Implants,Mechanical Devices,and Vascular Surgery for Erectile Dysfunction

IntroductionThe field of erectile dysfunction (ED) is evolving and there is a need for state-of-the-art information in the area of treatment.AimTo develop an evidence-based, state-of-the-art consensus report on the treatment of erectile dysfunction by implants, mechanical devices, and vascular surgery.MethodsTo provide state-of-the-art knowledge concerning treatment of erectile dysfunction by implant, mechanical device, and vascular surgery, representing the opinions of 7 experts from 5 countries developed in a consensus process over a 2-year period.Main Outcome MeasureExpert opinion was based on the grading of evidence-based medical literature, widespread internal committee discussion, public presentation, and debate.ResultsThe inflatable penile prosthesis (IPP) is indicated for the treatment of organic erectile dysfunction after failure or rejection of other treatment options. Comparisons between the IPP and other forms of ED therapy generally reveal a higher satisfaction rate in men with ED who chose the prosthesis. Organic ED responds well to vacuum erection device (VED) therapy, especially among men with a suboptimal response to intracavernosal pharmacotherapy. After radical prostatectomy, VED therapy combined with phosphodiesterase type 5 therapy improved sexual satisfaction in patients dissatisfied with VED alone. Penile revascularization surgery seems most successful in young men with absence of venous leakage and isolated stenosis of the internal pudendal artery following perineal or pelvic trauma. Currently, surgery to limit venous leakage is not recommended.ConclusionsIt is important for the future of the field that patients be made aware of all treatment options for erectile dysfunction in order to make an informed decision. The treating physician should be aware of the patient's medical and sexual history in helping to guide the decision. More research is needed in the area of revascularization surgery, in particular, venous outflow surgery. Hellstrom WJG, Montague DK, Moncada I, Carson C, Minhas S, Faria G, and Krishnamurti S. Implants, mechanical devices, and vascular surgery for erectile dysfunction.     

Onset of promiscuous gene expression in murine fetal thymus organ culture

T-cell differentiation and induction of tolerance to self-antigens occurs mainly in the thymus. Thymic stromal cells, specifically medullary thymic epithelial cells, express a diverse set of genes encoding parenchymal organ-specific proteins. This phenomenon has been termed promiscuous gene expression (PGE) and has been implicated in preventing organ-specific autoimmunity by inducing T-cell tolerance to self antigens. Early thymopoiesis and the critical factors involved in T-cell differentiation can be reproduced in vitro by murine fetal thymus organ culture (FTOC), which mimics the natural thymic microenvironment. To evaluate the occurrence of PGE in FTOC, gene expression profiling during in vitro thymic development in BALB/c mice was performed using a set of nylon cDNA microarrays containing 9216 sequences. The statistical analysis of the microarray data (sam program) revealed the temporal repression and induction of 57 parenchymal and seven lymphoid organ-specific genes. Most of the genes analysed are repressed during early thymic development (15-17 days post-coitum). The expression of the autoimmune regulator (AIRE) gene at 16 days post-coitum marks the onset of PGE. This precedes the induction of parenchymal organ genes during the late developmental phase at 20 days post-coitum. The mechanism of T-cell tolerance induction begins during fetal development and continues into adulthood. Our findings are significant because they show a fine demarcation of PGE onset, which plays a central role in induction of T-cell tolerance.     

Human cytomegalovirus glycoprotein B genotypes in Brazilian mothers and their congenitally infected infants

