proved to be durable after 3-yr follow-up. The present report adds to the evidence that HoLEP could be the standard "size-independent" surgical treatment for symptomatic BPE-related BOO.     

Human infection with Cryptosporidium felis: case report and literature review.

An infection with Cryptosporidium felis in an HIV-positive man from Italy was successfully treated with paromomycin, despite the patient's having a CD4+ cell count of 31/mL. Fourteen cases of human infection with C. felis have been described, all in the past 3 years, emphasizing the public health importance of Cryptosporidium parasites other than C. parvum.     

A Review of the Ahmed Glaucoma Valve Implant and Comparison with Other Surgical Operations

The Ahmed glaucoma valve (AGV) is a popular glaucoma drainage implant used for the control of intraocular pressure in patients with glaucoma. While in the past AGV implantation was reserved for glaucoma patients poorly controlled after one or more filtration procedures, mounting evidence has recently encouraged its use as a primary surgery in selected cases. AGV has been demonstrated to be safe and effective in reducing intraocular pressure in patients with primary or secondary refractory glaucoma. Compared to other glaucoma surgeries, AGV implantation has shown favorable efficacy and safety. The aim of this article is to review the results of studies directly comparing AGV with other surgical procedures in patients with glaucoma.     

Out-of-hospital cardiac arrest caused by transient left ventricular apical ballooning syndrome

We describe a case of out-of-hospital cardiac arrest due to ventricular fibrillation in a patient with transient left ventricular apical ballooning syndrome. Our report confirms that left ventricular apical ballooning may have the same complications of myocardial infarction, adding the early ventricular fibrillation to the previous findings of left ventricular wall rupture, ventricular arrhythmias during hospitalization and complete atrio-ventricular block. Moreover, left ventricular apical ballooning may have different and unusual clinical onsets, including sudden cardiac death due to ventricular tachyarrhythmias in the absence of associated symptoms. Therefore, in our opinion left ventricular apical ballooning may be considered as a possible cause of sudden death in otherwise healthy women.     

Improvement of interleukin 2 production,clonogenic capability and restoration of stromal cell function in human immunodeficiency virus-type-1 patients after highly active antiretroviral therapy

Haematological abnormalities frequently occur in patients infected by human immunodeficiency virus-type 1 (HIV-1). Increasing evidence indicates that bone marrow suppression (BM) results from viral infection of accessory cells, with impaired stromal function and alteration of haematopoietic growth factor network. We have investigated the effects of antiretroviral therapy on cytokine and chemokine production by BM cells and stromal cells in a group of HIV-1-infected subjects before and during treatment. Compared with uninfected controls, an altered cytokine and chemokine production by BM cells was observed before treatment, characterized by decreased interleukin 2 (IL-2) and elevated tumour necrosis factor-alpha, macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, and RANTES (regulated on activation, normal T cell-expressed and secreted) levels, along with a defective BM clonogenic activity. Antiretroviral therapy showed increased BM clonogenic capability, associated with normalization of IL-2 production and chemokine receptors expression on CD34+ cells. Pre-therapy, BM accessory cells were represented by macrophage-like cells, in some cases positive for HIV-1 DNA, suggesting that these cells are the main target of HIV-1 infection. During therapy, the stromal cells became predominantly fibroblastoid-like, as observed in normal controls, and were negative for HIV-1 DNA. Controlling HIV-1 replication may produce amelioration of stem cell activity, and restoration of stromal cell pattern and functions, with increased IL-2 production at BM level.     

Acute migraine in the Emergency Department: extending European principles of management

The World Health Organization (WHO) placed migraine 19th among all causes of disability (12th in women) measured in years of healthy life lost to disability (YLD). The importance of headache disorders, particularly of the primary forms, is established by their distribution worldwide, their duration (the majority being life-long conditions) and their imposition of both disability and life-style restrictions among large numbers of people. For these reasons, headache disorders should represent a public-health priority. In the Emergency Department (ED), as elsewhere, migraine is often under-diagnosed-and under-treated when it is diagnosed. The result is likely to be failure of treatment. Particular attention to diagnosis is needed in ED patients with acute headache, since there is a higher probability of secondary headache due to underlying pathologies. According to European principles of management, acute migraine treatment generally is stepwise. Of the two main steps, the first relies on symptomatic medication, preferably NSAIDs with or without antiemetics. The second step uses specific therapies, usually triptans. Modifications to routine practice are appropriate in the ED. Parenteral administration of symptomatic therapies is a preferred first choice, whilst immediate resort to triptans may be appropriate, and achieve better outcomes, in patients with severe headache and diagnostic confirmation of migraine.     

