Search

The primary objective of this study was to correlate simultaneous measures of prostate-specific antigen (PSA) and serum testosterone among large samples of eugonadal, untreated hypogonadal and hypogonadal men treated with testosterone replacement therapy (TRT). From 2001 to 2007, laboratory records were reviewed to identify men who underwent simultaneous measurement of PSA and serum testosterone levels. The data were stratified based on three groups of men: group 1 consisted of eugonadal men (T>300 ng per 100 ml) evaluated for BPH, reproductive failure or sexual dysfunction; group 2 consisted of untreated hypogonadal men (T<300 ng per 100 ml); and group 3 comprised symptomatic hypogonadal men receiving TRT. Correlations were found between PSA (total and free fractions) and total serum testosterone levels among the three groups. Group 1: eugonadal men (n=385 patients), mean PSA and serum testosterone were 1.60 ng ml−1 and 484 ng 100 ml, respectively. There was no significant correlation between PSA and total serum testosterone levels (r=−0.01, P=0.8). Group 2: untreated hypogonadal men (n=229 patients), mean PSA and serum testosterone were 1.49 ng ml−1 and 269 ng per 100 ml, respectively. There was no significant correlation between PSA and total serum testosterone levels (r=0.03, P=0.6). Group 3: hypogonadal men on TRT (n=229 patients and 994 individual samples analyzed) mean PSA and serum testosterone were 1.50 ng ml−1 and 555 ng per 100 ml, respectively. There was no significant correlation between PSA and serum testosterone levels (r=−0.005, P=0.9). Mean total serum testosterone levels were increased significantly (P<0.001) following treatment. Mean PSA levels did not increase in a statistically or clinically significant manner following TRT (mean PSA increase from baseline 0.05 ng ml−1, P=0.6). In conclusion, TRT does not appear to significantly influence serum PSA expression and no significant correlation was identified between PSA and serum testosterone among eugonadal, untreated hypogonadal and hypogonadal men receiving TRT.International Journal of Impotence Research (2008) 20, 561–565; doi:10.1038/ijir.2008.40; published online 9 October 2008 [ABSTRACT FROM AUTHOR]

Objective To investigate the factors that may affect antibody titres to heat shock proteins (Hsp)‐60, ‐65 and ‐70, and serum C‐reactive protein (CRP) concentrations in patients with dyslipidaemia and other features of the metabolic syndrome as defined by ATPIII criteria. Material and methods . The study comprised 237 dyslipidaemia patients and 135 healthy individuals recruited from amongst university and hospital employees. Results . Compared to the healthy individuals, the dyslipidaemic patients had higher antibody titres to Hsp‐60 ( p [ABSTRACT FROM AUTHOR]

To investigate the variation in post-cure palatal discrepancy of dentures, 20 complete maxillary replica dentures were prepared on models with high and low palates and processed by conventional compression moulding and injection moulding. Measurements were made by travelling microscope of the sagittal midline discrepancies between palate and model on three occasions; after processing; after removal of part of the investing plaster; and after immersion in water for 1 month at 37 °C. The magnitudes of discrepancies were greatest distally, diminishing with distance anteriorly from the postdam. They increased with partial removal of plaster, and decreased slightly after immersion. [ABSTRACT FROM AUTHOR]

A study was carried out to establish the relative need for treatment of a range of defects of dental appearance and identify differences between individual and group assessments. Three groups (n = 42), two of patients (one referred for a defect of dental appearance and one not) and one of dental students, assessed urgency of need on a visual analogue scale (VAS), of four cases of dental defect presented as colour prints. All groups rated the need for treatment of the four cases in the same order. Data sets were non-normal with wide ranges. Patients without a defect of appearance usually assessed treatment need as significantly less urgent. Marked variation was discovered between individual assessments within otherwise similar groups. Based on group decisions, guidelines for treatment of defects of dental appearance could be established. However, so extreme are individual variations that very sympathetic application would be needed if dissatisfaction is not to result. [ABSTRACT FROM AUTHOR]

Investigates the relationship between anti-heat shock protein-60/65 (HSP) immune responses, endothelial dysfunction and atherosclerosis in the chronic low-level hypercholesterolaemic rabbit model using the Calmette-Guerin (BCG) immunization. Rise in plasma level of mycobacterial antibodies after BCG immunization; Impaired endothelial response and increased atherosclerosis due to BCG immunization; Mediation by immune response against mycobacterial and vascular HSP.

