Fracture risk among older men: osteopenia and osteoporosis defined using cut-points derived from female versus male reference data.

SUMMARY: We explored the effect of using male and female reference data in a male sample to categorise areal bone mineral density (BMD). Using male reference data, a large proportion of fractures arose from osteopenia, whereas using female reference data shifted the fracture burden into normal BMD. INTRODUCTION: The purpose of this study was to describe fracture risk associated with osteopenia and osteoporosis in older men, defined by areal BMD and using cut-points derived from male and female reference data. METHODS: As part of the Geelong Osteoporosis Study, we followed 619 men aged 60-93 years after BMD assessments (performed 2001-2006) until 2010, fracture, death or emigration. Post-baseline fractures were radiologically confirmed, and proportions of fractures in each BMD category were age-standardised to national profiles. RESULTS: Based on World Health Organization criteria, and using male reference data, 207 men had normal BMD at the femoral neck, 357 were osteopenic and 55 were osteoporotic. Using female reference data, corresponding numbers were 361, 227 and 31. During the study, 130 men died, 15 emigrated and 63 sustained at least one fracture. Using male reference data, most (86.5 %) of the fractures occurred in men without osteoporosis on BMD criteria (18.4 % normal BMD, 68.1 % osteopenia). The pattern differed when female reference data were used; while most fractures arose from men without osteoporosis (88.2 %), the burden shifted from those with osteopenia (34.8 %) to those with normal BMD (53.4 %). CONCLUSIONS: Decreasing BMD categories defined increasing risk of fracture. Although men with osteoporotic BMD were at greatest risk, they made a relatively small contribution to the total burden of fractures. Using male reference data, two-thirds of the fractures arose from men with osteopenia. However, using female reference data, approximately half of the fractures arose from those with normal BMD. Using female reference data to define osteoporosis in men does not appear to be the optimal approach.

Wind observations above an urban river using a new lidar technique, scintillometry and anemometry.

Airflow along rivers might provide a key mechanism for ventilation in cities: important for air quality and thermal comfort. Airflow varies in space and time in the vicinity of rivers. Consequently, there is limited utility in point measurements. Ground-based remote sensing offers the opportunity to study 3D airflow in locations which are difficult to observe with conventional approaches. For three months in the winter and spring of 2011, the airflow above the River Thames in central London was observed using a scanning Doppler lidar, a scintillometer and sonic anemometers. First, an inter-comparison showed that lidar-derived mean wind-speed estimates compare almost as well to sonic anemometers (root-mean-square error (rmse) 0.65-0.68 ms(-1)) as comparisons between sonic anemometers (0.35-0.73 ms(-1)). Second, the lidar duo-beam operating strategy provided horizontal transects of wind vectors (comparison with scintillometer rmse 1.12-1.63 ms(-1)) which revealed mean and turbulent airflow across the river and surrounds; in particular, channelled airflow along the river and changes in turbulence quantities consistent with the roughness changes between built and river environments. The results have important consequences for air quality and dispersion around urban rivers, especially given that many cities have high traffic rates on roads located on riverbanks.

Primary systemic vasculitis: clinical features and mortality.

BACKGROUND: Wegener's granulomatosis (WG), Churg Strauss syndrome (CSS) and microscopic polyangiitis (MPA) are primary systemic vasculitides (PSV), the clinical features of which have been described from tertiary centres. AIM: To provide the first clinical description of MPA from a general hospital and compare clinical features with WG and CSS. DESIGN: Retrospective analysis of patient records. METHODS: Records of 99 PSV patients attending a single hospital, from 1988 to 2000, were reviewed for: clinical features, date/age at diagnosis, sex, duration of illness, anti-neutrophil cytoplasmic antibodies (ANCA), treatment, comorbidity and deaths. Cases were classified using ACR, CHCC and Lanham criteria/definitions. Birmingham vasculitis activity scores (BVAS) and damage index (VDI) were calculated. Survival was assessed using Cox proportional hazards model and standardized mortality ratios (SMRs). RESULTS: Compared to previous reports there was more ENT (29%) and respiratory (29%) but less renal (92%) involvement in MPA, and less ENT involvement in WG (81%). CSS showed high neurological (72%), cardiovascular (28%) and gastrointestinal (17%) involvement and the highest median (range) VDI (p = 0.01 vs. WG; p = 0.001 vs. MPA). BVAS1 was significantly lower in MPA than in WG [median (range) 15 (4-29) vs. 21 (6-39), (p = 0.001)] but not in CSS [20 (7-28), p = 0.08]. SMR (95%CI) for PSV was 4.8 (3.0-6.6); 5-year survival was 45.1% for MPA, 75.9% for WG and 68.1% for CSS. Age was a significant risk, but only to the same extent as in the reference population. When age was adjusted for, no other significant factor was found. DISCUSSION: The clinical characteristics seen here are similar to those in previous series. There are difficulties in using the MPA CHCC definitions in classification. There is a high proportion of neurological involvement in CSS, causing permanent damage. MPA may have a poorer prognosis than WG or CSS.

