Acetylcysteine for prevention of acute deterioration of renal function following elective coronary angiography and intervention

Context The antioxidant acetylcysteine prevents acute contrast nephrotoxicity in patients with impaired renal function who undergo computed tomography scanning. However, its role in coronary angiography is unclear.

Objective To determine whether oral acetylcysteine prevents acute deterioration in renal function in patients with moderate renal insufficiency who undergo elective coronary angiography.

Design and Setting Prospective, randomized, double-blind, placebo-controlled trial conducted from May 2000 to December 2001 at the Grantham Hospital at the University of Hong Kong.

Participants Two hundred Chinese patients aged mean (SD) 68 (6.5) years with stable moderate renal insufficiency (creatinine clearance <60 mL/min [1.00 mL/s]) who were undergoing elective coronary angiography with or without intervention.

Intervention Participants were randomly assigned to receive oral acetylcysteine(600 mg twice per day; n = 102) or matching placebo tablets (n = 98) on the day before and the day of angiography. All patients received low-osmolality contrast agent.

Main Outcome Measures Occurrence of more than a 25% increase in serum creatinine level within 48 hours after contrast administration; change in creatinine clearance and serum creatinine level.

Results Twelve control patients (12%) and 4 acetylcysteine patients (4%) developed a more than 25% increase in serum creatinine level within 48 hours after contrast administration (relative risk, 0.32; 95% confidence interval [CI], 0.10-0.96; P = .03). Serum creatinine was lower in the acetylcysteine group (1.22 mg/dL [107.8 µmol/L]; 95% CI, 1.11-1.33 mg/dL vs 1.38 mg/dL [122.9 µmol/L]; 95% CI, 1.27-1.49 mg/dL; P = .006) during the first 48 hours after angiography. Acetylcysteine treatment significantly increased creatinine clearance from 44.8 mL/min (0.75 mL/s) (95% CI, 42.7-47.6 mL/min) to 58.9 mL/min (0.98 mL/s) (95% CI, 55.6-62.3 mL/min) 2 days after the contrast administration (P<.001).The increase was not significant in the control group (from 42.1 to 44.1 mL/min [0.70 to 0.74 mL/s]; P = .15). The benefit of acetylcysteine was consistent among various patient subgroups and persistent for at least 7 days. There were no major treatment-related adverse events.

Conclusion Acetylcysteine protects patients with moderate chronic renal insufficiency from contrast-induced deterioration in renal function after coronary angiographic procedures, with minimal adverse effects and at a low cost.

Replication of hepatitis B in HBsAg-positive siblings

Persistent hepatitis B virus (HBV) replication is important for progression of chronic liver diseases. To understand whether there is a trend of HBV replication in siblings or not, 1850 relatives of patients with hepatocellular carcinoma (HCC) were examined prospectively for liver function test, viral markers and HBV DNA. The prevalence of HBsAg in the parents', siblings', children's and grandchildren's generations were 43.4%, 57.2%, 35.5% and 32.1%, respectively. The prevalence of hepatitis B e antigen (HBeAg) in sibling's generation (mean age 44.4 years) was 19%, which is higher than that of asymptomatic HBsAg carriers. For siblings in the children's generation, the prevalence of HBeAg in hepatitis B surface antigen (HBsAg) carriers declined from 40% in the eldest siblings to 19% in the youngest siblings. In 75 families clustered with three or more HBsAg carrier siblings, the mean age for seven families of which all siblings remained HBeAg + was younger, whereas the mean age for 35 families of which all siblings had cleared HBeAg was older. For the remaining 33 families, in only 10 families had the older siblings cleared the HBeAg earlier than the younger siblings. Twenty families showed that younger siblings cleared the HBeAg earlier than the older or middle siblings. We concluded that HBV replication in HCC relatives cannot be explained by familial tendency alone. A significant number of younger siblings appeared to have a shorter HBV replication phase than their older siblings. The possible role of this in maternal–fetal transmission is discussed.

Psychological and interpersonal dimensions of sexual function and dysfunction.

To highlight the salient psychological and interpersonal issues contributing to sexual health and dysfunction; to offer a four-tiered paradigm for understanding the evolution and maintenance of sexual symptoms; and to offer recommendations for clinical management and research.

