Salivary Testosterone Levels and Health Status in Men and Women in the British General Population: Findings from the Third National Survey of Sexual Attitudes and Lifestyles (Natsal-3).

CONTEXT: Salivary T (Sal-T) measurement by liquid chromatography-tandem mass spectroscopy resents the opportunity to examine health correlates of Sal-T in a large-scale population survey. OBJECTIVE: This study sought to examine associations between Sal-T and health-related factors in men and women age 18-74 years. DESIGN AND SETTING: Morning saliva samples were obtained from participants in a cross-sectional probability-sample survey of the general British population (Natsal-3). Self-reported health and lifestyle questions were administered as part of a wider sexual health interview. PARTICIPANTS: Study participants included 1599 men and 2123 women. METHODS: Sal-T was measured using liquid chromatography-tandem mass spectroscopy. Linear regression was used to examine associations between health factors and mean Sal-T. RESULTS: In men, mean Sal-T was associated with a range of health factors after age adjustment, and showed a strong independent negative association with body mass index (BMI) in multivariable analysis. Men reporting cardiovascular disease or currently taking medication for depression had lower age-adjusted Sal-T, although there was no association with cardiovascular disease after adjustment for BMI. The decline in Sal-T with increasing age remained after adjustment for health-related factors. In women, Sal-T declined with increasing age; however, there were no age-independent associations with health-related factors or specific heath conditions with the exception of higher Sal-T in smokers. CONCLUSIONS: Sal-T levels were associated, independently of age, with a range of self-reported health markers, particularly BMI, in men but not women. The findings support the view that there is an age-related decline in Sal-T in men and women, which cannot be explained by an increase in ill health. Our results demonstrate the potential of Sal-T as a convenient measure of tissue androgen exposure for population research.

Combined preputial advancement and phallopexy as a revision technique for treating paraphimosis in a dog.

A 7-year-old neutered male Jack Russell terrier-cross was presented for signs of recurrent paraphimosis, despite previous surgical enlargement of the preputial ostium. Revision surgery was performed using a combination of preputial advancement and phallopexy, which resulted in complete and permanent coverage of the glans penis by the prepuce, and at 1 year postoperatively, no recurrence of paraphimosis had been observed. The combined techniques allow preservation of the normal penile anatomy, are relatively simple to perform and provide a cosmetic result. We recommend this combination for the treatment of paraphimosis in the dog, particularly when other techniques have failed.

Total knee replacement in a dog with a non-union type B3 tibial plateau fracture.

A six-year-old German Shorthaired Pointer was presented with a 12 month history of left pelvic limb lameness following trauma. Clinical examination revealed marked thickening and reduced range-of-motion of the left stifle and radiographs were suggestive of a non-union type B3 tibial plateau fracture with severe secondary osteoarthritis. Total knee replacement was performed with adjunctive stabilization of the proximal tibial fracture fragment. Clinical follow-up at six and 12 months with quantitative gait analysis revealed significant improvement in limb function.

A novel method for defining the Greyhound talocrural joint axis of rotation for hinged transarticular external skeletal fixation.

In order to apply hinged transarticular external skeletal fixation for stabilization of the injured canine tarsal joint, knowledge of the three-dimensional (3D) location and orientation of the transverse axis is necessary. This method of immobilization may be used as a primary or adjunctive method of stabilisation for a large number of traumatic conditions. Using pin-mounted markers in the cadaveric Greyhound crus and talus, a closed-form solution of absolute orientation was used to identify, on radiographs, the lateral and medial locations of the transverse axis by tracking the 3D excursions of the markers during flexion and extension. A line was drawn across the dorsal aspect of the calcaneus from the most dorsal point on the distal articular surface(proximal intertarsal joint: PIJ) to the most dorsal point on its proximal articulation with the body of the talus, and the location of the centre of rotation was expressed in terms of the length of that line. In seven Greyhound tarsal joints, the medial end of the axis was located 73 ± 10% proximal to the PIJ and 11 ± 7% dorsal to the line. The lateral end was 73 ± 9% proximal tothe PIJ and -2 ± 3% plantar to the line.