Rheumatoid vasculitis: becoming extinct?

BACKGROUND: Systemic rheumatoid vasculitis (SRV) is a relatively rare complication of RA. The incidence of SRV appeared to increase during the 1970s and 1980s from 6.0 to 12.5/million. During the 1990s there have been major changes in the treatment of RA, with more aggressive control of inflammation. Our aim was to study the epidemiology of SRV in a stable, well-defined population over a 15-yr period. METHODS: Since 1988 we have maintained a prospective register of all patients with systemic vasculitis attending the Norfolk and Norwich University Hospital. Patients presenting with new-onset SRV, as defined by the criteria of Scott and Bacon, and registered with general practitioners in the former Norwich Health Authority area between 1988 and 2002 were identified. The population in 2002 was estimated to be 445 000 (215 000 males). RESULTS: Fifty-one patients (24 male) with SRV were identified, with median age 61 yr and disease duration 16.8 yr. The overall annual incidence was 7.9/million (95% CI 5.9-10.4) (males, 7.7/million; females, 8.1/million). During the first quinquennium (1988-92) the incidence was 11.6/million (95% CI 7.4-17.0) and during the third (1998-2002) it was 3.6/million (95% CI 1.6-7.1). A rolling 3-yr average showed that the peak incidence was in 1992-94, at 15.2/million (95% CI 9.1-23.8), and the nadir was in 1998-2000, at 3.0/million (95% CI 0.8-7.8). A similar pattern was seen for males and females. There was no difference in age or disease duration at onset of SRV between the three quinquennia. CONCLUSIONS: The incidence of SRV has declined dramatically since the 1980s. This could be due to better control of inflammatory disease or changes in smoking habits.

Evaluation of the Sørensen diagnostic criteria in the classification of systemic vasculitis.

OBJECTIVES: To evaluate the use of the diagnostic criteria for Wegener's granulomatosis (WG) and microscopic polyangiitis (mPA) proposed by Sørensen et al. in the classification of primary systemic vasculitis (PSV). METHODS: We applied to our cohort of PSV patients the American College of Rheumatology (ACR) criteria for WG, Churg-Strauss syndrome (CSS) and polyarteritis nodosa (PAN), the Chapel Hill Consensus Conference (CHCC) definitions for WG, mPA and CSS, the Hammersmith criteria for CSS and the Sørensen criteria for WG and mPA. RESULTS: Ninety-nine PSV cases were identified. Fifty-six fulfilled criteria for WG (ACR), 60 for PAN (ACR) and 15 for CSS (ACR). Four fulfilled the Hammersmith criteria for CSS. Thirty-nine were defined as mPA (CHCC). Fifty-three patients fulfilled the Sørensen criteria for WG and three for mPA. Five of six patients classified as WG (ACR) who did not meet the Sørensen criteria were excluded by eosinophilia. Six patients who did not fulfil WG (ACR) met the Sørensen criteria for WG. CONCLUSION: The classification of systemic vasculitis is complicated and many cases fulfil more than one set of criteria. The Sørensen criteria for WG is limited by its exclusion of eosinophilia despite reports of an association. We recommend that tissue eosinophilia or peripheral eosinophilia of <1.5x10(9)/l should not exclude a diagnosis of WG. With this modification, the Sørensen criteria for WG may be a useful method of classification, especially in confirming the classification of WG in patients who fulfil both WG (ACR) and mPA (CHCC). Few patients fulfilled the Sørensen criteria for mPA which suggests that they are not of value in classification.