Conceptualizing women's sexual function : linear vs. circular models of sexual response

Introduction. The lack of an adequate empirical base for models of female sexual response is a critical issue within the female sexual dysfunction (FSD) literature.

Aim. The current research compared the extent to which a linear model of sexual response and Basson's circular model of female sexual response represent the sexual function of women with and without FSD.

Main Outcome Measures. Women's levels of sexual function/dysfunction were assessed with the Female Sexual Function Index and additional items measured women's endorsement of models of female sexual function as representing their own sexual experience.

Methods. An anonymous online survey assessing female sexual response and associated aetiological factors was completed by a random sample of 404 women.

Results. Although the linear model of sexual response was a good fit for women with and without sexual dysfunction, the relationship between sexual arousal and orgasm was mediated by sexual desire for women with FSD. The fit of the initial circular model of women's sexual response was poor for both groups. Following pathway modification, the modified circular model adequately represented the responses of both groups and revealed that a number of the relationships between sexual response variables were stronger for women with FSD.

Conclusions. The linear model was a more accurate representation of sexual response for women with normal sexual function than women with FSD and sexual arousal and orgasm was mediated by sexual desire for women with FSD. The modified circular model was a more accurate representation of the sexual response of women with FSD than women with normal sexual function.

Improved endothelial function following a 14 month resistance exercise training program in adults with type 2 diabetes

Objective
We examined the effect of a 14-month progressive resistance training (PRT) program on endothelial function in both a supervised training (Center) group and non-supervised training (Home) group of patients with type 2 diabetes. We studied 28 men and women with type 2 diabetes who participated in a 14-month PRT involving an initial 2-month supervised program and a 12-month maintenance program.

Methods
Endothelial function testing was performed through laser doppler flow responses in the skin microcirculation to iontophoresis of acetylcholine (ACh) and sodium nitroprusside (NaNP) and doses of 4, 8 and 16 mC were used. Measurements of vascular response (VR), HbA1c, weight and blood pressure were performed at 0, 2 and 14 months.

Results
VR to ACh and NaNP was significantly increased at 14 months compared with baseline in both the Center and Home groups. However, no between-group differences were observed. A significant correlation was observed between HbA1c and VR to ACh at baseline and 8 weeks using 8 mC dose of ACh. There was a strong correlation between HbA1c at baseline and VR at 14 months using all three doses of ACh (4 mC:r = −0.546, p = 0.003, 8 mC:r = −0.470, p = 0.002, 16 mC:r = −0.547, p = 0.006).

Conclusions/interpretation
Endothelial function is improved following 14 months of PRT in type 2 diabetes both in a supervised and non-supervised program. Strong correlations with HbA1c including initial HbA1c levels suggest that glycemic control may be an important factor in long-term regulation of endothelial function.

