UK clinical guideline for the prevention and treatment of osteoporosis.

INTRODUCTION: In 2008, the UK National Osteoporosis Guideline Group (NOGG) produced a guideline on the prevention and treatment of osteoporosis, with an update in 2013. This paper presents a major update of the guideline, the scope of which is to review the assessment and management of osteoporosis and the prevention of fragility fractures in postmenopausal women and men age 50 years or over. METHODS: Where available, systematic reviews, meta-analyses and randomised controlled trials were used to provide the evidence base. Conclusions and recommendations were systematically graded according to the strength of the available evidence. RESULTS: Review of the evidence and recommendations are provided for the diagnosis of osteoporosis, fracture-risk assessment, lifestyle measures and pharmacological interventions, duration and monitoring of bisphosphonate therapy, glucocorticoid-induced osteoporosis, osteoporosis in men, postfracture care and intervention thresholds. CONCLUSION: The guideline, which has received accreditation from the National Institute of Health and Care Excellence (NICE), provides a comprehensive overview of the assessment and management of osteoporosis for all healthcare professionals who are involved in its management.

Degradation of oil by fungi isolated from Gulf of Mexico beaches.

Fungi of the Ascomycota phylum were isolated from oil-soaked sand patties collected from beaches following the Deepwater Horizon oil spill. To examine their ability to degrade oil, fungal isolates were grown on oiled quartz at 20°C, 30°C and 40°C. Consistent trends in oil degradation were not related to fungal species or temperature and all isolates degraded variable quantities of oil (32-65%). Fungal isolates preferentially degraded short (

The VCDQ--a Questionnaire for symptom monitoring in vocal cord dysfunction.

BACKGROUND: Vocal cord dysfunction (VCD) typically involves abnormal adduction of the vocal cords during inspiration, mimics the symptoms of asthma and leads to the prescription of ineffective medications. OBJECTIVE: We aimed to develop a clinical tool to monitor symptoms and response to treatment in confirmed VCD. METHODS: We collated symptoms of VCD from focus groups comprising patients and healthcare professionals; phrases describing these symptoms were assessed for face validity and internal correlation and rated for importance. The resultant 12-item questionnaire (VCDQ) rated the impact of each on a 5-point Likert scale (total score range 12-60) and was tested for reliability, concurrent validity and performance in 31 patients with endoscopically confirmed VCD (± asthma), 29 asthmatics with no history of VCD and 14 healthy controls. We assessed response to speech and language therapy and the minimal important difference by measuring the VCDQ pre- and post- therapy in a 20 new patients. RESULTS: The VCDQ had excellent test-retest reliability and differentiated VCD vs. healthy (Mann-Whitney U-test: z = -5.390, P < 0.001) and asthma (z = -5.730, P < 0.001). All patients improved post-therapy, assessed both by a global rating of change score (GRCS) and by the VCDQ [median (IQR) score pre-therapy 50.5 (48.0 - 54.8), post-therapy 35.0 (29.3 - 41.8), P < 0.001]. The minimal important difference in the VCDQ associated with a rating of 'minimally better' on the GRCS was 4 points. CONCLUSIONS AND CLINICAL RELEVANCE: The VCDQ is a valid and responsive tool suitable for measuring changes in symptoms in patients with VCD. It also gives insight into which symptoms are important to patients and could guide future therapy refinements. Future assessments of novel therapies for this condition should use an appropriately validated tool such as the VCDQ to measure response.

Post mortem cerebrospinal fluid α-synuclein levels are raised in multiple system atrophy and distinguish this from the other α-synucleinopathies, Parkinson's disease and Dementia with Lewy bodies.