A swollen leg unmasks longstanding SLE.

We report a case of long-standing SLE which presented with symptomatic muscle vasculitis on a background of photosensitivity, arthralgia and myalgia. The diagnosis was complicated by cardiomyopathy, nephrotic syndrome and diabetes. We highlight the benefits of aggressive treatment in severe disease and the importance of recognising and treating comorbidity especially ih relation to atherosclerosis.

Geoepidemiology of systemic vasculitis: comparison of the incidence in two regions of Europe.

OBJECTIVE: The aetiopathogenesis of the primary systemic vasculitides (PSV) is unknown but includes both environmental and genetic factors. The development of classification criteria/definitions for PSV allows comparison of the epidemiology between different regions. METHODS: The same methods and the American College of Rheumatology (1990) criteria or Chapel Hill definitions were used to compare the epidemiology of Wegener's granulomatosis, Churg-Strauss syndrome, microscopic polyangiitis, and polyarteritis nodosa in Norwich (east England population 413 500) and Lugo (northwest Spain population 204 100). Patients with PSV were identified between 1 January 1988 and 31 December 1998. RESULTS: Overall, the incidence of PSV in adults was almost equal in Norwich (18.9/million) and Spain (18.3/million). The incidence of Wegener's granulomatosis in Norwich (10.6/million) was greater than in Spain (4.9/million). There was a marked age-specific increase in incidence in Norwich with a peak age 65-74 years (52.9/million), but a virtually equal age distribution between ages 45 and 74 in Lugo (34.1/million). There was no significant increase with time in either population, or evidence of cyclical changes in incidence. CONCLUSION: These data support the suggestion that environmental factors may be important in the pathogenesis of PSV.

Epidemiology of systemic vasculitis: a ten-year study in the United Kingdom.

OBJECTIVE: To describe the epidemiology of the primary systemic vasculitides (PSV; Wegener's granulomatosis, Churg-Strauss syndrome, microscopic polyangiitis, polyarteritis nodosa) in a well-defined population over a 10-year period. METHODS: An inception cohort of patients from the Norwich Health Authority (NHA) who were >15 years of age and had PSV first diagnosed between January 1, 1988 and December 31, 1997 was collected. Incidence rates were adjusted for age and sex to the 1992 population. The prevalence of PSV in this cohort was estimated on December 31, 1997. Patients were classified according to the American College of Rheumatology 1990 vasculitis criteria and the Chapel Hill Consensus definitions. RESULTS: Eighty-two NHA residents fulfilled the inclusion criteria. There were 47 men and 35 women, with a mean age of 62.9 years (median 65.0 years). The overall annual incidence of PSV among NHA residents was 19.8/million (95% confidence interval [95% CI] 15.8-24.6). The point prevalence on December 31, 1997 was 144.5/million (95% CI 110.4-185.3). PSV was more common in males (23.5/million; 95% CI 17.3-31.3) than females (16.4/million; 95% CI 11.4-22.8). The age- and sex-specific incidence showed a clear increase with age, with an overall peak in the 65-74 year age group (60.1/million). CONCLUSION: In our study population, the annual incidence of PSV is slowly increasing with time and the incidence is greatest in the elderly.

Primary renal vasculitis in Norfolk--increasing incidence or increasing recognition?

BACKGROUND: The incidence of renal vasculitis has previously been estimated using histological definitions or only a single clinical diagnosis, e.g. Wegener's Granulomatosis (WG). Our hospital is the single referral centre for the former Norwich Health Authority (NHA) which encompasses a stable, homogeneous, well-defined and studied population. We estimated the overall incidence of primary renal vasculitis and the incidence within individual clinical disease classifications. METHODS: All cases of primary renal vasculitis diagnosed within the NHA over 66 months (1992-1997) were identified by review of renal biopsies, the Norfolk Vasculitis Register, hospital discharge summaries and plasmapheresis records. Patients were classified using the 1990 American College of Rheumatology criteria for Polyarteritis Nodosa (PAN), Churg Strauss Syndrome (CSS) and Henoch-Schonlein Purpura; the Chapel Hill Consensus Conference Definitions for Microscopic Polyangiitis (mPA) and the Lanham criteria for CSS. Incidence figures were calculated using the NHA adult population of 413747 (1994). Ninety-five per cent confidence intervals (C.I.) were calculated using the poisson distribution. RESULTS: The overall annual incidence for primary renal vasculitis was 18/million (C.I. 12.9-24.4). The annual incidence of renal involvement of individual diseases was as follows: WG 7.9/million (95% C.I. 4.7-12.5); mPA 7.5/million (95% C. I. 4.4-12.0); PAN 7.0/million (95% C.I. 4.0-11.4); HSP 3.1/million (95% C.I. 1.2-6.3); CSS 1.3/million (95% C.I. 0.3-3.9). CONCLUSIONS: The annual incidence for primary renal vasculitis overall and the individual subtypes in Norfolk is much higher than previous European estimates. This may reflect an increasing incidence in primary renal vasculitis with time or underestimation in previous studies. However the incidence of renal vasculitis in our population is markedly lower than reported in Kuwait. There may therefore be true variation in incidence between populations which could have implications for the aetiology of primary vasculitis.

