Primary bone marrow oedema syndromes.

MRI scanning in patients with rheumatological conditions often shows bone marrow oedema, which can be secondary to inflammatory, degenerative, infective or malignant conditions but can also be primary. The latter condition is of uncertain aetiology and it is also uncertain whether it represents a stage in the progression to osteonecrosis in some patients. Patients with primary bone marrow oedema usually have lower limb pain, commonly the hip, knee, ankle or feet. The diagnosis is one of exclusion with the presence of typical MRI findings. Treatment is usually conservative and includes analgesics and staying off the affected limb. The natural history is that of gradual resolution of symptoms over a number of months. Evidence for medical treatment is limited, but open-label studies suggest bisphosphonates may help in the resolution of pain and improve radiological findings. Surgical decompression is usually used as a last resort.

National Osteoporosis Society vitamin D guideline summary.

The National Osteoporosis Society (NOS) published its document, Vitamin D and Bone Health: A Practical Clinical Guideline for Patient Management, in 2013 as a practical clinical guideline on the management of vitamin D deficiency in adult patients with, or at risk of developing, bone disease. There has been no clear consensus in the UK on vitamin D deficiency its assessment and treatment, and clinical practice is inconsistent. This guideline is aimed at clinicians, including doctors, nurses and dieticians. It recommends the measurement of serum 25 (OH) vitamin D (25OHD) to estimate vitamin D status in the following clinical scenarios: bone diseases that may be improved with vitamin D treatment; bone diseases, prior to specific treatment where correcting vitamin D deficiency is appropriate; musculoskeletal symptoms that could be attributed to vitamin D deficiency. The guideline also states that routine vitamin D testing is unnecessary where vitamin D supplementation with an oral antiresorptive treatment is already planned and sets the following serum 25OHD thresholds: <30 nmol/l is deficient; 30-50 nmol/l may be inadequate in some people; >50 nmol/l is sufficient for almost the whole population. For treatment, oral vitamin D3 is recommended with fixed loading doses of oral vitamin D3 followed by regular maintenance therapy when rapid correction of vitamin D deficiency is required, although loading doses are not necessary where correction of deficiency is less urgent or when co-prescribing with an oral antiresorptive agent. For monitoring, serum calcium (adjusted for albumin) should be checked 1 month after completing a loading regimen, or after starting vitamin D supplementation, in case primary hyperparathyroidism has been unmasked. However, routine monitoring of serum 25OHD is generally unnecessary but may be appropriate in patients with symptomatic vitamin D deficiency or malabsorption and where poor compliance with medication is suspected. The guideline focuses on bone health as, although there are numerous putative effects of vitamin D on immunity modulation, cancer prevention and the risks of cardiovascular disease and multiple sclerosis, there remains considerable debate about the evaluation of extraskeletal factors and optimal vitamin D status in these circumstances.

T helper cell subsets in arthritis and the benefits of immunomodulation by 1,25(OH)2 vitamin D.

The prevalence of vitamin D deficiency has been shown to be increased in many of the common arthritides. Importantly, vitamin D has significant immunomodulatory effects in addition to its role in calcium homoeostasis. Both aspects of its function have a major bearing on joint disease whether as part of an inflammatory arthritis or from wear and tear. While the exact mechanisms still require clarification, there is now compelling evidence that the hormonally active 1,25-dihydroxycholecalciferol vitamin D can reduce the activity of the proinflammatory Th1 and Th17 T cell subsets. Additionally, it is stimulatory of enhanced anti-inflammatory Th2 activity at the same time as promoting T regulatory cell activity. These various actions suggest that correcting vitamin D deficiency should be a important part of the management of all patients with joint disease. For the future, vitamin D analogues with enhanced immunomodulatory properties but with reduced ability to increase calcium are being investigated.

Changes in bone mineral parameters, vitamin D metabolites, and PTH measurements with varying chronic kidney disease stages.