The article discusses the need to improve patient care through discriminate use of intracytoplasmic sperm injection (ICSI) and improved understanding of spermatozoa and oocyte. Topics discussed include treatment of infertility by ICSI, risks and disadvantages of ICSI compared with conventional in vitro fertilization (IVF), and randomized controlled trial of ICSI versus conventional IVF.

We have previously shown that antibody titres to several heat-shock proteins (Hsps) are elevated in dyslipidaemic patients and subjects with established vascular disease. Obesity is known to be associated with raised serum inflammatory markers suggesting a state of heightened immune activation. Hence, we have investigated the association between indices of obesity and several Hsp antibody titres in healthy subjects. Subjects (n=170) were recruited from among employees at the University of Surrey and the Royal Surrey County Hospital, Guildford, UK. Of these subjects, 35 were obese with a body mass index (BMI)30 kg/m2 (19 male and 16 female subjects), 58 were overweight with 30>BMI25 kg/m2 (36 male and 22 female subjects) and 77 were of a normal weight with BMI<25 kg/m2 (31 male and 46 female subjects). Overall, obese subjects had significantly higher plasma anti-Hsp-60 (P<0.001), anti-Hsp-65 (P<0.05) and anti-Hsp-70 (P<0.05) compared with overweight and normal weight subjects.International Journal of Obesity (2007) 31, 197–200. doi:10.1038/sj.ijo.0803385; published online 16 May 2006 [ABSTRACT FROM AUTHOR]

Idiopathic male infertility is often associated with genetic and epigenetic abnormalities. Such abnormalities include chromosome translocations and aneuploidies, Y chromosome microdeletions, and mutations of the CFTR gene. The unraveling of the human genome and ongoing animal transgenic studies have identified numerous other genes likely to be associated with male infertility. Initial reports from human studies have identified several candidate genes, including the protamine genes, SPO11, EIF5A2, USP26, ACT, and others. In addition to gene mutations and polymorphisms, damage to the chromatin resulting in single and double strand DNA breaks affects fertility. Recent studies are highlighting the role of such abnormalities in male infertility, and point to protamine defects as one cause of DNA damage. Epigenetic abnormalities also are being investigated, including the role of residual sperm mRNA in embryogenesis, and the effects of abnormal spermatogenesis on gene imprinting. These studies are pointing to complex etiologies and clinical ramifications in many infertile men. [ABSTRACT FROM AUTHOR]

Mechanical ventilation is an important tool for supporting critically ill patients but may also exert pathological forces on lung cells leading to Ventilator-Induced Lung Injury (VILI). We hypothesised that inhibition of the force-sensitive transient receptor potential vanilloid (TRPV4) ion channel may attenuate the negative effects of mechanical ventilation. Mechanical stretch increased intracellular Ca2+ influx and induced release of pro-inflammatory cytokines in lung epithelial cells that was partially blocked by about 30% with the selective TRPV4 inhibitor GSK2193874, but nearly completely blocked with the pan-calcium channel blocker ruthenium red, suggesting the involvement of more than one calcium channel in the response to mechanical stress. Mechanical stretch also induced the release of pro-inflammatory cytokines from M1 macrophages, but in contrast this was entirely dependent upon TRPV4. In a murine ventilation model, TRPV4 inhibition attenuated both pulmonary barrier permeability increase and pro-inflammatory cytokines release due to high tidal volume ventilation. Taken together, these data suggest TRPV4 inhibitors may have utility as a prophylactic pharmacological treatment to improve the negative pathological stretch-response of lung cells during ventilation and potentially support patients receiving mechanical ventilation. [ABSTRACT FROM AUTHOR]