Lessons from atypical groin pain: presentation and treatment of a schwannoma.

A 16-year-old boy presented with pain in the right knee, groin, and hip after a touch football game. He was initially diagnosed as having a medial collateral ligament sprain of the right knee and an adductor muscle strain. Despite standard conservative therapy, he had persistent hip pain and migratory pain to the right lower abdomen and flank. A bone scan and abdominal CT scan were negative, but MRI revealed a mass in the cauda equina at L3-4, confirmed with myelography. A benign schwannoma was surgically excised without neurologic sequelae. The patient resumed daily activities 5 weeks after surgery.

A silicone splint for auricular hematoma.

Auricular hematomas are often encountered in a sports medicine practice, most commonly among wrestlers, but also in boxers, football and rugby players, and judo athletes.(1) A relatively new treatment, the use of a silicone splint, offers several advantages over other treatments with regard to the risk of recurrence, observation of the site, and return to competition.

Routine perioperative dipyridamole 201Tl imaging in diabetic patients undergoing vascular surgery.

OBJECTIVE: To assess the utility of dipyridamole thallium testing in symptomatic and asymptomatic patients with diabetes undergoing vascular surgery. RESEARCH DESIGN AND METHODS: Dipyridamole 201Tl myocardial scintigraphy was performed preoperatively in 93 consecutive patients with diabetes undergoing peripheral vascular procedures. The utility of clinical and thallium variables in predicting cardiovascular complications was assessed. RESULTS: Two groups of patients were identified: group A (36 patients) without clinical evidence of cardiac disease and group B (57 patients) with clinical evidence of cardiac disease. Dipyridamole thallium scans were abnormal in 21 of 36 (58%) of group A patients compared with 53 of 57 (93%) of group B patients (P < 0.0001). Compared with group B patients with perfusion defects, group A patients with perfusion abnormalities tended to have fewer defects per scan (2.7 +/- 1.5 vs. 3.6 +/- 1.9, P = 0.05). No perioperative cardiac complications occurred in group A patients while perioperative cardiac complications occurred in 9 of 57 (16%, 95% CI 7-28%) group B patients (P = 0.01). For the entire study population, the complication rate was 10%. CONCLUSIONS: Diabetic individuals without clinical markers for coronary artery disease appear to be at low risk for adverse postoperative cardiac events after vascular surgery. Preoperative myocardial perfusion imaging may add little to cardiovascular risk assessment in this subgroup of patients with diabetes.

Silent myocardial ischemia and infarction in diabetics with peripheral vascular disease: assessment by dipyridamole thallium-201 scintigraphy.

We investigated the incidence of silent myocardial ischemia and infarction as assessed by dipyridamole thallium scintigraphy in 30 diabetic patients with peripheral vascular disease and without clinical suspicion of coronary artery disease. Seventeen patients (57%) had thallium abnormalities, with reversible thallium defects compatible with ischemia in 14 patients (47%) and evidence of prior, clinically silent myocardial infarction in 11 patients (37%). Thallium abnormalities were most frequent in patients with concomitant hypertension and cigarette smoking (p = 0.001). These results suggest that unsuspected coronary artery disease is common in this particular group of patients with diabetes mellitus.

Severe Ankle Sprains.