Vitamin D deficiency is associated with an increased risk of many diseases (skeletal and nonskeletal). Emerging data also associate high concentrations of serum parathyroid hormone (PTH) with morbidity and increased mortality in patients both with and without known chronic kidney disease (CKD). Understanding the relationship between vitamin D and PTH and the determinants of PTH is therefore important. We performed a cross-sectional study of 203 patients with varying stages of CKD randomly recruited from the Renal Unit database at our institution. Detailed case review was performed, and samples of fasting blood were taken for biochemical analyses. We measured standard biochemistry, 25-hydroxyvitamin D (25-OHD), 1,25-OHD, and three PTH measurements [1-84 PTH, total PTH, and derived N-terminal truncated, 7-84 PTH (cPTH)]. Vitamin D deficiency was high, with 86% of patients having 25-OHD levels below 30 ng/ml. Estimated glomerular filtration rate (eGFR) was not associated with 25-OHD levels, whereas 1,25-OHD was lower in those with CKD stage 5 versus stage 4, who were not treated with vitamin D metabolites (18 vs. 65 pg/ml, respectively; P < 0.05). All three PTH measurements increased with worsening eGFR, with this finding being more pronounced in those patients who were not treated with vitamin D metabolites. The slope of the regression line of cPTH on eGFR tended to be steeper, -0.90, compared to -0.81 for total PTH and -0.80 for 1-84 PTH (P = 0.06). The ratio of total PTH to cPTH did decrease significantly through the range of CKD stages (P = 0.03). The determinants of PTH were similar for all three PTH measurements, with eGFR having a strong inverse relationship, with weaker relationships for 25-OHD and ionized calcium on multivariate analyses. We confirm that there is a complex relationship between 25-OHD, eGFR, and PTH. Total PTH, 1-84 PTH, and cPTH increase with increasing CKD stages, with a relatively greater increase in cPTH, although the clinical significance of this finding remains uncertain. The three PTH measurements had similar correlations with the biochemical and clinical variables studied, suggesting that either total PTH or 1-84 PTH can be used in clinical practice when evaluating vitamin D and PTH status.

Leptin: linking obesity, the metabolic syndrome, and cardiovascular disease.

The incidence and prevalence of obesity and the metabolic syndrome have risen markedly in the past decade, representing a serious cardiovascular health hazard with significant morbidity and mortality. The etiology of the metabolic syndrome and its various pathogenic mechanisms are incompletely defined and under intense investigation. Contemporary research suggests that the adipocyte-derived hormone leptin may be an important factor linking obesity, the metabolic syndrome, and cardiovascular disorders. Although recent evidence indicates that under normal conditions leptin may be an important factor in regulating pressure and volume, during situations of chronic hyperleptinemia and leptin resistance, this hormone may function pathophysiologically for the development of hypertension and cardiac and renal diseases. Future research will determine if reduction of circulating leptin and/or blockade of its peripheral actions can confer cardiovascular and renal protection in hyperleptinemic patients with obesity and the metabolic syndrome.

Hearing difficulties are common in patients with rheumatoid arthritis.

Rheumatoid arthritis (RA) is well known to affect many different organ systems. Previous work suggests that this includes the auditory system and that measures of hearing may be related to indices of RA disease activity. The aims of this study were to determine whether hearing loss in young subjects with rheumatoid arthritis is greater than would be expected in the normal population and whether disease activity or duration correlate with hearing levels. About 55 patients (less than 50 years old) with RA were sampled from a secondary-care-level population. Pure-tone audiograms, transient evoked otoacoustic emissions (TEOAEs) and rheumatological assessment including disease duration and the DAS28 disease activity score were carried out. Subjective hearing loss was a common symptom with a prevalence of 29.6% (95% CI 17.8-42.2%). The prevalence of conductive hearing loss was 1.9% (95% CI 0.3-9.7%)). Subjects with RA had worse hearing than expected at low and middle frequencies (250 Hz to 2 kHz). TEOAEs were absent in 15 of 84 (18%, 95% CI 11-27%) normal ears. No relationship was demonstrated between hearing thresholds and markers of disease activity or other rheumatological parameters. Hearing loss is common in young people with RA and should be sought by clinicians caring for this patient population. TEOAEs are absent in a higher proportion of patients than expected, and this may be a marker of early asymptomatic hearing loss. It may be conductive or sensorineural and may take any configuration, including low-frequency loss.

Obesity-hypertension: emerging concepts in pathophysiology and treatment.

The incidence and prevalence of obesity has risen markedly in the last decade, and this epidemic represents a serious health hazard with significant morbidity and mortality. Although hypertension is recognized as one of the most serious consequences of obesity, its pathophysiology remains incompletely understood. Contemporary research suggests that the recently discovered hormone leptin may represent a common link between these 2 pathologic conditions. Leptin is primarily synthesized and secreted by adipocytes. One of the major functions of this hormone is the control of energy balance. By binding to receptors in the hypothalamus, it reduces food intake and promotes elevation in temperature and energy expenditure. In addition, increasing evidence suggests that leptin, through both direct and indirect actions, may play an important role in cardiovascular and renal functions. Although the relevance of endogenous leptin needs further clarification for the control of renal sodium excretion and vascular tone, it appears to be a potential pressure and volume-regulating factor in normal situations. However, in conditions of chronic hyperleptinemia, such as obesity, leptin may function pathophysiologically for the development of hypertension as well as cardiac and renal disease. Thus, in addition to weight control, reduction of circulating leptin may confer cardiovascular and renal protective effects in patients with obesity-hypertension.

