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.

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.

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.

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 (

Purification and properties of parathyroid hormone-related peptide isolated from milk.

The occurrence and properties of PTH-related peptide (PTH-RP) in milk was investigated. PTH-RP was purified to homogeneity from human and bovine milk using heat and acid to precipitate milk proteins followed by ion exchange chromatography and reverse-phase HPLC. The peak of PTH-RP from HPLC was detected using a sensitive bone cell bioassay. A single band of peptide was detected on silver-stained polyacrylamide gels, which migrated as a 20-21-kDa macromolecule. PTH-RP isolated from either human or bovine milk had similar electrophoretic mobilities on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The partially purified bovine PTH-RP stimulated cAMP production in UMR106-01 and OK cell lines and elicited a concentration-dependent inhibition of sodium-dependent phosphate transport in OK cells. Incubation of milk extracts with an anti-PTH antiserum did not affect their bioactivity, whereas an antihuman PTH-RP 1-34 antiserum markedly reduced the cAMP response of UMR106-01 cells to the immunoabsorbed milk extracts. A PTH antagonist, norleu PTH 3-34, blocked the stimulation of cAMP production in UMR106-01 cells treated with milk extracts. PTH-RP immunoreactivity and bioactivity occurred in milk extracts of diverse animals from both eutherian and metatherian (marsupial) species. Porcine colostrum also had immunoreactive PTH-RP, although the levels were lower than the immunoreactive PTH-RP concentrations observed in milk samples collected at 7 and 14 days of lactation. Thus, a 20-21-KDa PTH-RP is secreted into milk where it could play a role in the development of suckling, newborn animals.

Bovine parathyroid tissue: a model to compare the biosynthesis and secretion of parathyroid hormone and parathyroid hormone-related peptide.

Bovine parathyroid tissue was evaluated as a model to compare parathyroid hormone-related peptide (PTH-rP) and parathyroid hormone (PTH) secretion. Tissue was incubated in variable calcium levels (n = 5). A parathyroid cell digest was prepared from collagenase-treated glands. PTH-rP and PTH levels were determined by radioimmunoassay. PTH-rP bioactivity was determined by 3H-cAMP production in a UMR 106 cell bioassay. PTH-rP levels in the incubation medium were 2.0 ng/mg protein (0.25 mmol Ca++), 2.2 ng/mg protein (1.25 mmol Ca++), and 1.9 ng/mg protein (2.5 mmol/L Ca++). PTH levels were 321 ng/mg protein (0.25 mmol/L Ca++) and 200 ng/mg protein (2.5 mmol Ca++). Therefore, calcium significantly inhibited PTH but not PTH-rP secretion (p = 0.03). Addition of incubation medium to the bioassay resulted in 3H-cAMP levels that were 8 to 10 times greater than basal levels. Greater than 50% of the activity persisted after addition of PTH antibody, demonstrating that a significant amount of the activity was caused by PTH-rP. Tissue PTH-rP was 5.1 ng/mg protein, compared with 2080 ng/mg protein for PTH. We conclude that (1) bovine parathyroid tissue contains bioactive PTH-rP and is a useful model to compare the biosynthesis and secretion of PTH-rP and PTH in normal tissue and (2) unlike PTH, PTH-rP secretion is not regulated by calcium.

Bizarre parosteal osteochondromatous proliferation of the hand in a young man.

We report a case of a solitary osteochondromatous tumor on the hand of a 38 yr old man. This had radiological and histological features distinct from an osteochondroma and demonstrated the features first described as bizarre parosteal osteochondromatous proliferation. These lesions have a tendency for local recurrence but no metastatic behaviour has yet been reported. We highlight 2 histological features which have not been previously described.

Spinal and pelvic kinematics in osteoarthrosis of the hip joint.

Angular displacement of the pelvis and the lumbar spine was measured in a group of 19 patients with unilateral osteoarthrosis of the hip joint and a group of 10 control subjects of similar ages for comparison, and the means for each were calculated. All of the patients showed an increase in both sagittal plane (P less than 0.005) and coronal plane (P less than 0.01) movements of the pelvis, when compared with the control group. Two patterns of spinal movement were evident. One group showed a significant decrease in coronal plane movements and the other group showed a significant increase in coronal plane movements. Characteristic patterns of movement were identified and the variations between different patients recorded.

Normal kinematics of the lumbar spine and pelvis.

A study was undertaken to provide a data base of pelvic and lumbar spinal movement during walking. The movements of the pelvis and lumbar spine in 48 male volunteers of age range 16 to 74 years were measured using a television/computer motion analysis system. The results were presented both as a range of movement in each plane and as a wave pattern for the movement in each plane. Cadence, the movements of the pelvis and spine in the sagittal plane, and the movement of the pelvis in the transverse plane all showed a negative correlation with age. Analysis of the wave patterns showed that the movements of the pelvis and lumbar spine relate to identifiable events in the gait cycle.

