Prospects for clinically relevant epigenetic tests in the andrology laboratory

The review published by K1aver and Gromoll is a timely reminder of the ever-changing landscape of the clinical andrology laboratory as well as the limitations of current approaches to properly diagnose and treat male infertility. In a variety of disciplines, the clinical relevance of epigenetic status is becoming increasingly apparent. In this paper, the authors review the various studies that have evaluated the epigenetics （primarily DNA methylation） of sperm in the context of infertility, and they discuss the potential value of sperm epigenetic analysis in the workup of idiopathic male infertility.     

Gross efficiency of muscular work during step exercise at -15°C and 21 °C

In an effort to assess the effect of ambient temperature on the gross efficiency (Eff_g) of step exercise 12 subjects performed a modified step test either at —15 °C or 21°C ascending to three different heights (corresponding to light, moderate and heavy work), for 20 min each with a frequency of 18 steps min^-1. Heart rate (HR), rectal temperature, skin temperatures and heat flux from skin were continuously measured. Oxygen consumption was measured during the last 5 min of each step height and perceptions of thermal sensation were recorded. The results indicate that, while using conventional clothing adequate in these temperatures, Eff_g is altered in a contradictory manner. At —15°C Eff_g increased with increasing work load, whereas at 21°C it decreased when the work load increased. The highest Eff_g (heavy work at —15°C and light work at 21°C) values are reflected as rather similar rectal temperatures (37.4–37.7°C) and identical mean skin temperatures (32.8 °C) as well as the same (slightly warm) thermal sensation of the legs. At — 15 °C the lowest Eff_g in light work was probably hue to the need to warm up the muscles. At 21°C, on the contrary, the activation of heat dissipation systems was probably responsible for the lowest Eff_g in heavy work.     

Anti-angiogenic factors and pre-eclampsia in type 1 diabetic women

Aims/hypothesis  Elevated anti-angiogenic factors such as soluble fms-like tyrosine kinase 1 (sFlt1), a soluble form of vascular endothelial growth factor receptor, and endoglin, a co-receptor for TGFβ1, confer high risk of pre-eclampsia in healthy pregnant women. In this multicentre prospective study, we determined levels of these and related factors in pregnant women with type 1 diabetes, a condition associated with a fourfold increase in pre-eclampsia. Methods  Maternal serum sFlt1, endoglin, placental growth factor (PlGF) and pigment epithelial derived factor were measured in 151 type 1 diabetic and 24 healthy non-diabetic women at each trimester and at term. Results  Approximately 22% of the diabetic women developed pre-eclampsia, primarily after their third trimester visit. In women with pre-eclampsia (diabetic pre-eclampsia, n = 26) vs those without hypertensive complications (diabetic normotensive, n = 95), significant changes in angiogenic factors were observed, predominantly in the early third trimester and prior to clinical manifestation of pre-eclampsia. Serum sFlt1 levels were increased approximately twofold in type 1 diabetic pre-eclampsia vs type 1 diabetic normotensive women at the third trimester visit (p < 0.05) and the normal rise of PlGF during pregnancy was blunted (p < 0.05). Among type 1 diabetic women, third trimester sFlt1 and PlGF were inversely related (r² = 42%, p < 0.0001). Endoglin levels were increased significantly in the diabetic group as a whole vs the non-diabetic group (p < 0.0001). Conclusions/interpretation  Higher sFlt1 levels, a blunted PlGF rise and an elevated sFlt1/PlGF ratio are predictive of pre-eclampsia in pregnant women with type 1 diabetes. Elevated endoglin levels in women with type 1 diabetes may confer a predisposition to pre-eclampsia and may contribute to the high incidence of pre-eclampsia in this patient group.     