Electrocardiographic diagnosis of left ventricular hypertrophy: the effect of left ventricular wall thickness, size, and mass on the specific criteria for left ventricular hypertrophy.

BACKGROUND: The purpose of our study was to determine the relative importance and effect of an increased left ventricle wall thickness, left ventricular diastolic diameter, and left ventricular mass (LVM) on the performance of the 4 major electrocardiogram (ECG) criteria of left ventricular hypertrophy (LVH) and to determine how these findings could be incorporated into the routine ECG interpretation of LVH. METHODS: The ECG criteria of LVH that we chose to examine were voltage, repolarization abnormalities, left atrial abnormality, and ventricular conduction time. We analyzed data from 608 consecutive patients with left ventricular wall thickness of >13 mm on the echocardiogram and with a concurrent ECG. We arbitrarily divided patients into 3 groups (groups I-III) according to the calculated LVM. Group I had an LVM of <400 g; group II had an LVM from 400 to 600 g, and group III had an LVM of >600 g. We evaluated the effect of increasing LVM, wall thickness, and ventricular diameter on the performance of the 4 ECG criteria at different severity of thickness, diameter, and mass. RESULTS: An increase in the echocardiogram-derived LVM had significant effect on all 4 ECG criteria. As LVM progressively increased from groups I to III, the frequency of voltage criteria for LVH increased from 52% to 83%; left atrial abnormality rose from 46% to 68%; ST-T wave changes increases from 55% to 95%, and QRS prolongation significantly increased from 42% to 70%. CONCLUSION: Increased wall thickness and ventricular diameter failed to correlate with the overall ECG score or significantly influence the frequency of any of the 4 ECG criteria for LVH in patients when LVM was held relatively constant. We also demonstrated that an increasing number of criteria on the ECG are associated with a greater mean LVM.

Massive septic thrombus formation on a superior vena cava indwelling catheter following Torulopsis (Candida) glabrata fungemia.

Fungal endocarditis is an exceedingly rare complication of indwelling central venous catheters in adults. Here we describe what appears to be the first case of a right atrial thrombus superinfected with the yeast Torulopsis (Candida) glabrata and attached to an indwelling superior vena cava catheter that was not used for parenteral nutrition. A large vegetation-like mass adherent to the catheter tip was visualized by transesophageal echocardiography in a patient who presented with signs of septic pulmonary embolism. Following open-heart surgery, the definitive diagnosis was established by histopathologic examination of the surgical specimen.

Use of the X-SIXER catheter system in the treatment of acute thrombotic coronary occlusion.

The X-SIZER thromboatherectomy catheter system (EndiCOR Medical, Inc.) was initially developed for the treatment of thrombus in acute coronary syndromes. We present the case of a 64-year-old man with thrombotic occlusion of the left circumflex coronary artery. Antegrade flow was restored by aspiration of platelet thrombus at the point of occlusion, although the catheter was unable to cross the underlying stenosis. Its limited ability to cross severe stenoses or reduce lesion severity suggests that the X-SIZER should not be regarded as an atherectomy device. However, this case report suggests that the X-SIZER device has potential as an adjunct to PTCA and stenting in reducing the risk associated with thrombotic occlusion.

Microbial quality of water supply to an urban community in Trinidad.