Funding special education provision by means of discriminant function analysis

This thesis is concerned with the development of a funding mechanism, the Student Resource Index, which has been designed to resolve a number of difficulties which emerged following the introduction of integration or inclusion as an alternative means of providing educational support to students with disabilities in the Australian State of Victoria. Prior to 1984, the year in which the major integration or inclusion initiatives were introduced, the great majority of students with disabilities were educated in segregated special schools, however, by 1992 the integration initiatives had been successful in including within regular classes approximately half of the students in receipt of additional educational assistance on the basis of disability. The success of the integration program brought with it a number of administrative and financial problems which were the subject of three government enquiries. Central to these difficulties was the development of a dual system of special education provision. On one hand, additional resources were provided for the students attending segregated special schools by means of weighted student ratios, with one teacher being provided for each six students attending a special school. On the other hand, the requirements of individual students integrated into regular schools were assessed by school-based committees on the basis of their perceived extra educational needs. The major criticism of this dual system of special education funding was that it created inequities in the distribution of resources both between the systems and also within the systems. For example, three students with equivalent needs, one of whom attended a special school and two of whom attended different regular schools could each be funded at substantially differing levels. The solution to these inequities of funding was seen to be in the development of a needs based funding device which encompassed all students in receipt of additional disability related educational support. The Student Resource Index developed in this thesis is a set of behavioural descriptors designed to assess degree of additional educational need across a number of disability domains. These domains include hearing, vision, communication, health, co-ordination (manual and mobility), intellectual capacity and behaviour. The completed Student Resource Index provides a profile of the students’ needs across all of these domains and as such addresses the multiple nature of many disabling conditions. The Student Resource Index was validated in terms of its capacity to predict the ‘known’ membership or the type of special school which some 1200 students in the sample currently attended. The decision to use the existing special school populations as the criterion against which the Student Resource Index was validated was based on the premise that the differing resource levels of these schools had been historically determined by expert opinion, industrial negotiation and reference to other special education systems as the most reliable estimate of the enrolled students’ needs. When discriminant function analysis was applied to some 178 students attending one school for students with mild intellectual disability and one facility for students with moderate to severe intellectual disability the Student Resource Index was successful in predicting the student's known school in 92 percent of cases. An analysis of those students (8 percent) which the Student Resource Index had failed to predict their known school enrolment revealed that 13 students had, for a variety of reasons, been inappropriately placed in these settings. When these students were removed from the sample the predictive accuracy of the Student Resource Index was raised to 96 percent of the sample. By comparison the domains of the Vineland Adaptive Behaviour Scale accurately predicted known enrolments of 76 percent of the sample. By way of replication discriminant function analysis was then applied to the Student Resource Index profiles of 518 students attending Day Special Schools (Mild Intellectual Disability) and 287 students attending Special Developmental Schools (Moderate to Severe Intellectual Disability). In this case, the Student Resource Index profiles were successful in predicting the known enrolments of 85 percent of students. When a third group was added, 147 students attending Day Special Schools for students with physical disabilities, the Student Resource Index predicted known enrolments in 80 percent of cases. The addition of a fourth group of 116 students attending Day Special Schools (Hearing Impaired) to the discriminant analysis led to a small reduction in predictive accuracy from 80 percent to 78 percent of the sample. A final analysis which included students attending a School for the Deaf-Blind, a Hospital School and a Social and Behavioural Unit was successful in predicting known enrolments in 71 percent of the 1114 students in the sample. For reasons which are expanded upon within the thesis it was concluded that the Student Resource Index when used in conjunction with discriminant function analysis was capable of isolating four distinct groups on the basis of their additional educational needs. If the historically determined and varied funding levels provided to these groups, inherent in the cash equivalent of the staffing ratios of Day Special Schools (Mild Intellectual Disability), Special Development Schools (Moderate to Severe Intellectual Disability), Day Special Schools (Physical Disability) and Day Special Schools (Hearing Impairment) are accepted as reasonable reflections of these students’ needs these funding levels can be translated into funding bands. These funding bands can then be applied to students in segregated or inclusive placements. The thesis demonstrates that a new applicant for funding can be introduced into the existing data base and by the use of discriminant function analysis be allocated to one of the four groups. The analysis is in effect saying that this new student’s profile of educational needs has more in common with Group A than with the members of Groups B, C, or D. The student would then be funded at Group A level. It is immaterial from a funding point of view whether the student decides to attend a segregated or inclusive setting. The thesis then examines the impact of the introduction of Student Resource Index based funding upon the current funding of the special schools in one of the major metropolitan regions. Overall, such an initiative would lead to a reduction of 1.54 percent of the total funding accruing to the region’s special schools.

A critical analysis of the independence of the internal audit function : evidence from Australia

Purpose – This study aims to critically analyse the independence of the internal audit function through its relationship with management and the audit committee.

Design/methodology/approach – Results are based on a critical comparison of responses from questionnaires sent out to Australian chief audit executives (CAEs) versus existing literature and best practice guidelines.

Findings – With respect to the internal audit function's relationship with management, threats identified include: using the internal audit function as a stepping stone to other positions; having the chief executive officer (CEO) or chief finance officer (CFO) approve the internal audit function's budget and provide input for the internal audit plan; and considering the internal auditor to be a “partner”, especially when combined with other indirect threats. With respect to the relationship with the audit committee, significant threats identified include CAEs not reporting functionally to the audit committee; the audit committee not having sole responsibility for appointing, dismissing and evaluating the CAE; and not having all audit committee members or at least one member qualified in accounting.

Originality/value – This study introduces independence threat scores, thereby generating analysis of the internal audit function's independence taking into account a combination of threats.

The effects of treating male hypogonadism on couples' sexual desire and function

Introduction: Hypogonadism is a common endocrine condition characterized by low levels of testosterone (T) and marked by numerous symptoms, one of which is low sexual desire. Studies comparing T delivery systems have suggested that hypogonadal men’s partners may be at risk from exposure to T gels. Little other mention is found of the impact of hypogonadism and its treatment on a man’s partner and the couple’s sexual function.