Differentiating clinically between Parkinson's disease (PD) and the atypical parkinsonian syndromes of Progressive supranuclear palsy (PSP), corticobasal syndrome (CBS) and multiple system atrophy (MSA) is challenging but crucial for patient management and recruitment into clinical trials. Because PD (and the related disorder Dementia with Lewy bodies (DLB)) and MSA are characterised by the deposition of aggregated forms of α-synuclein protein (α-syn) in the brain, whereas CBS and PSP are tauopathies, we have developed immunoassays to detect levels of total and oligomeric forms of α-syn, and phosphorylated and phosphorylated oligomeric forms of α-syn, within body fluids, in an attempt to find a biomarker that will differentiate between these disorders. Levels of these 4 different forms of α-syn were measured in post mortem samples of ventricular cerebrospinal fluid (CSF) obtained from 76 patients with PD, DLB, PSP or MSA, and in 20 healthy controls. Mean CSF levels of total and oligomeric α-syn, and phosphorylated α-syn, did not vary significantly between the diagnostic groups, whereas mean CSF levels of phosphorylated oligomeric α-syn did differ significantly (p<0.001) amongst the different diagnostic groups. Although all 4 measures of α-syn were higher in patients with MSA compared to all other diagnostic groups, these were only significantly raised (p<0.001) in MSA compared to all other diagnostic groups, for phosphorylated oligomeric forms of α-syn. This suggests that this particular assay may have utility in differentiating MSA from control subject and patients with other α-synucleinopathies. However, it does not appear to be of help in distinguishing patients with PD and DLB from those with PSP or from control subjects. Western blots show that the principal form of α-syn within CSF is phosphorylated, and the finding that the phosphorylated oligomeric α-syn immunoassay appears to be the most informative of the 4 assays would be consistent with this observation.

Region-specific DNA methylation in the preimplantation embryo as a target for genomic plasticity.

It has been long known that the unique genetic sequence each embryo inherits is not the sole determinant of phenotype. However, only recently have epigenetic modifications to DNA been implicated in providing potential developmental plasticity to the embryonic and fetal genome, with environmental influences directly altering the epigenetic modifications that contribute to tissue-specific gene regulation. Most is known about the potential environmental regulation of DNA methylation, epigenetic addition of methyl groups to cytosine residues in DNA that acts in the long-term silencing of affected sequences. While most attention has been paid to the methylation of imprinted gene sequences, in terms of developmental plasticity there are many more parts of the genome that are methylated and that could be affected. This review explores the distribution of cytosine methylation in the genome and discusses the potential effects of regional plasticity on subsequent development. Widening our consideration of potentially plastic regions is likely to greatly enhance our understanding of how individuals are shaped not only by DNA sequence, but by the environment in which pluripotent embryonic cells are transformed into the many cell types of the body.

Protein Z, protein S levels are lower in patients with thrombophilia and subsequent pregnancy complications.

OBJECTIVE: We posit that low levels of protein S (PS) and protein Z (PZ) contribute to adverse pregnancy outcome (APO). PATIENTS: We evaluated 103 women with subsequent normal pregnancy outcome (NPO), 106 women with APO, and 20 women with thrombophilia (TP). METHODS: We compared first trimester (1st TRI) PZ levels in 103 women with NPO, 106 women with APO, and in 20 women with TP. We compared plasma levels of PZ and free PS antigen during the second (2nd TRI) and third trimesters (3rd TRI) of pregnancy in 51 women with APO and 51 matched women with NPO. RESULTS: The mean 1st TRI PZ level was significantly lower among patients with APO, compared to pregnant controls (1.81 +/- 0.7 vs. 2.21 +/- 0.8 microg mL(-1), respectively, P < 0.001). Of patients with known TP, those with APO had a tendency for lower mean PZ levels compared to those TP women with NPO (1.5 +/- 0.6 vs. 2.3 +/- 0.9 microg mL(-1), respectively, P < 0.0631). There was a significant decrease in the PZ levels in patients with APO compared to NPO (2nd TRI 1.5 +/- 0.4 vs. 2.0 +/- 0.5 microg mL(-1), P < 0.0001; and 3rd TRI 1.6 +/- 0.5 vs. 1.9 +/- 0.5 microg mL(-1), P < 0.0002). Protein S levels were significantly lower in the 2nd and 3rd TRIs among patients with APO compared to patients with NPO (2nd TRI 34.4 +/- 11.8% vs. 38.9 +/- 10.3%, P < 0.05, respectively; and 3rd TRI 27.5 +/- 8.4 vs. 31.2 +/- 7.4, P < 0.025, respectively). CONCLUSIONS: We posit that decreased PZ and PS levels are additional risk factors for APO.