Fibronectin in synovial fluid and tissue in rheumatoid arthritis

Fibronectin is a glycoprotein found in body fluids, loose connective tissue matrix and in basement membranes. Fibronectin in rheumatoid arthritis synovial fluid was immunologically indistinguishable from the plasma form, as shown by double-diffusion analysis. Fibronectin isolated from rheumatoid synovial fluid by affinity chromatography on gelatin--Sepharose had a polypeptide pattern similar to that of plasma fibronectin in SDS--polyacrylamide gel electrophoresis. In fifty-one patients with rheumatoid arthritis and related diseases fibronectin concentrations is synovial fluid were 445 +/- 103 micrograms/ml (mean +/- SD) and within normal range, 335 +/- 52 micrograms/ml, in plasma. Immunofluorescence staining showed a prominent increase of fibronectin in the proliferating synovial connective tissue in rheumatoid arthritis as compared to normal synovial membrane. The results suggest an increased local production of fibronectin in rheumatoid synovial tissue.     

High‐frequency ventilation with the Dräger Babylog 8000plus: measuring the delivered frequency

Background: Ventilator frequency is one of the determinants of tidal volume delivery during high‐frequency ventilation. Clinicians increasingly use data on ventilator displays to inform their decisions. Aim: To measure the frequencies delivered by the Dräger Babylog 8000plus ventilator when used in high‐frequency mode. Methods: Ventilator waveforms using a test lung were recorded at the full range of settings 5–20 Hz using Spectra software at 1000 Hz. The changes in frequency produced by a 1‐ Hz change in set frequency were calculated. Actual and displayed frequencies were compared. Results: For settings up to 12 Hz, median (range) difference between set and delivered frequencies was 0 (?0.4 to +0.1) Hz. Above 12 Hz, delivered frequency varied by ?0.3 (?1.9 to +0.3) Hz. For 1‐ Hz changes in frequency settings, in the range 5–12 Hz, 1‐ Hz changes produced a change in delivered frequency of 1.0 (0.6–1.4) Hz. Above 12 Hz, the corresponding changes were 0.7 (0–2.9) Hz. The ventilator displays the set frequency during operation rather than the delivered frequency. Conclusion: At 12 Hz and below, the differences between set and delivered frequencies were relatively small compared with those at 13 Hz and higher. Above 13 Hz, the difference between set and delivered frequencies was up to 2.9 Hz. Some frequency setting changes did not result in a change in delivered frequency.     

Density of γ/δ+ T cells in the jejunal epithelium of patients with coeliac disease and dermatitis herpetiformis is increased with age

Increased density of γ/δ T cell receptor (TCR)⁺ intraepithelial lymphocytes is the only characteristic in the jejunum of patients with coeliac disease and dermatitis herpetiformis which is not normalized on a gluten-free diet. We explored the age-dependent changes in intraepithelial γ/δ and α/β TCR⁺ cells from 137 biopsies from patients with coeliac disease and dermatitis herpetiformis and from controls. Biopsy specimens from 100 patients with coeliac disease and dermatitis herpetiformis and from 37 controls were studied with an immunohistochemical method using MoAbs to T cell receptors and peroxidase staining. An increase in the density of intraepithelial γ/δ T cells above the mean +2 s.d. of the density in controls was present in 97 of 100 specimens from patients with coeliac disease and dermatitis herpetiformis. The density of γ/δ⁺ cells of patients with coeliac disease and dermatitis herpetiformis on a normal gluten-containing diet showed a positive correlation with age (r = 0.45, P< 0.0001). In controls, the density of γ/δ⁺ cells remained low throughout the age-range studies, from age 0.6–57 years. In controls, α/β⁺ cells increased with age (r = 0.57, P< 0.001). The increase in density of intraepithelial lymphocytes with age is in agreement with their thymus-independent character and local proliferation.     