In brief Severe (grade 3) ankle sprains with lateral ligament disruption are common in both athletes and nonathletes. Inadequate treatment leads to chronic ankle instability. Twenty-six patients underwent a 3-week treatment program using an ankle-foot orthosis (AFO), followed by a 4-week rehabilitation program. Of these patients, 96% returned to activity without restriction in about 2 1/2 months. Advantages of the AFO include ease of application, patient comfort and convenience, early ambulation, access for therapy, and rapid return to sports with a stable, asymptomatic ankle.

Predictive value of quantitative dipyridamole-thallium scintigraphy in assessing cardiovascular risk after vascular surgery in diabetes mellitus.

Cardiac complications represent a major risk to patients undergoing vascular surgery. Diabetic patients may be particularly prone to such complications due to the high incidence of concomitant coronary artery disease, the severity of which may be clinically unrecognized. Attempts to stratify groups by clinical criteria have been useful but lack the predictive value of currently used noninvasive techniques such as dipyridamole-thallium scintigraphy. One hundred one diabetic patients were evaluated with dipyridamole-thallium scintigraphy before undergoing vascular surgery. The incidence of thallium abnormalities was high (80%) and did not correlate with clinical markers of coronary disease. Even in a subgroup of patients with no overt clinical evidence of underlying heart disease, thallium abnormalities were present in 59%. Cardiovascular complications, however, occurred in only 11% of all patients. Statistically significant prediction of risk was not achieved with simple assessment of thallium results as normal or abnormal. Quantification of total number of reversible defects, as well as assessment of ischemia in the distribution of the left anterior descending coronary artery was required for optimum predictive accuracy. The prevalence of dipyridamole-thallium abnormalities in a diabetic population is much higher than that reported in nondiabetic patients and cannot be predicted by usual clinical indicators of heart disease. In addition, cardiovascular risk of vascular surgery can be optimally assessed by quantitative analysis of dipyridamole-thallium scintigraphy and identification of high- and low-risk subgroups.

Alcohol-mediated effects on the level of cytochrome P-450 and heme biosynthesis in cultured rat hepatocytes.

Interaction of alcohol and drugs in the liver appears to involve common microsomal oxidative enzymes which utilize cytochrome P-450. Since alcohol augments the toxicity of a variety of drugs, the regulation of the P-450 hemoprotein, a primary component in hepatic drug metabolizing systems, may play a vital role in this phenomenon. We utilize an adult rat liver culture system as a model to explore the action of levels of alcohol below that which is necessary to produce intoxication in humans. The addition of 16 mM ethanol (70 mg/dl) to these hepatocytes results in a 49.5% decrease in cytochrome P-450 activity after 24 h, and a 3-fold increase in the activity of delta-aminolevulinate synthase, the rate-limiting enzyme in hepatic heme biosynthesis. Furthermore, ethanol treatment also causes a transient decrease in the level of intracellular heme. However, the diminished level of total heme does not appear to act as a repressor for delta-aminolevulinate synthase, since it occurs after the initial stimulation of the enzyme by ethanol.

Inhibition of steroid-mediated induction of delta-aminolevulinic acid synthase by 2-diethylaminoethyl-2,2-diphenylvalerate HCl (SKF 525-A).

The inhibition of the steroid-mediated induction of delta-aminolevulinate synthase, the rate-limiting enzyme in hepatic porphyrin-heme biosynthesis, by 2-diethylaminoethyl-2,2-diphenylvalerate HCl (SKF 525-A) as studied in cultured chick embryo liver cells. The formation of porphyrins in response to cyproterone, a synthetic steroid, was inhibited in a time-dependent manner by SKF 525-A, an inhibitor of several drug metabolizing enzyme systems. This action is a result of an inhibitory effect of SKF 525-A on the cyproterone-mediated induction of delta-aminolevulinate synthase; SKF 525-A also inhibited the induction of the enzyme by the naturally occurring 5 beta-H steroids, etiocholanolone and pregnanolone. Employing [3H]etiocholanolone, we provide evidence that this inhibition is not associated with either decreased uptake or an altered metabolism of the steroid. Moreover, approx 4-6-fold more radioactivity was associated with [3H]etiocholanolone-treated cells cultured in the presence of SKF 525-A. Alternative mechanisms for the induction of delta-aminolevulinate synthase by steroids are proposed which do not require the interaction of steroid-receptor complex with the genome.