An ex vivo investigation of the effect of the TATE canine elbow arthroplasty system on kinematics of the elbow.

OBJECTIVE: To devise a kinematic technique to objectively ascertain the location and orientation of the centre of rotation of the canine elbow and to compare this axis following arthroplasty with the first generation TATE™ prosthesis in an ex vivo model. METHODS: Five pairs of cadaveric forelimbs were obtained and proximal limb soft tissues removed. Pin-mounted reflective markers were applied to the humerus and ulna. Limbs were mounted on a frame and six trials of the elbow manually cycled through its sagittal range of motion captured using 4 Qualisys cameras at 120 Hz. Radiography was performed to identify marker position. TATE™ cartridges were implanted and kinematic analysis repeated. Kinematic data were imported into custom software and the three-dimensional joint centre of rotation defined using a closed-form solution for absolute orientation. Paired t tests were performed to determine if the centre of rotation of the elbow differed significantly (P<0·05) pre- and postoperatively and between left and right limbs. RESULTS: There was no significant difference in three-dimensional orientation of the elbow axis between pre and postoperative measurements or between left and right limbs. CLINICAL SIGNIFICANCE: A critical factor in obtaining a successful functional outcome following elbow arthroplasty in humans is accurate reconstruction of the anatomic centre of rotation. The first generation TATE canine elbow arthroplasty cartridge and its instrumentation accurately reconstructed the anatomic centre of rotation in 8 of the 10 elbows assessed in this ex vivo model.

Ex vivo evaluation of the biomechanical effect of varying monocortical screw numbers on a plate-rod canine femoral gap model.

OBJECTIVE: To compare the biomechanical behaviour of plate-rod constructs with varying numbers of monocortical screws applied to an ex vivo canine femoral-gap ostectomy model. SAMPLE POPULATION: Twenty Greyhound dog cadaveric femurs. METHODS: Bone mineral density (BMD) was assessed with dual x-ray absorptiometry. Bones were assigned to four groups. Bones had a 12-hole 3.5 mm locking compression plate with one bicortical non-locking cortical screw in the most proximal and distal plate holes and an intramedullary Steinmann pin applied across a 20 mm mid-diaphyseal ostectomy. Additionally, one to four monocortical non-locking cortical screws were then placed (Groups 1-4 respectively) in the proximal and distal fragments. Stiffness and axial collapse were determined before and after cyclic axial loading (6000 cycles at 20%, 40%, and 60% of mean bodyweight [total: 18000 cycles]). Constructs subsequently underwent an additional 45000 cycles at 60% of bodyweight (total: 63000 cycles). Loading to failure was then performed and ultimate load and mode of failure recorded. RESULTS: The BMD did not differ significantly between groups. Construct stiffness for group 1 was significantly less than group 4 (p = 0.008). Stiffness showed a linear increase with an increasing number of monocortical screws (p = 0.001). All constructs survived fatigue loading. Load-to-failure was not significantly different between groups. Mean load- to-failure of all groups was >1350N. CLINICAL RELEVANCE: Ex vivo canine large-breed femurs showed adequate stability biomechanically and gradually increasing stiffness with increasing monocortical screw numbers.

The pedicled myocutaneous flap as a choice reconstructive technique for immediate adjuvant brachytherapy in sarcoma treatment.

Successful treatment of soft-tissue sarcomas is highly dependent on total tumour resection coupled with adjuvant radiation therapy to achieve local control and decrease recurrence. Reconstruction of soft-tissue defects after resection aims to cover vital structures, while providing enough stable tissue to withstand adjuvant brachytherapy treatment. In the present study, pedicled myocutaneous flaps were used as a vital adjunct in the treatment of soft-tissue sarcoma, and our experience with 2 such patients is described. The flaps served to reconstruct large three-dimensional defects while providing stable coverage over brachytherapy hardware to allow for delivery of radiation in the immediate postoperative period. Pedicled locoregional myocutaneous flaps provide a safe, easy, and reliable reconstructive technique in the treatment of soft-tissue sarcoma.