A microbiological study was conducted to determine the quality of the water supply to an urban community in San Fernando proper in south Trinidad using total coliforms and thermotolerant coliforms as indicators of water pollution. The membrane filter technique was used to detect total coliforms and thermotolerant coliforms on endo agar and MFc agar, respectively. The residual chlorine levels in water from the reservoir, from standpipes along the distribution line, and from households were determined with a commercial test kit. Of a total of 104 drinking water samples obtained from households, 84 (80.8%), 56 (53.8%), and 70 (67.3%) tested positive for total coliforms, thermotolerant coliforms, and Escherichia coli, respectively. The difference was statistically significant (P < 0.05, chi2). Of the 81 water samples collected from the Water and Sewerage Authority (WASA) main supply to households, 38 (46.9%), 13 (16.0%), and 27 (33.3%) were contaminated by total coliforms, thermotolerant coliforms, and E. coli, respectively, and the difference was statistically significant (P < 0.05, chi2). Eight (20.5%) of 39 water samples from standpipes along the distribution line tested positive for total coliforms, compared with 4 (10.3%) samples testing positive for thermotolerant coliforms. All five samples of treated water obtained from the reservoir tested negative for coliforms. There was a significant difference (P = 0.004) in the mean residual chlorine levels in water from the reservoir, water from standpipes, and water from households. Similarly, as the level of residual chlorine decreased, there was a statistically significant (P = 0.004) increase in the prevalence of total coliforms in water from 0.0% (treated reservoir water) to 15.2% (standpipe) to 53.5% (household mains) to 80.0% (household drinking water). There was also a statistically significant difference (P < 0.001, chi2) in the prevalence of total coliforms in drinking water and in water from the WASA main supply to households. Of the 105 E. coli strains tested, 7 (6.7%), 16 (15.2%), and 22 (21.0%) were mucoid, hemolytic, and non-sorbitol fermenters, respectively. It was concluded that the high degree of contamination of drinking water in households poses a health hazard to consumers.

Risk factors for fractures and falls in older women with type 2 diabetes mellitus.

Type 2 diabetes mellitus (DM) is associated with an increased risk of hip fractures despite patients with this condition having normal to high bone mineral density (BMD). Therefore, nonskeletal risk factors may be important in the etiology of fractures in these patients. The aim of this cross-sectional retrospective study was to determine risk factors for falling and fracture in older women with type 2 DM. We randomly recruited 150 women from a community-based diabetes register. They underwent detailed clinical assessment, and BMD was measured by dual-energy X-ray absorptiometry (DXA) and heel quantitative ultrasound (QUS). Mean age was 74 years, mean duration of DM 11 years, mean body mass index 30 kg/m2, and mean HbA1c 7.6%. Mean BMD Z scores were significantly higher than the manufacturer's reference range for all skeletal sites. Previously, 53/150 (35%) of the women had reported a low trauma fracture. The fracture group did not differ significantly from the nonfracture group by age, diabetes-related risk factors or DXA BMD Z scores. However, QUS variables were lower in the fracture group (P = 0.04). A history of one or more falls in the previous 12 months was reported by 61/89 (41%) women. Fallers had a higher vibration perception threshold vs. nonfallers (mean 21.1 vs. 17.6 volts, respectively; P = 0.05). There were no other differences in diabetes or fall-related risk factors. These data suggest that reduced vibration perception (a measure of peripheral neuropathy) is an important risk factor for falling and that QUS, as opposed to DXA, may be a more useful method for fracture risk prediction in older women with type 2 DM. These findings need to be confirmed prospectively.

Association between serum vitamin D metabolite levels and disease activity in patients with early inflammatory polyarthritis.

OBJECTIVE: Previous in vitro and animal studies have suggested that vitamin D, in particular, its metabolite 25-hydroxyvitamin D (25[OH]D), may have immunomodulatory effects. To study further the potential immunomodulatory effects of vitamin D in humans, we explored the hypothesis that serum vitamin D metabolites may be inversely associated with current disease activity, severity, and functional disability in patients with early inflammatory polyarthritis (IP). METHODS: We studied 206 consecutive patients with IP who were enrolled in the Norfolk Arthritis Register between January 2000 and November 2003 inclusive. Patients were studied within 6 months of symptom onset. None of the patients was taking steroids, and all had received <6 weeks of disease-modifying therapy. Associations between serum levels of 25(OH)D and 1,25-dihydroxyvitamin D (1,25[OH](2)D) at baseline and the swollen and tender joint counts, Health Assessment Questionnaire (HAQ) scores, C-reactive protein (CRP) levels, and the Disease Activity Score 28-joint assessment (DAS28) scores at baseline and 1 year were assessed. RESULTS: The median age at symptom onset was 59 years (range 20-88 years), with a median disease duration of 4 months. At baseline, there was an inverse relationship between 25(OH)D levels and the tender joint count, DAS28 score, and HAQ score. The only inverse relationship with 1,25(OH)(2)D was with the HAQ score. Each 10-ng/ml increase in the level of 25(OH)D was associated with a decrease in the DAS28 score of 0.3 and in the CRP level of approximately 25%. At 1 year, the only significant result was an inverse association between baseline vitamin D metabolite levels and the HAQ score; that is, those with higher metabolite levels had lower HAQ scores. CONCLUSION: These data provide further support that vitamin D plays an immunomodulatory role in inflammatory arthritis. This association needs to be examined in other cohorts of patients with early IP, as well as in longitudinal studies. If confirmed, the clinical response to vitamin D supplementation should be examined in early IP.