Polypharmacology of small molecules targeting the ubiquitin–proteasome and ubiquitin-like systems

Targeting the ubiquitin–proteasome system (UPS) and ubiquitin-like signalling systems (UBL) has been considered a promising therapeutic strategy to treat cancer, neurodegenerative and immunological disorders. There have been multiple efforts recently to identify novel compounds that efficiently modulate the activities of different disease-specific components of the UPS-UBL. However, it is evident that polypharmacology (the ability to affect multiple independent protein targets) is a basic property of small molecules and even highly potent molecules would have a number of “off target” effects. Here we have explored publicly available high-throughput screening data covering a wide spectrum of currently accepted drug targets in order to understand polypharmacology of small molecules targeting different components of the UPS-UBL. We have demonstrated that molecules targeting a given UPS-UBL protein also have high odds to target a given off target spectrum. Moreover, the off target spectrum differs significantly between different components of UPS-UBL. This information can be utilized further in drug discovery efforts, to improve drug efficiency and to reduce the risk of potential side effects of the prospective drugs designed to target specific UPS-UBL components.     

Phosphoinositide 3-kinase gamma-deficient hearts are protected from the PAF-dependent depression of cardiac contractility

OBJECTIVES: Following an ischemic insult, cardiac contractile recovery might be perturbed by the release of autacoids, like platelet-activating factor (PAF), that depress heart function by acting through G protein-coupled receptors (GPCRs). The signaling events downstream the PAF receptor that lead to the negative inotropic effect are still obscure. We thus investigated whether the GPCR-activated phosphoisositide 3-kinase gamma (PI3Kgamma) could play a role in the cardiac response to PAF. METHODS: The negative inotropic effect of PAF was studied ex vivo, in isolated electrically driven atria and in Langendorff-perfused whole hearts derived from wild-type and PI3Kgamma-null mice. Postischemic recovery of contractility was analyzed in normal and mutant whole hearts subjected to 30 min of ischemia and 40 min of reperfusion in the presence or absence of a PAF receptor antagonist. RESULTS: While wild-type hearts stimulated with PAF showed increased nitric oxide (NO) production and a consequent decreased cardiac contractility, PI3Kgamma-null hearts displayed reduced phosphorylation of nitric oxide synthase 3 (NOS3), blunted nitric oxide production and a complete protection from the PAF-induced negative inotropism. In addition, Langendorff-perfused PI3Kgamma-null hearts showed a better contractile recovery after ischemia/reperfusion, a condition where PAF is known to be an important player in depressing contractility. In agreement with a role of PI3Kgamma in this PAF-mediated signaling, postischemic contractile recovery in PI3Kgamma-null mice appeared overlapping with that of normal hearts treated with the PAF receptor antagonist WEB 2170. CONCLUSION: These data indicate a novel PAF-dependent signaling pathway that, involving PI3Kgamma and NOS3, contributes to postischemic contractile depression.     

Molecular Imaging of Neuroblastoma Progression in TH-MYCN Transgenic Mice

Purpose

TH-MYCN transgenic mice represent a valuable preclinical model of neuroblastoma. Current methods to study tumor progression in these mice are inaccurate or invasive, limiting the potential of this murine model. The aim of our study was to assess the potential of small animal positron emission tomography (SA-PET) to study neuroblastoma progression in TH-MYCN mice.

Procedure

Serial SA-PET scans using the tracer 2-deoxy-2-[¹⁸F]fluoro-d-glucose (¹⁸F-FDG) have been performed in TH-MYCN mice. Image analysis of tumor progression has been compared with ex vivo evaluation of tumor volumes and histological features.

Results

[¹⁸F]FDG-SA-PET allowed to detect early staged tumors in almost 100 % of TH-MYCN mice positive for disease. Image analysis of tumor evolution reflected the modifications of the tumor volume, histological features, and malignancy during disease progression. Image analysis of TH-MYCN mice undergoing chemotherapy treatment against neuroblastoma provided information on drug-induced alterations in tumor metabolic activity.

Conclusions

These data show for the first time that [¹⁸F]FDG-SA-PET is a useful tool to study neuroblastoma presence and progression in TH-MYCN transgenic mice.