Prostasomes--their effects on human male reproduction and fertility

The prostate is a glandular male accessory sex organ vital fornormal fertility. It provides the prostatic component of seminalplasma which nourishes and protects sperm following ejaculation.Prostasomes are small (40–500 nm) membrane-bound vesiclesproduced by epithelial cells lining the prostate acini and area component of prostatic secretions. Although the existenceof these particles has been known for many years, their fullfunction and relevance to reproductive health are largely unknown.Proteomic studies have shown a wide range of proteins (enzymes,structural proteins and novel, unannotated proteins) presentin or on the surface of prostasomes providing them with a diversenature. Interestingly prostasomes are able to fuse with sperm,this event and the associated transfer of proteins lies at theheart of many of their proposed functions. Sperm motility isincreased by the presence of prostasomes and their fusion preventspremature acrosome reactions. Prostasomes have been shown toaid protection of sperm within the female reproductive tractbecause of immunosuppressive, antioxidant and antibacterialproperties. Clinically these functions imply a role for prostasomesin male factor infertility. However, the very functions thatpromote fertility may have negative connotations in later life;recent work has suggested that prostasomes are involved in prostatecancer. Clearly more work is needed to clarify the role of thesenovel particles and their impact on men’s health.     

Environmental procarcinogen hypothesis of bladder cancer in humans: Dapsone hydroxylation as a susceptibility risk factor for aggressive bladder cancer

The dapsone recovery ratio (DPRR), which is determined after single oral dose administration of dapsone by measuring the parent drug and hydroxylated metabolite, provides an in vivo measure of the efficiency of the drug metabolizing enzymes responsible for this metabolic route, putatively CYP3A4. This affords the potential to evaluate the hypothesis that this drug metabolizing enzyme system is involved in the pathogenesis of human bladder cancer. The present study is a matched case-control comparison of DPRR in patients with nonaggressive bladder cancer (grades I and II or Ta, T1 and T2, n = 43), patients with aggressive bladder cancer without invasion (grade III or Ta, T1 and T2, n = 32), patients with aggressive bladder cancer and invasion (grade III or T3 and T4, n = 32), and age- and gender-matched subjects with no urologic tumor on cystoscopy from an urban U.K. community (n = 85). Demographic variables associated with aggressive bladder cancer (Gill or T3, T4, Tis) included pack-years of smoking, alcohol intake, and occupational exposure; for nonaggressive bladder cancer variables included smoking and occupational exposure. DPRR exhibited an unimodal distribution in all subjects: activity was significantly reduced in both noninvasive and invasive aggressive bladder cancer, and was a significant risk factor for cancer after adjustment for other significant risk factors. Combining the two aggressive groups, the lowest tertile of DPRR activity was associated with a sixfold increase in risk (p < 0.02) compared with the upper tertile. We conclude that a low dapsone recovery ratio is an independent risk factor for aggressive bladder cancer irrespective of its stage of invasion and suggest that the enzymes involved in its metabolism are detoxifying enzymes for unknown environmental factors to which an urban community is exposed.     

Canadian Nationwide Survey on Pediatric Malnutrition Management in Tertiary Hospitals

Background: Disease-associated malnutrition (DAM) is common in hospitalized children. This survey aimed to assess current in-hospital practices for clinical care of pediatric DAM in Canada. Methods: An electronic survey was sent to all 15 tertiary pediatric hospitals in Canada and addressed all pillars of malnutrition care: screening, assessment, treatment, monitoring and follow-up. Results: Responses of 120 health care professionals were used from all 15 hospitals; 57.5% were medical doctors (MDs), 26.7% registered dietitians (RDs) and 15.8% nurses (RNs). An overarching protocol for prevention, detection and intervention of pediatric malnutrition was present or “a work in progress”, according to 9.6% of respondents. Routine nutritional screening on admission was sometimes or always performed, according to 58.8%, although the modality differed among hospitals and profession. For children with poor nutritional status, lack of nutritional follow-up after discharge was reported by 48.5%. Conclusions: The presence of a standardized protocol for the clinical assessment and management of DAM is uncommon in pediatric tertiary care hospitals in Canada. Routine nutritional screening upon admission has not been widely adopted. Moreover, ongoing nutritional care of malnourished children after discharge seems cumbersome. These findings call for the adoption and implementation of a uniform clinical care pathway for malnutrition among pediatric hospitals.     

Muscle weakness in a girl with autoimmune hepatitis and Graves' disease

Autoimmune hepatitis (AIH) is a chronic hepatic autoimmune disease of unknown etiology associated with inflammatory changes and autoantibodies. The combination of AIH, Grave’s disease, and myasthenia gravis (MG) is rare, with only one other case reported. We report a pediatric patient with AIH type 2 and Grave’s disease who developed MG whilst on a treatment with corticosteroids. A 13-year-old girl, diagnosed with thyrotoxicosis, was identified as having AIH type 2. During the course of her therapy, she developed muscle weakness. Investigations revealed increased anti-acetylcholine receptor (AChR) antibodies and her electromyopgraphy (EMG) was characteristic for MG. Her course is described here. This case highlights the importance of investigating muscle weakness in severely ill hospitalized patients. Support: none.     

The Case for Resource Sensitivity: Why It Is Ethical to Provide Cheaper,Less Effective Treatments in Global Health

When Dr. Hortense screens her patients in Chicago for cervical dysplasia and cancer, she conducts a pelvic exam, takes a sample of cervical cells, and sends them for Pap cytology and human papilloma virus DNA co‐testing. But when she conducts cervical cancer screening in Botswana, she employs a much simpler diagnostic strategy. She applies acetic acid to highlight precancerous lesions and visually inspects the cervix—a technique known as the VIA (visual inspection with acetic acid) method. She treats suspicious lesions with cryotherapy. There are multiple reasons that Dr. Hortense uses VIA in developing countries. It requires no specialized laboratory facilities or highly trained personnel. With immediate results, there is no delay in diagnosis and treatment, ensuring that patients are not lost to follow‐up. Most importantly, VIA is considerably cheaper than Pap and HPV co‐testing. This difference in care between Chicago and Botswana presents an ethical dilemma in global health: is it ethically acceptable to provide some patients cheaper treatments that are less effective or more toxic than the treatments other patients receive? We argue that it is ethical to consider local resource constraints when deciding what interventions to provide. The provision of cheaper, less effective health care is frequently the most effective way of promoting health and realizing the ethical values of utility, equality, and priority to the worst off.      

Uretric obstruction in Gardener's syndrome.

Desmoid tumours in Gardener's syndrome are a rare cause of ureteric obstruction. We report two cases of ureteric obstruction caused by desmoids, in a mother and daughter.