Modification of the cranial closing wedge ostectomy technique for the treatment of canine cruciate disease. Description and comparison with standard technique.

OBJECTIVE: To describe a modification of the cranial closing wedge ostectomy (CCWO) technique and to compare its efficacy to the standard technique on cadaveric specimens. METHODS: The standard and modified CCWO technique were applied to eight pairs of cadaveric tibiae. The following parameters were compared following the ostectomy: degrees of plateau levelling achieved (degrees), tibial long axis shift (degrees), reduction in tibial length (mm), area of bone wedge removed (cm²), and the area of proximal fragment (cm²). RESULTS: The size of the removed wedge of bone and the reduction in tibial length were significantly less with the modified CCWO technique. CLINICAL SIGNIFICANCE: The modified CCWO has two main advantages. Firstly a smaller wedge is removed, allowing a greater preservation of bone stock in the proximal tibia, which is advantageous for implant placement. Secondly, the tibia is shortened to a lesser degree, which might reduce the risk of recurvatum, fibular fracture and patella desmitis. These factors are particularly propitious for the application of this technique to Terrier breeds with excessive tibial plateau angle, where large angular corrections are required. The modified CCWO is equally effective for plateau levelling and results in an equivalent tibial long-axis shift. A disadvantage with the modified technique is that not all of the cross sectional area of the distal fragment contributes to load sharing at the osteotomy.

Tracking With a Hierarchical Partitioned Particle Filter and Movement Modelling.

We present an approach to track human subjects using an articulated human framework. First, we describe the articulated hierarchical human model. Second, we develop a stochastic hierarchical, partitioned, particle filter based on the natural structure and limb dependency of the human body. We apply this to track human subjects in video sequences using likelihoods adapted to the hierarchical process. Finally, we evaluate the effectiveness of the described approach using publicly available datasets.

A multicentre evaluation of the new Beckman Coulter anti-Mullerian hormone immunoassay (AMH Gen II).

BACKGROUND: The measurement of anti-Müllerian hormone (AMH) has been by two commercial enzyme-linked immunosorbent (ELISA) assays: Diagnostics Systems Laboratory (DSL 10-14400) and Immunotech (A11893 IVD EU only). Beckman Coulter has developed a new assay for AMH (AMH Gen II A79765), which uses the DSL antibodies but is standardized to the Immunotech calibration. As a result, comparative data are urgently required between the old DSL assay and its replacement AMH Gen II. METHODS: An evaluation of the AMH Gen II assay was performed at three sites, each with extensive experience of measuring circulating AMH in the adult female. Results were compared with the original DSL ELISA assay. The analysis was performed on a total of 271 patients' samples, approximately 90 at each site. RESULTS: Performance characteristics were evaluated for the AMHGen II assay. Linearity was acceptable with observed values close to the expected (mean recovery 106.3%). The functional sensitivity (20% coefficient of variation), calculated from precision profile data, was 1.5 pmol/L. Within- and between-batch imprecision, assessed over the concentration range of 5-70 pmol/L, were 5.3-11.4% and 3.8-17.3%, respectively. There was good agreement between assays with a Bablok-Passing regression equation AMH Gen II = 1.40 DSL-0.62 pmol/L, r = 0.96, n = 271. CONCLUSIONS: Our results demonstrate that similar precision and excellent between-assay agreement should be obtained when laboratories change from the DSL to the AMH Gen II ELISA and they should expect an increase in AMH values of approximately 40%.

Recent trends and clinical features of childhood vitamin D deficiency presenting to a children's hospital in Glasgow.