A case-control study design was used in order to compare the distribution of human cytomegalovirus (HCMV) glycoprotein B (gB) genotypes in 48 mothers of 49 congenitally infected infants with that observed in 144 mothers of 146 uninfected infants to study genetic variation of HCMV strains and maternal-fetal transmission. Congenital infection with HCMV was characterized by DNA detection and virus isolation from two urine or saliva samples collected prior to the third week of life. Genotyping of HCMV was carried out by a polymerase chain reaction-restriction fragment length polymorphism analysis of the variable region of the gB gene, testing for four genotypes. Genotype frequency was similar among the 28 non-transmitting mothers who were shedding virus (gB1: 25%; gB2: 28.6%; gB3: 42.8%; gB4: 0%), the 37 transmitting mothers (gB1: 21.6%; gB2: 46%; gB3: 27%; gB4: 0%), and the 49 infected infants (gB1: 39%; gB2: 37%; gB3: 24%; gB4: 0%). The same genotype was detected at different body sites (urine, saliva, and blood) of each infected newborn and in the respective mother (breast milk, urine, and saliva). Co-infection with multiple genotypes was observed in the immediate postpartum period in two mothers of infected infants (5.4%) and one non-transmitting mother (3.6%). The gB genotype was not correlated with intrauterine HCMV transmission. The genotype distribution found reflects the overall frequency of wild strains circulating in this geographic region. A single genotype is responsible for congenital HCMV infection. Co-infection with more than one strain, as characterized by gB genotype, was infrequent in women who were presumably immunocompetent.     

Inhibition of HIV-1 infection by monoclonal antibodies to carbohydrates of Schistosoma mansoni

Patients infected with HIV-1 develop a potent humoral immune response against the virus, but HIV-1 primary isolates are remarkably resistant to neutralizing antibodies. Considering that the envelope glycoprotein of HIV-1 (gp120/41) is heavily glycosylated, we investigated whether anti-carbohydrate antibodies could inhibit HIV-1 infection in vitro. We studied the neutralizing activity of three monoclonal antibodies (mAbs) raised to carbohydrates of Schistosoma mansoni, against seven primary isolates of HIV-1. Assays were performed infecting peripheral blood mononuclear cells from normal donors with viral isolates previously treated with mAbs. Viral strains used were tropic for the coreceptors CCR5, CXCR4, and dual-tropic ones. We found that the anti-glycan mAbs vigorously inhibited HIV-1 infection, regardless of the preferential coreceptor usage of the isolate, in a dose-response manner. Importantly, five isolates were resistant to neutralization by two HIV-1 antibody-positive human sera endowed with potent anti-HIV-1 inhibitory activity. Our findings suggest that carbohydrates of the HIV-1 viral envelope may be a target of an effective humoral immune response elicited by vaccination.The first two authors contributed equally to this work     

Association between matrix metalloproteinase (MMP)-2 polymorphisms and MMP-2 levels in hypertensive disorders of pregnancy

We examined whether two functional polymorphisms (g.-1306C>T and g.-735C>T) in matrix metalloproteinase (MMP)-2 gene are associated with preeclampsia (PE) or gestational hypertension (GH), and whether they modify MMP-2 or tissue inhibitor of metalloproteinase (TIMP)-2 plasma concentrations in these hypertensive disorders of pregnancy. We studied 130 healthy pregnant (HP), 130 pregnant with GH, and 133 pregnant with PE. Genomic DNA was extracted from whole blood and genotypes for g.-1306C>T and g.-735C>T polymorphisms were determined by Real Time-PCR, using Taqman allele discrimination assays. Haplotypes were inferred using the PHASE program. Plasma MMP-2 and TIMP-2 concentrations were measured by ELISA. The main findings were that pregnant with PE have higher plasma MMP-2 and TIMP-2 concentrations than HP (P<0.05), although the MMP-2/TIMP-2 ratios were similar (P>0.05). Moreover, pregnant with GH have elevated plasma MMP-2 levels and MMP-2/TIMP-2 ratios compared to HP (P<0.05). While MMP-2 genotypes and haplotypes are not linked with hypertensive disorders of pregnancy, MMP-2 genotypes and haplotypes are associated with significant alterations in plasma MMP-2 and TIMP-2 concentrations in preeclampsia (P<0.05). Our findings may help to understand the relevance of MMP-2 and its genetic polymorphisms to the pathophysiology of hypertensive disorders of pregnancy. It is possible that patients with PE and the MMP-2 haplotype combining the C and T alleles for the g.-1306C>T and g.-735C>T polymorphisms may benefit from the use of MMPs inhibitors such as doxycycline. However, this possibility remains to be determined.     

