Incidence of venous thromboembolism after elective knee arthroscopic surgery: a historical cohort study.

BACKGROUND: The incidence of symptomatic venous thromboembolism (VTE) after knee arthroscopy is uncertain. OBJECTIVES: To estimate the incidence of symptomatic VTE after arthroscopic knee surgery. METHODS: In a population-based historical cohort study, all Olmsted County, MN, USA, residents undergoing a first arthroscopic knee surgery during the 18-year period of 1988-2005 were followed for incident deep venous thrombosis or pulmonary embolism. The cumulative incidence of VTE after knee arthroscopy was determined using the Kaplan-Meier product limit estimator. Patient age at surgery, sex, calendar year of surgery, body mass index, anesthesia characteristics, and hospitalization were tested as potential predictors of VTE using Cox proportional hazards modeling, both univariately and adjusted for age and sex. RESULTS: Among 4833 Olmsted County residents with knee arthroscopy, 18 developed postoperative VTE, all within the first 6 weeks after surgery. The cumulative incidence rates of symptomatic VTE at 7, 14, and 35 days were 0.2%, 0.3%, and 0.4%, respectively. The hazard for postoperative VTE was significantly increased for older patient age (hazard ratio = 1.34 for each 10-year increase in patient age; P = 0.03) and hospitalization either before or after knee arthroscopy (hazard ratio = 14.1; P < 0.001). CONCLUSIONS: The incidence of symptomatic VTE after arthroscopic knee surgery is very low. Older age and hospitalization are associated with increased risk. Routine prophylaxis to prevent symptomatic VTE is likely not needed in this patient population.

A genome-wide association study of venous thromboembolism identifies risk variants in chromosomes 1q24.2 and 9q.

OBJECTIVES: To identify venous thromboembolism (VTE) disease-susceptibility genes. PATIENTS AND METHODS: We performed in silico genome wide association scan (GWAS) analyses using genotype data imputed to approximately 2.5 million single-nucleotide polymorphisms (SNPs) from adults with objectively-diagnosed VTE (n=1503), and controls frequency matched on age and gender (n=1459; discovery population). Single-nucleotide polymorphisms exceeding genome-wide significance were replicated in a separate population (VTE cases, n=1407; controls, n=1418). Genes associated with VTE were re-sequenced. RESULTS: Seven SNPs exceeded genome-wide significance (P<5×10(-8)): four on chromosome 1q24.2 (F5 rs6025 [factor V Leiden], BLZF1 rs7538157, NME7 rs16861990 and SLC19A2 rs2038024) and three on chromosome 9q34.2 (ABO rs2519093 [ABO intron 1], rs495828, rs8176719 [ABO blood type O allele]). The replication study confirmed a significant association of F5, NME7 and ABO with VTE. However, F5 was the main signal on 1q24.2 as only ABO SNPs remained significantly associated with VTE after adjusting for F5 rs6025. This 1q24.2 region was shown to be inherited as a haplotype block. ABO re-sequencing identified 15 novel single nucleotide variations (SNV) in ABO intron 6 and the ABO 3' UTR that were strongly associated with VTE (P<10(-4)) and belonged to three distinct linkage disequilibrium (LD) blocks; none were in LD with ABO rs8176719 or rs2519093. Our sample size provided 80% power to detect odds ratios (ORs)=2.0 and 1.51 for minor allele frequencies=0.05 and 0.5, respectively (α=1×10(-8); 1% VTE prevalence). CONCLUSIONS: Apart from F5 rs6025, ABO rs8176719, rs2519093 and F2 rs1799963, additional common and high VTE-risk SNPs among whites are unlikely.

Mucositis, conjunctivitis but no rash - the "Atypical Stevens - Johnson syndrome".

The Stevens-Johnson syndrome (SJS) classically involves a rash, conjunctivitis and mucositis. We describe the case of a young adult male with isolated mucositis and conjunctivitis . Previous rare reports of severe SJS like syndromes without a rash are confined to children, usually with mycoplasma pnemoniae infection.(1) Terminology for this syndrome includes - "Stevens-Johnson Syndrome without skin lesions", or "Atypical Stevens - Johnson Syndrome".(2) This case highlights the importance of maintaining an open mind when a "full house" of clinical features is absent. It also illustrates the use of a rapid electronic literature review as a clinical tool. The importance of updating records when a drug has been cleared of causing harm is highlighted.

Genetic variation within the anticoagulant, procoagulant, fibrinolytic and innate immunity pathways as risk factors for venous thromboembolism.

BACKGROUND: Venous thromboembolism (VTE) is highly heritable (estimated heritability [h(2)]=0.62) and likely to be a result of multigenic action. OBJECTIVE: To systematically test variation within genes encoding for important components of the anticoagulant, procoagulant, fibrinolytic and innate immunity pathways for an independent association with VTE. METHODS: Non-Hispanic adults of European ancestry with objectively-diagnosed VTE, and age- and sex- matched controls, were genotyped for 13 031 single nucleotide polymorphisms (SNPs) within 764 genes. Analyses (n=12296 SNPs) were performed with plink using an additive genetic model and adjusted for age, sex, state of residence, and myocardial infarction or stroke. RESULTS: Among 2927 individuals, one or more SNPs within ABO, F2, F5, F11, KLKB1, SELP and SCUBE1 were significantly associated with VTE, including factor (F) V Leiden, prothrombin G20210A, ABO non-O blood type, and a novel association with ABO rs2519093 (OR=1.68, P-value=8.08×10(-16) ) that was independent of blood type. In stratified analyses, SNPs in the following genes were significantly associated with VTE: F5 and ABO among both genders and LY86 among women; F2, ABO and KLKB1 among FV Leiden non-carriers; F5, F11, KLKB1 and GFRA1 in those with ABO non-O blood type; and ABO, F5, F11, KLKB1, SCUBE1 and SELP among prothrombin G20210A non-carriers. The ABO rs2519093 population-attributable risk (PAR) exceeded that of FV Leiden and prothrombin G20210A, and the joint PAR of FV Leiden, prothrombin G20210A, ABO non-O and ABO rs2519093 was 0.40. CONCLUSIONS: Anticoagulant, procoagulant, fibrinolytic and innate immunity pathway genetic variation accounts for a large proportion of VTE among non-Hispanic adults of European ancestry.