The bacterial colonisation of silicone oil used in the management of wounds of the hands--a source of nosocomial infection?

For 30 years, silicone oil has been used for the management and rehabilitation of the injured hand. Its benefits accrue from its providing a non-irritant, bland, air-free medium in which the hand can undergo early movement, which prevents drying out of the tissues and helps in the separation of necrotic and infected tissue. It has been reported, however, that the silicone oil might act as a reservoir for nosocomial infection after two patients developed epidemic methicillin-resistant Staphylococcus aureus (EMRSA) infections. Since no firm guidelines exist with regard to open and/or infected wounds and the continued use of the same oil, a prospective study was set up to study the bacterial colonisation of the silicone oil. Thirty-five consecutive patients were entered into the study. The oil for each patient was changed each week but if any wound became clinically infected the oil was changed earlier. Treatment was continued until the wound was healed or until the treatment was stopped by the referring doctor. Bacteriology swabs taken from the wound and the oil before each treatment and from the oil after each treatment were analysed for bacterial colonisation. The results indicated that while bacteria were transferred into the oil from the wound, the inoculum was small and had no effect on wound healing. There was no evidence that wounds were being re-infected from the oil. The conclusion was that silicone oil remains a safe medium in which to exercise injured hands.

Hamato-lunate impingement: an uncommon cause of ulnar-sided wrist pain.

It has been reported that almost 50% of lunates have a separate medial facet on the distal surface for articulation with the hamate; about a quarter of these have erosion of the cartilage with exposed subchondral bone on the proximal pole of the hamate. We describe 4 cases of ulnar-sided wrist pain caused by hamato-lunate impingement that resulted in chondromalacia. The pain could be reproduced by a modification of the Lichtman test. The diagnosis was confirmed by arthroscopy. All 4 patients responded favorably to resection of the head of the hamate.

Of blood, inflammation and gunshot wounds: the history of the control of sepsis.

Galen (AD 129-199) propounded the notion that all wounds healed by second intention and the concept of laudable pus became unshakeable for almost 15 centuries. But William of Saliceto (AD ca 1210-1280) held quite firmly that pus formation was bad for both wound and patient and proclaimed that wounds should heal by first intention. The first rational theory of the nature of infection was by Fracastoro (1478-1553), a physician of Verona who regarded infection as being due to the passage of minute bodies from one person to another. But it was not until the work of Pasteur (1822-1895) that bacteriology took a significant leap forward. The association between bacteria and infection was slow to be accepted. The work of Semmelweis (1818-1865) is notable for his association between bacterial infection and puerperal fever. Lister (1827-1912) began the modern movement to control infection with his pioneering work in antiseptic surgery. Other contributions came from von Bergman (1836-1907; steam sterilization of instruments) and Halstead (1852-1922; rubber gloves for surgeons). The aseptic system has changed very little since then except for the innovations of Sir John Charnley (1911-1982; the laminar flow enclosure). The development of safe antibacterial drugs has been confined to the 20th century. This was led by Domagk (1895-1964; sulfonamides) and was followed by Sir Alexander Fleming (1881-1955), Sir Howard Walter Florey (1898-1968) and Sir Ernest Boris Chain (1906-1979; penicillin) and Selman Waksman (1888-1973; actinomycin).

Determination of testosterone and 6beta-hydroxytestosterone by gas chromatography-selected ion monitoring-mass spectrometry for the characterization of cytochrome p450 3A activity.