BACKGROUND: The incidence of vitamin D deficiency is unclear in the context of continuing demographic changes and the introduction of new public health measures. METHODS: All cases in which vitamin D deficiency was suspected as the primary cause of the clinical presentation were studied. RESULTS: Between 2002 and 2008, 160 cases of symptomatic vitamin D deficiency were identified with twice as many cases in 2008 (n, 42) as in the previous years. The median age of the cohort was 24 months (range 2 weeks-14 years).Three cases were recorded in children of European background, whereas the rest were in children of South Asian, Middle Eastern or sub-Saharan ethnic background. Presenting features included bowed legs in 64 (40%) and a fit in 19 (12%). In one infant, concerns were raised following a presentation with cardiac failure and hypocalcaemia. SUMMARY: Symptomatic vitamin D deficiency remains prevalent in the West of Scotland. There is a need for effective public health education, action and surveillance.

A screening procedure for primary aldosteronism based on the Diasorin Liaison automated chemiluminescent immunoassay for direct renin.

BACKGROUND: Primary aldosteronism (PA), the most common secondary cause of hypertension, can be screened for using the aldosterone/renin ratio. This ratio is raised in PA and its accuracy depends on the ability to measure plasma renin at extremely low concentrations. METHODS: We compared two different procedures for assessing plasma renin. The conventional method, which measures plasma renin activity (PRA), is technically demanding and laborious, and the Diasorin Liaison method, which measures plasma renin concentration (PRC), is an automated immunoassay. Results from each method were used to calculate the aldosterone/renin ratio (ARR) and the performance of the Diasorin Liaison method compared with that of the conventional assay using receiver operator characteristic curves. RESULTS: The analytical and functional sensitivity of the PRC method were 2.1 and 5 microIU/mL, respectively. Intra- and inter-assay precision were <7.2% and 10.4%, respectively. There was significant (9%) prorenin interference. Samples with PRA > 1.0 ng/mL/h showed significant correlation with PRC (r = 0.93; P < 0.05; n = 146); however, with PRA < 1.0 ng/mL/h, no significant correlation occurred (r = 0.14; P < 0.05; n = 79). An aldosterone (pmol/L)/PRC(microIU/mL) ratio of >35, in patients with aldosterone >300 pmol/L, resulted in 100% sensitivity and 93% specificity, when compared with the commonly accepted aldosterone (pmol/L)/PRA (ng/mL/h) ratio of >750, in identifying patients who may suffer from PA. CONCLUSION: This study indicates the feasibility of using the automated PRC assay as a replacement for the conventional manual PRA assay in calculating the ARR as a first-line screen for PA.

Measurement of 25-hydroxyvitamin D in the clinical laboratory: current procedures, performance characteristics and limitations.

In this review we describe procedures, performance characteristics and limitations of methods available for the measurement of 25-hydroxyvitamin (25OHD) since the year 2000. The two main types of methods are competitive immunoassay and those based on chromatographic separation followed by non-immunological direct detection (HPLC, LC-MS/MS). Lack of a reference standard for 25OHD has, until recently, been a major issue resulting in poor between-method comparability. Fortunately this should soon improve due to the recent introduction of a standard reference material in human serum (SRM 972) from the National Institute of Standards and Technology (NIST). For immunoassay, specificity can be an issue especially in relation to the proportion of 25OHD2 that is quantified whereas HPLC and LC-MS/MS methods are able to measure the two major vitamin D metabolites 25OHD2 and 25OHD3 independently. HPLC and LC-MS/MS require more expensive equipment and expert staff but this can be offset against lower reagent costs. Increasingly procedures are being developed to semi-automate or automate HPLC and LC-MS/MS but run times remain considerably longer than for immunoassays especially if performed on automated platforms. For most HPLC and LC-MS/MS methods extraction and procedural losses are corrected for by the inclusion of an internal standard which, in part, may account for higher results compared to immunoassay. In general precision of immunoassay, HPLC and LC-MS/MS are comparable and all have the required sensitivity to identify severe vitamin D deficiency. Looking to the future it is hoped that the imminent introduction of a standard reference method (or methods) for 25OHD will further accelerate improvements in between method comparability.