Aim: To assess sexual desire and sexual function in hypogonadal men and their woman partners before and after treatment with T replacement therapy.

Methods: Twenty-one hypogonadal men and 18 partners were recruited from a   tertiary endocrine clinic, and were compared with a control group of 20 eugonadal age-matched men and their partners. All men had baseline blood tests to confirm their status as hypogonadal or eugonadal, and hypogonadal men repeated tests at 3-month intervals. All participants completed the Sexual Desire Inventory (SDI) and sexual function questionnaires at baseline and at 3-month intervals until the hypogonadal men attained normal T levels.

Main Outcome Measures: Pre- and post-treatment SDI and sexual function questionnaires were compared once T normalization was achieved. Between- and within-group comparisons were carried out.

Results: Pretreatment hypogonadal men recorded lower levels of sexual desire and function than controls, but significantly improved once hypogonadism was corrected. Eugonadal controls recorded no significant changes in either sexual desire or function during the study. Partners of the hypogonadal men reported no changes on the SDI, but significant improvements in sexual function as their partners recovered.

Conclusion: SDI and sexual function measures reflect sexual changes that  accompany rising serum T levels during correction of male hypogonadism. Women partners reported more satisfaction, less pain, and improved sexual function following the men’s treatment. Treatments affecting one partner potentially have important effects on the other.

Natural history of hepatitis B in perinatally infected carriers

Objectives: To establish natural seroconversion rates and incidence of hepatic pathology in perinatally infected hepatitis B carriers.

Methods: Seventy three perinatally infected hepatitis B carriers identified through maternal screening were evaluated. Fifty three were born to parents from the Indian subcontinent, nine were Oriental, six were Afro-Caribbean, and five were white. Median follow up was 10.24 (range 2.02–20.16) years.

Results: Only three of the children followed up had cleared hepatitis B surface antigen during this period, and 30% of the children had seroconverted to anti-HBe. Seroconversions to anti-HBe were observed in Asian (18/50) and white (4/5) children, but not in Oriental or Afro-Caribbean children. More girls (40%) than boys (23%) had seroconverted, but the difference was not significant. All children were asymptomatic with normal physical examination, growth, and development. Almost half (48%) of the hepatitis B e antigen (HBeAg) positive children had normal hepatic transaminases and liver function. Thirty five liver biopsies were performed in children with active virus replication (HBeAg or hepatitis B virus DNA positive) who were being considered for antiviral treatment as part of a clinical trial and were scored using the Ishak method. Two thirds (62%) of the children had mild hepatitis, 60% had mild fibrosis, and 18% had moderate to severe fibrosis. There was a weak correlation between histological evidence of hepatitis and hepatic transaminase activity, implying that biochemical monitoring of hepatic disease activity may be ineffective.

Conclusions: These asymptomatic hepatitis B virus carrier children remain infectious in the medium to long term with notable liver pathology. They should receive antiviral treatment to reduce infectivity and to prevent further progression of liver disease. Hepatic transaminases alone are not a reliable marker of liver pathology, and liver histology is essential before consideration for antiviral treatment.

Influenza A virus-specific CD8.sup.+ T-cell responses : from induction to function

Seasonal influenza virus infection is a leading cause of illness and mortality in young children and the elderly each year. Current influenza vaccines generate protective antibody responses; however, these must be given annually to provide protection against serologically distinct viruses. By contrast, CD8.sup.+ T cells are capable of recognizing conserved antigenic determinants within the influenza virion and, as such, may provide protection against a number of variant strains of the virus. CD8.sup.+ T cells play a critical key role in controlling and resolving influenza virus infections via the production of cytokines and cytolytic mediators. This article focuses on the induction of the influenza-specific CD8.sup.+ T-cell response and how these cells acquire and maintain effector function after induction. Moreover, we discuss how cytotoxic T-lymphocyte function correlates with protection following vaccination.

Relationships between measures of fitness, physical activity, body composition and vascular function in children

Background : The prevalence of obesity and physical inactivity in Western countries has increased rapidly. Both are modifiable risk factors for cardiovascular disease. Atherosclerosis begins in childhood and endothelial dysfunction is its earliest detectable manifestation.