A method for the determination of testosterone and its metabolite, 6beta-hydroxytestosterone, in liver microsomal incubates employing gas chromatography with selected ion monitoring mass spectrometric detection (GC-SIM-MS) has been developed. The method is more rapid than previously reported methods. Testosterone and its metabolites are extracted from the incubation mixture in a single step with methylene chloride. The method does not require derivatization and testosterone and its metabolites are separated on a HP-5MS fused-silica capillary column in less than 15 min. The retention times of testosterone (m/z 288), methyltestosterone (m/z 302), and 6beta-hydroxytestosterone (m/z 304) are approximately 12.7, 12.8, and 13.4 min, respectively. There are no interferences from other known CYP450 metabolites of testosterone. In addition, the selectivity and specificity of the mass spectrometer helps eliminate possible interferences from drugs and new chemical entities evaluated using this methodology. Calibration curves for testosterone and 6beta-hydroxytestosterone are linear from 0.25 to 100 microM. Extraction recoveries are better than 92% for both analytes and the internal standard, methyltestosterone. Over the course of five separate runs, within-day and inter-day precision (expressed as relative standard deviation) was less than 5% for all concentrations of testosterone and 6beta-hydroxytestosterone. Accuracies ranged from 95.8 to 105.8% for testosterone and 94.6 to 104.2% for 6beta-hydroxytestosterone. The assay has been used to characterize the CYP3A metabolic activity of multiple preparations of human, rat, and dog liver microsomes.

Conservative and surgical treatment of tennis elbow: a study of outcome.

BACKGROUND: Tennis elbow is one of the most common lesions of the arm. The first description is attributed to Runge in 1873 but the name derives from 'Lawn Tennis Arm' described by Morris in 1882. The majority of cases are believed to be caused by a musculo-tendinous lesion of the common extensor origin at or near the attachment to the lateral epicondyle. While there are some comprehensive reports in the literature of patients treated by one technique or another, there are no comprehensive reports of groups of patients for whom various techniques were employed in a logical sequence until a resolution was reached. METHODS: This paper presents a retrospective analysis of case notes and an analysis of questionnaires completed by the patients. RESULTS: In this study we found that 67% of patients who presented with tennis elbow received relief through steroid injections either alone or in combination with a tennis elbow band or nonsteroidal anti-inflammatory drugs. The use of either a tennis elbow band or non-steroidal anti-inflammatory drugs or injected steroids made no statistical difference to the outcome. CONCLUSIONS: We also found that the patients who did not respond adequately to conservative measures were relieved of their symptoms by surgery.

Association of obesity, gender, age and occupation with carpal tunnel syndrome.

BACKGROUND: The present study determines the association of obesity, gender, age and occupation in patients with carpal tunnel syndrome (CTS) in a New Zealand population. METHODS: Analysis of questionnaires and clinical review of patients who had undergone surgical decompression of the median nerve in the carpal tunnel. RESULTS: The age and gender distribution of 655 hands (512 patients) that had undergone carpal tunnel release (CTR) were compared with the age and gender distribution of the New Zealand population. The results indicate that the 3-year-period prevalence of CTS in females is more than double that in males. Proportionally there were more patients over age 55 than in the general population. The findings also indicate that, proportionally, six times the number of females who worked in moderate manual work underwent CTR compared with the general female population and proportionally twice the number of males who worked in heavy office/clerical work underwent CTR compared with the general male population. It was also found that CTR patients are twice as likely to be overweight (body mass index [BMI] > 25) than the general population and female patients are twice as likely to be obese (BMI > 30) than the general population. CONCLUSIONS: Carpal tunnel syndrome is more than twice as common in females as it is in males, and patients aged more than 55 years are more likely to suffer from CTS. Females with CTS are more likely to work in moderate manual work and males with CTS are more likely to work in heavy office/clerical work. Obesity and CTS are related statistically.

Safety of silicone liquid in the postoperative management of Dupuytren's contracture.