Background Spleen tyrosine kinase (Syk) is an intracellular nonreceptor tyrosine kinase, which has been implicated as central immune modulator promoting allergic airway inflammation. Syk inhibition has been proposed as a new therapeutic approach in asthma. However, the direct effects of Syk inhibition on airway constriction independent of allergen sensitization remain elusive. Methods Spectral confocal microscopy of human and murine lung tissue was performed to localize Syk expression. The effects of prophylactic or therapeutic Syk inhibition on allergic airway inflammation, hyperresponsiveness, and airway remodeling were analyzed in allergen-sensitized and airway-challenged mice. The effects of Syk inhibitors BAY 61-3606 or BI 1002494 on airway function were investigated in isolated lungs of wild-type, PKCα-deficient, mast cell-deficient, or eNOS-deficient mice. Results Spleen tyrosine kinase expression was found in human and murine airway smooth muscle cells. Syk inhibition reduced allergic airway inflammation, airway hyperresponsiveness, and pulmonary collagen deposition. In naïve mice, Syk inhibition diminished airway responsiveness independently of mast cells, or PKCα or eNOS expression and rapidly reversed established bronchoconstriction independently of NO. Simultaneous inhibition of Syk and PKC revealed additive dilatory effects, whereas combined inhibition of Syk and rho kinase or Syk and p38 MAPK did not cause additive bronchodilation. Conclusions Spleen tyrosine kinase inhibition directly attenuates airway smooth muscle cell contraction independent of its protective immunomodulatory effects on allergic airway inflammation, hyperresponsiveness, and airway remodeling. Syk mediates bronchoconstriction in a NO-independent manner, presumably via rho kinase and p38 MAPK, and Syk inhibition might present a promising therapeutic approach in chronic asthma as well as acute asthma attacks. [ABSTRACT FROM AUTHOR]

Endothelial cell dysfunction is associated with cardiovascular disease and vasculogenic erectile dysfunction (ED). Measured via peripheral artery tonometry (PAT), endothelial dysfunction in the penis is an independent predictor of future cardiovascular events. The aim of the study was to determine whether measurement of endothelial dysfunction differentiates men with vasculogenic ED identified by duplex ultrasound from those without. A total of 142 men were retrospectively assessed using patient history, penile duplex ultrasonography (US) and PAT (EndoPAT 2000). ED was self-reported and identified on history. Vasculogenic ED was identified in men who exhibited a peak systolic velocity (PSV) of ⩽25 cm s−1 at 15 min following vasodilator injection. The reactive hyperemia index (RHI), a measurement of endothelial dysfunction in medium/small arteries, and the augmentation index (AI), a measurement of arterial stiffness, were recorded via PAT. Penile duplex US was used to categorize men into those with ED (n=111) and those without ED (n=31). The cohort with ED had a PSV of 21±1 cm s−1 (left cavernous artery) and 22±1 cm s−1 (right cavernous artery). The control group without ED had values of 39±2 cm s−1 (left) and 39±2 cm s−1 (right). Given the potential for altered endothelial function in diabetes mellitus, we confirmed that hemoglobin A1c, urinary microalbumin and vibration pulse threshold were not different in men with vasculogenic ED and those without. RHI in patients with ED (1.85±0.06) was significantly decreased compared to controls (2.15±0.2) (P<0.05). The AI was unchanged when examined in isolation, and when standardized to heart rate. Measurement of endothelial function with EndoPAT differentiates men with vasculogenic ED from those without. RHI could be used as a non-invasive surrogate in the assessment of vasculogenic ED and to identify those patients with higher cardiovascular risk. [ABSTRACT FROM AUTHOR]

Recent data suggest an increased risk of cardiovascular events and mortality in men on testosterone therapy (TT). To date, there are no long-term, prospective studies to determine safety. In such cases, retrospective observational studies can be helpful. We examined our patient database to determine whether TT altered the risk of all-cause mortality in men. We queried our hormone database for all men with a serum testosterone level and then examined charts to determine testosterone status. In all, 509 men had charts available for review. We linked our patient records to the National Death Index to determine mortality. Of the 509 men who met inclusion criteria, 284 were on TT and 225 did not use testosterone. Age (mean 54 years) and follow-up time (mean 10 years) were similar for both groups. In all, 19 men died-10 (4.4%) men not on TT and 9 (3.2%) men on TT. After adjusting for age and year of evaluation, there was no significant difference in the risk of death based on TT (hazard ratio 0.92, 95% confidence interval 0.36-2.35, P=1.0). There appears to be no change in mortality risk overall for men utilizing long-term testosterone therapy. [ABSTRACT FROM AUTHOR]