Gene analysis in patients with premature ovarian failure or gonadal dysgenesis: a preliminary study

OBJECTIVE: The aim of this study was to evaluate the presence of mutations in the coding region of the QM gene and fragile X in patients with premature ovarian failure and gonadal dysgenesis. METHODS: After approval by the local Ethics Committee, blood samples, in EDTA, of 100 normally ovulating women, 23 with premature ovarian failure (POF) and 14 with gonadal dysgenesis 46XX, aged less than 40 years, were screened for mutation in the QM gene coding region. All patients with POF have 46, XX karyotype and serum levels of follicle-stimulating hormone (FSH) over 30 mIU/mL. In addition, all samples from patients with premature ovarian failure underwent analysis for fragile X. RESULTS: The QM gene located at a hotspot region (Xq28) showed five points of mutations in a patient with premature ovarian failure. Four of them were able to change the amino acid sequence of the protein. None of our patients were diagnosed as having pre or mutant X fragile syndrome. CONCLUSION: Our study suggests that Xq28 (QM gene) may be involved in ovary failure. However, further studies are needed to confirm this hypothesis.     

Relevance of skip metastases for squamous cell carcinoma of the oral tongue and the floor of the mouth.

OBJECTIVE: To analyze the therapeutic implications of the distribution of neck metastases (NM) in patients with squamous cell carcinoma (SCC) of the tongue and the floor of the mouth (FOM). PATIENTS AND METHODS: From January 1987 through December 1997, 339 previously untreated patients with T1-2 N0 M0 SCC of the tongue and the FOM underwent primary surgical treatment in our institution. A retrospective review of the pathology reports and outcome of these patients was made to ascertain the prevalence and distribution of NM. Patients were grouped by clinical neck status at the time of neck dissection: elective neck dissection (END) in the NO neck and subsequent therapeutic dissection (STD) in the neck observed which converted clinically to N+ or regional recurrences after END. All patients were classified according to the American Joint Committee on Cancer (AJCC)/UICC 2002 TNM classification. RESULTS: All patients underwent surgical treatment of the primary cancer and had negative margins at frozen section. Overall incidence of NM was 41.3%. Twenty-seven point eight percent of T1 N0 M0 and 48.2% of T2 N0 M0 patients developed NM (P = .0004). Occult neck metastases occurred in 24.1% of patients. Clinically, N+ metastases occurred in 23.6% of patients. The overall incidence of NM in levels IV and V was 8.5%. Neck level IV nodes were involved in only 1.5% of patients in the END group versus 23.7% in the STD group (P < 0.001). Level V was always associated to nodal metastases in other neck levels. Only 2% of patients in our study presented "skip metastases" in the neck. CONCLUSIONS: Neck levels I and II were at great risk for the development of NM (46.9% and 75.3% respectively). Levels IV (6.5%) and V (2%) were rarely involved in our group of patients. The results found in this study support the indication of supraomohyoid neck dissection for N0 and a more comprehensive neck dissection (levels I-V) for N+ patients in Stage I-II SCC of the tongue and FOM. EBM rating: C-4.     

MC3T3‐E1 Cells Behavior on Surfaces Bombarded by Argon Ions in Planar Cathode Discharge

To evaluate the effect of topography in nanoscale, titanium surfaces were bombarded by argon ions (a chemically inert gas), in an atmosphere of plasma. The effects of surface parameters on morphology, adhesion, proliferation, and MC3T3‐E1 preosteoblasts differentiation were analyzed. Nontreated (smooth) surfaces were used as a control. The levels of average roughness (Ra) observed in bombarded and smooth titanium surfaces were of 95 and 14 nm, respectively. The wettability increased on treated surfaces. The number of attached cells (30 and 60 min) was significantly higher on the bombarded surface. The cell proliferation after 3 and 7 days was also significantly higher on the ion‐bombarded surface. In addition, the ALP activity and expression of osteocalcin were higher in cells grown on the treated surface. The results showed that bombardment with argon ions increased the roughness and the wettability of the Ti surface, promoting a significant increase in the adhesion, proliferation, and differentiation of preosteoblasts.