Methods : We assessed flow-mediated dilation (FMD) in 129 children (75 female; 10.3 + 0.3 yrs; 54 male; 10.4; 0.3 yrs). FMD was normalised for differences in the eliciting shear rate stimulus between subjects (SR_AUC). Fitness was assessed as peak oxygen uptake during an incremental treadmill exercise test (VO₂peak). Body composition was measured using a dual-energy X-ray absorptiometry (DEXA) scan. Physical activity (PA) was assessed using Actigraph accelerometers. The cohort was split into tertiles according to FMD% and also FMD% corrected for SR_AUC to gain insight into the determinants of vascular function.

Results : Across the cohort, significant correlations were observed between FMD%/SR_AUC and DEXA percentage fat (r = −0.23, p = 0.009) and percentage lean mass (r = 0.21, p = 0.008), and also with PA performed at moderate-to-high intensity (r = 0.363, p = 0.001). For children in the lowest FMD%/SR_AUC tertile, a stronger relationship with all PA measures was observed, particularly with high intensity PA (r = 0.572, P = 0.003). Regression analysis revealed that high intensity PA was the only predictor of impaired FMD%/SR_AUC.

Conclusions : These data suggest that traditional risk factors for CHD in adult populations impact upon vascular function in young people. Furthermore, it appears that individuals with impaired FMD may benefit from performing high intensity PA, whereas no relationships exist between FMD and lower intensities of PA or between PA and FMD in those subjects who possess preserved vascular function a priori.

Semantic and layered protein function prediction from PPI networks

Background The past few years have seen a rapid development in novel high-throughput technologies that have created large-scale data on protein-protein interactions (PPI) across human and most model species. This data is commonly represented as networks, with nodes representing proteins and edges representing the PPIs. A fundamental challenge to bioinformatics is how to interpret this wealth of data to elucidate the interaction of patterns and the biological characteristics of the proteins. One significant purpose of this interpretation is to predict unknown protein functions. Although many approaches have been proposed in recent years, the challenge still remains how to reasonably and precisely measure the functional similarities between proteins to improve the prediction effectiveness.

Results We used a Semantic and Layered Protein Function Prediction (SLPFP) framework to more effectively predict unknown protein functions at different functional levels. The framework relies on a new protein similarity measurement and a clustering-based protein function prediction algorithm. The new protein similarity measurement incorporates the topological structure of the PPI network, as well as the protein's semantic information in terms of known protein functions at different functional layers. Experiments on real PPI datasets were conducted to evaluate the effectiveness of the proposed framework in predicting unknown protein functions.

Conclusion The proposed framework has a higher prediction accuracy compared with other similar approaches. The prediction results are stable even for a large number of proteins. Furthermore, the framework is able to predict unknown functions at different functional layers within the Munich Information Center for Protein Sequence (MIPS) hierarchical functional scheme. The experimental results demonstrated that the new protein similarity measurement reflects more reasonably and precisely relationships between proteins.

Psychological and interpersonal dimensions of sexual function and dysfunction

Introduction. There are limited outcome data on the etiology and efficacy of psychological interventions for male and female sexual dysfunction as well as the role of innovative combined treatment paradigms.
Aim. This study aimed to highlight the salient psychological and interpersonal issues contributing to sexual health and dysfunction, to offer an etiological model for understanding the evolution and maintenance of sexual symptoms, and to offer recommendations for clinical management and research.
Methods. This study reviewed the current literature on the psychological and interpersonal issues contributing to male and female sexual dysfunction.
Main Outcome Measure. This study provides expert opinion based on a comprehensive review of the medical and psychological literature, widespread internal committee discussion, public presentation, and debate.
Results. Medical and psychological therapies for sexual dysfunctions should address the intricate biopsychosocial influences of the patient, the partner, and the couple. The biopsychosocial model provides an integrated paradigm for understanding and treating sexual dysfunction.
Conclusions. There is need for collaboration between healthcare practitioners from different disciplines in the evaluation, treatment, and education issues surrounding sexual dysfunction. In many cases, neither psychotherapy alone nor medical intervention alone is sufficient for the lasting resolution of sexual problems. The assessment of male, female, and couples’ sexual dysfunction should ideally include inquiry about predisposing, precipitating, maintaining, and contextual factors. Research is needed to identify efficacious combined and/or integrated treatments for sexual dysfunction.