Fall-related risk factors and osteoporosis in older women referred to an open access bone densitometry service.

OBJECTIVE: Both falls and low bone density are important in the pathogenesis of osteoporotic fractures. Whilst bone density is routinely measured to assess fracture risk, little attention is given to the assessment of fall risk. In this study we have determined the prevalence and explored relationships between fall-related risk factors and osteoporosis in women referred to our open access bone densitometry service. DESIGN: Cross-sectional study. SETTING: Teaching hospital in south-west London, UK. SUBJECTS: Older women referred for open access bone densitometry. MEASUREMENTS: Bone densitometry by dual-energy X-ray absorptiometry and fall risk assessment (visual acuity, ability to do five stand-ups without arm use and ability to perform heel-toe walking). RESULTS: Data for 558 women seen over an 18 month period were examined. Their mean age was 74.8 years (range 65-93). Fall risk and femoral neck (FN) osteoporosis increased with age, with fall-related risk factors being more prevalent than FN osteoporosis at each tertile of age. Women with both FN osteoporosis and fall-related risk factors ranged from 7% in the youngest tertile to 22% in the oldest tertile. In women with FN osteoporosis, increased fall risk was found in 37% in the youngest tertile, increasing to 63% in the oldest tertile. CONCLUSIONS: Fall-related risk factors are common in older women referred for open access bone densitometry. We recommend that both bone density and fall risk assessment, using simple screening tests for falls, are essential to determine fracture risk in older people referred for bone densitometry. Subsequent management to reduce fracture risk should be individualised for each patient.

A prospective study of changes in bone turnover and bone density associated with regaining weight in women with anorexia nervosa.

Anorexia nervosa (AN) is a condition of self-induced weight loss, associated with an intense fear of gaining weight. Previous studies have shown that bone density may increase with regaining and maintaining normal weight; however, relatively little is known about the changes in bone metabolism that occur during weight restoration. We describe the effect of weight restoration and maintenance of weight over 1 year on bone mineral density (BMD) and bone turnover. We recruited women from the eating disorders services at the South West London and St George's Mental Health NHS Trust, and the Priory and Charter Nightingale Hospitals in London, UK. Details of their AN, fracture history, menstrual history and exercise were obtained by interview and case note review. Morning samples of blood and second void urine were taken for biochemical analysis. BMD was measured by DXA at the lumbar spine (LS), femoral neck (FN), distal radius (RD) and total body bone mineral content (BMC). Patients then entered the treatment program, which includes re-feeding, dietary education and psychotherapy. Over a period of 42 months, we recruited 55 women who agreed to participate in this study and underwent baseline investigations. Of these, 15 (27%) subjects achieved and then maintained their target weight for the duration of the study. At baseline for all subjects (n=55) estradiol levels were lower than the normal reference ranges (both follicular and luteal phases) in 91% of the women. Bone specific alkaline phosphatase (BSAP) concentrations were lower than the premenopausal reference range in 55% of women, and urinary deoxypyridinoline (DPD) was above the premenopausal reference range in 78% of women. Baseline lumbar spine BMD was positively related to BMI (Pearson's r=0.29, P=0.04) and inversely related to bone turnover markers: urinary DPD (Pearson's r=-0.39, P=0.01 and serum BSAP (Pearson's r=-0.3, P=0.06). The 15 patients who regained and maintained weight were followed-up for a mean duration of 69 weeks (SD 7.3, range 54 to 84 weeks). Mean BMI increased from 14.2 (1.7) to 20.2 (0.77) kg/m2 and remained stable throughout follow-up. Menstruation resumed in 8 of the 15 women. Total body BMC and LS BMD increased significantly over the duration of follow-up (by 4.3% each), but FN BMD and distal radius remained stable. Lumbar spine bone area also increased significantly, whereas FN and distal radius did not. These changes were associated with a significant increase in BSAP (P=0.01), and a non-significant trend for a decrease in DPD (P=0.10). Our findings suggest that when women are at low body weight they are in a hypo-estrogenic state, which is associated with imbalance of bone turnover (high bone resorption and low bone formation). This is reversed with weight gain and persists as target weight is maintained and is associated with increases in BMC and BMD.