Exaggerated adrenarche in a cohort of Scottish children: clinical features and biochemistry.

OBJECTIVE: To investigate the reported association between exaggerated adrenarche (EA) and reduced foetal growth and to identify possible risk factors for future morbidity in Scottish children with clinical features of EA. DESIGN: Three-year prospective study. MEASUREMENTS: Auxology, blood pressure (BP), biochemical analysis of blood and urine, pelvic ultrasound in girls. RESULTS: Fifty-two patients were recruited of whom one girl had nonclassical congenital adrenal hyperplasia (17-OHP 17 nmol/l) and one had insufficient blood for analysis. The final cohort comprised 42 girls of mean (SD) age 7.7 (0.99) and eight boys of 8.8 (0.67) years. Mean (SD) birth weight was 3.27 (0.49) and 3.10 (0.76) kg in girls and boys respectively. Height/weight SDS were 1.13/1.69 in girls and 1.69/1.88 in boys. Mean systolic/diastolic BP was 107.8/60.4 (50th-75th centile) in girls and 115.5/63.9 (75th-91st centile) in boys. Uterine and ovarian development was prepubertal. Median serum dehydroepiandrosterone sulphate (DHEAS) was 2.1 and 4.1 mumol/l, androstenedione 3.1 and 3.8 nmol/l in girls and boys respectively, with DHEAS within the reference range/undetectable in 18/2 and androstenedione in 12/6 patients. Fasting insulin was 9.0 and 15.0 mU/l in girls and boys respectively, with concomitant low normal SHBG. Anti-Mullerian hormone (AMH) was 15.7 pmol/l in 27 girls, compared with 5.0 pmol/l in normal girls aged 5-8 years. CONCLUSIONS: Our Scottish EA cohort showed female predominance, no evidence of reduced foetal growth, a tendency to overweight with commensurate mild hyperinsulinaemia and modest elevation of serum androgens in some patients. We have found raised AMH levels in the girls, indicating advanced ovarian follicular development.

The concordance between serum anti-Mullerian hormone and testosterone concentrations depends on duration of hCG stimulation in boys undergoing investigation of gonadal function.

BACKGROUND: In boys undergoing investigation of gonadal function, the relationship between a single measurement of serum anti-Mullerian hormone (AMH) and hCG stimulated serum testosterone is unclear. AIM: The aim of the study was to assess concordance between serum AMH and testosterone concentrations following hCG stimulation of two different durations. METHODS: Samples from 284 children (M : F, 154 : 130) with a median age of 8 years (10th, 90th centiles, 0.25, 14) were used to establish an AMH reference range. Clinical data were reviewed in boys undergoing investigation of gonadal function and who had an AMH measurement and a hCG stimulated (3-day or 3-week) (n = 26) testosterone. Of these 26 boys, 11 had combined genital anomalies, whereas the rest had conditions such as isolated hypospadias, undescended testes or microphallus. Normal testosterone response to hCG stimulation was defined as a level greater than 3.5 nmol at day 4 and 9.5 nmol/l at day 22. RESULTS: In the reference group, the 5th centile AMH for boys below 1 year was 215 pmol/l and between 1 and 8 years 180 pmol/l. The 95th centile for girls for these respective age groups was 30 pmol/l and 25 pmol/l. In those cases where serum testosterone concentrations were available at day 1, day 4 and day 22 of the 3 week-hCG test, five cases had a normal serum testosterone at day 4 and three cases only showed such a response by day 22. In those where serum AMH was less than 180 pmol/l, a poor testosterone response of less than 3.5 nmol was observed in approximately seven of eight (88%) cases with a 3-day hCG stimulation test or the 3-week test. An AMH of greater than 180 pmol/l was associated with a normal testosterone response at day 4 in 10 out of 15 (67%) cases and at day 22 in eight of 11 (73%) cases. However, a low serum testosterone concentration of less than 3.5 nmol after the 3-day hCG test was only associated with a likelihood of a low AMH in three of eight (37%) cases. With the 3-week hCG test, a low day 22 testosterone of 9.5 mmol/l or less was associated with a low AMH of 180 pmol/l or less in four of seven (57%) cases. CONCLUSION: In boys undergoing investigation of gonadal function, the concordance between AMH and testosterone is better at day 22 than day 4. A normal AMH may provide useful information on overall testicular function but does not exclude the need for an hCG stimulation test.