Pivot osteotomy for the correction of malunion of metacarpal neck fractures.

A new configuration of osteotomy has been developed which combines the principles and benefits of opening and closing wedge osteotomies without the degree of shortening associated with the closing wedge osteotomy and the tension imposed on the soft tissues by the opening wedge osteotomy. It is ideally suited to the correction of angular malunions in the long bones of the hands. Ten osteotomies of malunions of the metacarpals have been performed in nine hands giving good correction of the malunion in all cases.

Conservative surgery for Dupuytren's contracture.

The trend towards conservativism in the management of Dupuytren's contracture has resulted in less radical surgery than was previously advocated to release disabling contractures of the fingers. 38 cases of Dupuytren's contracture in the palm have been treated by Z-plasty of skin and underlying contracted band without fasciectomy. Proximal interphalangeal joint contractures were treated by fasciectomy and skin closure with Z-plasties as required. Only one of 16 patients reviewed after two years had evidence of recurrence. Skin compliance has been measured and a return to near-normal levels was found in all but the one patient with a recurrence.

The possible role of vascular congestion in carpal tunnel syndrome.

A study of interstitial pressures within the carpal tunnel using a slit catheter found that, in some patients, an initial rise in pressure is recorded when the wrist is passively extended and this continues to rise to a plateau if the position is maintained. A rise above a critical pressure brought about by congestion would explain the clinical picture of predominantly nocturnal symptoms and no electro-physiological evidence with the wrist in a neutral (resting) position. The results also bring into doubt published results of the pressure within the carpal tunnel with the wrist flexed or extended, since the pressure can be changed at will, depending on the flexion or extension force used.

Clinical fracture of the carpal scaphoid--an illusionary diagnosis.

The management of patients with clinical evidence of a fracture of the carpal scaphoid bone but without radiological evidence of a fracture is based on dogma emphasizing the need to immobilize the wrist in all cases. Because of the apparently high proportion of patients who spend up to six weeks in a plaster cast and in whom no fracture is ever demonstrated radiologically, a study was undertaken to determine the fate of those wrist injuries diagnosed as clinical fractures of the scaphoid. All patients who presented with clinical or radiological evidence of fractures of the scaphoid over a one year period were reviewed. Of the 108 patients in whom the diagnosis of clinical fracture of the scaphoid was made at the time of presentation none was proved radiologically to have a fracture of the scaphoid subsequently after a period of mobilization. These patients spent an average time of 21.9 days in a plaster cast which represents a significant loss of productivity to the community and inconvenience to the patient.

Tourniquet pressure: the effect of limb circumference and systolic blood pressure.

Complications attributable to direct pressure may result from the use of pneumatic tourniquets during surgical procedures. Traditional estimates have determined the pressures employed rather than the minimal pressure necessary to produce a bloodless field. To determine this pressure, pre-operative and post-operative systolic blood pressures and the tourniquet pressure at which capillary bleeding occurred were measured in a group of patients undergoing elective surgery of the upper and lower limbs. From these results two equations were derived, one for each of the upper and lower limbs, which give the minimum tourniquet pressures to produce bloodless fields. In an average sized, normotensive patient, 200mm Hg was found to be adequate for the upper limb and 250mm Hg for the lower limb.

Foot injuries caused by power lawn mowers.

Seventeen cases of foot injury caused by power lawn mowers are reviewed. Eleven patients were using an air-cushion type of mower. None was wearing adequate protective footwear. The types of injuries sustained and their long term problems are discussed. The need for user safety and education is stressed.

Congenital dislocation of hip in the newborn: a postnatal survey.

The results of a postnatal survey carried out for congenital dislocation of hip in children born at the Wellington Hospital maternity unit over a ten year period is presented. Of the 15,000 neonates born during this period, 91% underwent hip examinations. Abnormality was recorded 1.8% (n = 247) 78% (n = 192) of whom had clinically stable hips when re-checked seven to ten days later. In all, 60 children had unstable hips requiring definitive treatment, five of whom missed the neonatal screening and presented late. In this latter group, 77% (n = 46) had normal hips by six months of age following conventional splintage. Eight point two percent (n = 5) were unstable after six months of splintage, 5% (n = 3) were lost to follow-up, 1.6% (n = 1) presented late and in 8.2% (n = 5) the hip examination was either not done or instability not detected. We conclude that, in spite of the great awareness and known long term benefits of early neonatal hip examinations, late presentations because of missed examinations continue to be significant.

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.