Adenosine triphosphate treatment for meconium aspiration-induced pulmonary hypertension in pigs

To investigate the pulmonary haemodynamic effects of meconium aspiration and subsequent adenosine triphosphate (ATP) treatment, 12 anaesthetized and ventilated pigs (wt 24-28 kg) received either ATP or an equal volume of saline into the right heart in doses of 0.02 to 0.80 lmol kg^-1 min^?1 after intratracheal administration of 2 mL kg^?1 of human meconium. Meconium instillation induced significant increases in pulmonary vascular pressures and total and postarterial resistances calculated from pulmonary artery occlusion studies, but did not affect the systemic haemodynamics, except for a fall in heart rate and increase in central venous pressure. Infusion of ATP at the lowest doses (0.02 and 0.08 µmol kg^?1 min^?1) selectively decreased the pulmonary arterial pressure and vascular resistance and at 0.32 and 0.80 µmol kg^?1 min^?1 reduced both the pulmonary and systemic resistances. In the lung circulation the increasing doses of ATP reduced preferably the arterial, but also the postarterial resistance. Withdrawal of ATP infusion led to a significant rebound effect especially in the postarterial segment of the lung circulation. Meconium aspiration thus induces an acute, predominantly postarterial obstruction in the lung circulation and infusion of ATP at low doses selectively dilates the pulmonary vascular bed and may help to preclude elevation of capillary pressures in meconium aspiration-induced pulmonary hypertension.     

Detection of a de novo interstitial 2q microdeletion by CGH microarray analysis in a patient with limb malformations, microcephaly and mental retardation

We describe the cytogenetic diagnosis using BAC- and oligonucleotide microarrays of a 16-year-old Laotian-American female, who first presented at 2 1/2 years of age with microcephaly, developmental retardation, and skeletal abnormalities of the upper limb including mild syndactyly of the second and third and the third and fourth fingers, short middle phalanges and clinodactyly of the fifth digit at the distal interphalangel joint on both hands, and symphalangism of the metacarpal-phalangeal joints of the second and fifth digits bilaterally. Her lower limbs displayed symphalangism of the metatarsal-phalangeal joint of the second, third, and fourth digits on both feet, with fusion of the middle and distal phalanges of the second and fifth digits and hallux valgus bilaterally. G-banded chromosomal study at age 4 was normal. However, comparative genomic hybridization at age 15 with the Spectral Genomics 1 Mb Hu BAC array platform indicated a microdeletion involving two BAC clones, RP11-451F14 --> RP11-12N7 at 2q31.1. The maximal deletion on initial analysis comprised the HOXD cluster, which is implicated in limb development. Fluorescence in situ hybridization (FISH) using the RP11-451F14 probe confirmed the deletion. Both parents were negative for the deletion. Additional FISH using BAC RP11-387A1, covering the HOXD cluster, limited the maximal deletion to approximately 2.518 Mb, and excluded involvement of the HOXD cluster. The Agilent 44K and 244K platforms demonstrated a deletion of approximately 2,011,000 bp, which did not include the HOXD cluster. The malformations in our patient may be caused by deletion of a regulatory element far upstream of the HOXD cluster.     

Women's experiences with vaginal pessary use

Title.  Women's experiences with vaginal pessary use.
Aim.  This paper is a report of a study of the lived experiences of women using vaginal pessaries for the treatment of urinary incontinence (UI) and/or pelvic organ prolapse.
Background.  The use of a vaginal pessary offers a non-surgical treatment option to provide physical support to the bladder and internal organs. As the literature asserts, a woman's choice to use a pessary is very individual and involves not only physical, but also psychological and emotional considerations.
Method.  Narrative inquiry was used to conduct face-to-face semi-structured interviews in 2007 with 11 postmenopausal women who accessed services from a Urogynecology Clinic in Eastern Canada.
Findings.  The women's stories revealed that living with a pessary is a life-changing experience and an ongoing learning process. The women's comfort level and confidence in caring for the device figured prominently in their experiences. Psychosocial support provided by the clinic nurses also played a primary role in the women's experiences.
Conclusion.  Women and healthcare professionals need to be aware of the personal isolation and embarrassment, and social and cultural implications that urinary incontinence may cause as well as the subjective experiences of using a pessary. With appropriate support, vaginal pessaries can provide women with the freedom to lead active, engaged and social lives.