Comparison of the prognostic value of tumour- and patient-related factors in patients undergoing potentially curative surgery for colon cancer.

AIM: To comprehensively compare the prognostic value of tumour- and patient-related factors in patients undergoing curative surgery for colon cancer. METHOD: From a database of 287 patients who underwent elective resection between 1997 and 2005, tumour factors including stage and host factors including systemic inflammatory response [modified Glasgow Prognostic Score (mGPS)] were identified. RESULTS: Median follow-up was 65 months. Over this period, 125 patients died, 80 from cancer. On multivariate analysis of all significant patient and tumour related factors, Dukes stage (P < 0.01), vascular invasion (P < 0.01) and the mGPS (P < 0.01) were independently associated with cancer-survival. Of the patient-related factors, age (P < 0.01), haemoglobin (P < 0.01), white-cell (P < 0.01), neutrophil (P < 0.01) and platelet (P < 0.01) counts, and alkaline phosphatase (P < 0.01) were most significantly associated with the mGPS. CONCLUSION: In addition to tumour-related factors such as Dukes stage and vascular invasion, the preoperative mGPS should be included to guide prognosis in patients undergoing curative resection for colon cancer.

Feline combined diaphyseal radial and ulnar fractures. A retrospective study of 28 cases.

Feline combined diaphyseal radial and ulnar fractures were reviewed in a retrospective study of cases that were admitted to two university teaching hospitals. A high incidence of complications was noted, with 6/26 (23.1%) of cases requiring revision surgery. Open fractures were significantly more likely to require revision surgery. The two main repair methods were external skeletal fixation (ESF) or radial plating. The success rate was greater for radial plating, with only 1/10 (10%) cases requiring revision versus 4/14 (28.6%) for ESF. However, ESF tended to be applied to the more complicated fractures. Stabilisation of both bones proved to be an effective repair strategy with only 1/8 cases (12.5%) requiring revision versus 5/18 cases (27.8%) where only one bone was stabilised. Synostoses and radiohumeral luxation were noted as complications associated with the fractures stabilised by ESF. Final limb function following recovery was assessed as 'good' or 'excellent' in 93.3% of cases.

A 5-year-old boy with cryptorchidism and pubic hair: investigation and management of apparent male disorders of sex development in mid-childhood.

BACKGROUND: Late presentation of congenital adrenal hyperplasia as a 46,XX disorder of sex development due to 11-beta hydroxylase deficiency is uncommon. Such a case raises issues regarding appropriate investigation and management. CASE HISTORY: A 5-year-old boy who had recently moved to the United Kingdom presented at the endocrinology clinic with recurrent abdominal pain. He was normotensive and had a history of ambiguous genitalia since birth, a relatively small penis, bilateral cryptorchidism and pubic hair. A systematic workup revealed low anti-Mullerian hormone levels for age and sex and elevated serum testosterone, androstenedione and deoxycortisol levels. A urinary steroid profile confirmed a diagnosis of 11-beta hydroxylase deficiency. The child's karyotype was 46,XX. Further genetic analysis revealed a compound heterozygote mutation in the CYP11B1 gene. Ultrasound scan showed evidence of Mullerian structures and accumulation of menstrual blood in the vagina (haematocolpos). Following discussion at a multidisciplinary clinic, the patient did not undergo sex reassignment and subsequently proceeded to surgery for removal of the Mullerian structures. CONCLUSIONS: This case emphasizes the importance of a systematic approach to investigation of older children presenting with apparent male undermasculinisation. It also raises important issues about gender reassignment in mid-childhood and the indications for removal of Mullerian organs in a 46,XX boy.