BACKGROUND: Recently the New Zealand Department of Health expressed concerns about the safety of applying silicones to open wounds and banned their use. For 30 years silicone liquid has been used for the management and rehabilitation of the injured hand. It has been reported that the application of silicone fluids to the skin and ordinary handling over a period of years of various methyl and phenyl polymers by laboratory workers caused no skin disorders or sensitization, nor was absorption observed. There are no reports in the literature of the safety of the use of silicones applied to open wounds. METHODS: In the present study, 116 hands that had been mobilized in silicone liquid following surgery for Dupuytren's contracture over the last 12 years were reviewed. In the cases of 64 hands, the patients could be traced and contacted, and 47 patients (hands) agreed to attend for a clinical review. The hands were examined for areas of inflammation, granuloma formation and abnormal scar formation. RESULTS: No patient showed any evidence of adverse effects from the use of silicone liquid. CONCLUSIONS: There is no evidence that the use of silicone liquid, in contact with open wounds of the hands, for the mobilization of the hand following surgery for Dupuytren's contracture has any of the adverse effects reported as being associated with implanted silicone prostheses.

Results of open carpal tunnel release: a comprehensive, retrospective study of 188 hands.

BACKGROUND: Many recent reports of the results of decompression of the median nerve in the carpal tunnel have concentrated on only one aspect of recovery (numbness, grip etc.), and there are no reports of a comprehensive study of outcome. The aim of the present study was to review comprehensively the results of the direct visualization method of decompression of the carpal tunnel and to compare them with the published results of endoscopic release. METHODS: Patients' perceptions of the severity of pain, numbness and paraesthesiae due to carpal tunnel syndrome (CTS), before and after open carpal tunnel release (CTR) in 188 hands were reviewed retrospectively at a minimum time of follow-up of 18 months. Motor and sensory testing, provocation testing and measurement of scar tenderness in 135 hands were performed at a clinical review. RESULTS: Subjective results showed that 70% experienced a reduction in the severity of pain after CTR, 78% of hands experienced a reduction in the severity of paraesthesiae and 77% experienced a reduction in the severity of numbness. A total of 49% had improvements in all three symptoms after CTR. At the clinical review, sensory testing revealed that 59% of hands had normal or slightly diminished light touch, 35% had normal static two-point discrimination and 61% had normal dynamic two-point discrimination. Results for Tinel's test, Phalen's test and pressure provocation testing were positive in 10% of hands. There was no scar tenderness in 38%, no persisting thenar atrophy in 90%. Normal grip strength was found in 93% and 91% had normal pinch strength. CONCLUSIONS: It was concluded that open carpal tunnel release remains a safe and reliable treatment for carpal tunnel syndrome. The very low incidence of serious complications from the open technique of CTR, when compared with endoscopic CTR as published by different authors in the literature, and the comparable clinical results, appears to make the open technique a safer and preferable option. However, a properly controlled trial of both techniques is necessary to compare them.

Paraganglioma of the prostatic urethra. A report of three cases and a review of the literature.

OBJECTIVE: To determine the incidence and clinical presentation of prostatic urethral paragangliomas and to compare these findings with paragangliomas occurring in the other sites of the lower urinary tract. PATIENTS AND METHODS: The clinical records of three patients with prostatic urethral paragangliomas were reviewed, as was the histology of each specimen. The tumours were stained immunocytochemically with neuron-specific enolase, chromogranin, S100 protein, protein gene product 9.5, prostate-specific acid phosphatase and prostate-specific antigen. RESULTS: The three tumours occurred in elderly men, two of whom presented with haematuria, one of whom also had a vesical transitional cell carcinoma, and the third patient had obstructive symptoms due to co-existent prostatic hyperplasia. The histological appearances and immunocytochemical findings were consistent with paraganglioma. Treatment consisted of local excision and there were no recurrences or metastases at 5 and 6 years in two patients for whom follow-up was available. CONCLUSION: Urethral paragangliomas are rare tumours arising in elderly men and are hormonally inactive. Although haematuria may be the presenting symptom, it is important to exclude additional more common and possibly more sinister lesions such as transitional cell carcinoma. Local excision appears to be curative.