Lead Poisoning presenting as acute severe myalgia: Why was the diagnosis delayed and what lessons can we learn as acute physicians?

Patients presenting to the "front door" with acute neuromuscular symptoms are challenging. Toxins need consideration as possible causative agents if there is the possibility of relevant exposure. This requires a thorough history1 and an awareness of local ethnic, social and industrial cultures within the practice locality. We describe a case of lead poisoning in a 35 year old man who presented with severe, progressive, myalgia. We consider that basic errors in clinical processing delayed a potentially difficult and serious diagnosis and these are discussed. The importance of maintaining a thorough initial clerking process within the Acute Medical Unit is highlighted. This should include a comprehensive occupational history. Acute physicians should familiarize themselves with local industry and the toxic syndromes they can produce.

Outcome following unrelated cord blood transplant in 136 patients with malignant and non-malignant diseases: a report from the Australian and New Zealand children's haematology and oncology group.

Unrelated umbilical cord blood (UCB) is an alternative stem cell source for paediatric patients lacking a matched related or unrelated marrow donor. We report the results of all paediatric unrelated UCB transplants performed in Australia and New Zealand over a 10-year period. A total of 135 patients were transplanted, 100 for malignant disease (74%) and 35 for non-malignant disorders. The majority (88%) of patients received an HLA-mismatched graft. The median infused total nucleated cell dose was 4.7 x 10(7)/kg and CD34+ count 1.9 x 10(5)/kg. Neutrophil engraftment occurred in 83% of patients by day 42 (median 23 days) and platelet engraftment in 55% by day 60 (median 56 days). Grades II-IV and III-IV acute GVHD occurred in 41 and 18% of patients, respectively. TRM and overall survival 1-year post transplant were 32 and 61%, respectively. A higher probability of neutrophil recovery (P=0.004) and faster time to recovery (median 18 days vs 26 days, P=0.008) were observed in recipients of a cord unit with a CD34 cell dose >or=1.7 x 10(5)/kg. Our results support selection of cord units with CD34 cell doses >or=1.7 x 10(5)/kg to promote faster engraftment, improve survival and lower TRM.

Familial segregation of venous thromboembolism.

BACKGROUND: Venous thromboembolism (VTE) is postulated as a complex disease, but the heritability and mode of inheritance are uncertain. OBJECTIVE: To determine if VTE (i) segregates in families; (ii) is attributable to inheritance, shared environment, or both; and (iii) the possible mode of inheritance. PATIENTS AND METHODS: In a family-based study of relatives from 751 probands (60% female) with objectively diagnosed VTE (without cancer), we performed complex segregation analyses corrected for mode of ascertainment, considering age-specific, non-gender- and gender-specific liability classes under Mendelian and non-Mendelian assumptions. We tested 12 models categorized into four model sets: (i) sporadic (assumes no genetic effect); (ii) Mendelian inheritance of a major gene (including dominant, additive, recessive or codominant classes); (iii) mixed model (Mendelian inheritance including the same four classes plus the effect of polygenes); and (iv) non-Mendelian. RESULTS: Among the 16 650 relatives, 753 (48% female) were affected with VTE, of whom 62% were first-degree relatives. The sporadic model was rejected in both non-gender- and gender-specific liability class analyses. Among the remaining gender-specific models, the unrestricted (non-Mendelian) inheritance model was favored with an estimated heritability of 0.52. Among the Mendelian models, the dominant mixed model was preferred, with an estimated heritability and major disease allele frequency of 0.62 and 0.25, respectively, suggesting an effect of several minor genes. CONCLUSION: A multifactorial non-Mendelian inheritance model was favored as the cause for VTE, while a model postulating a purely environmental cause was rejected. VTE is probably a result of multigenic action as well as environmental exposures.

Incidence of venous thromboembolism in hospitalized patients vs community residents.

OBJECTIVE: To estimate the incidence rates of deep venous thrombosis (DVT) and pulmonary embolism (PE) in hospitalized patients and to compare these with incidence rates in community residents. PATIENTS AND METHODS: We performed a retrospective review of the complete medical records from a population-based inception cohort of patients who resided in Olmsted County, Minnesota, and had an incident DVT or PE from 1980 through 1990. RESULTS: From 1980 through 1990, 911 Olmsted County residents experienced their first lifetime event of definite, probable, or possible venous thromboembolism. Of these residents, 253 had been hospitalized for some reason other than a diagnosis of DVT or PE (in-hospital cases), and 658 were not hospitalized at onset of venous thromboembolism (community residents). The average annual age- and sex-adjusted incidence of in-hospital venous thromboembolism was 960.5 (95% confidence interval, 795.1-1125.9) per 10,000 person-years and was more than 100 times greater than the incidence among community residents at 7.1 (95% confidence interval, 6.5-7.6) per 10,000 person-years. The incidence of venous thromboembolism rose markedly with increasing age for both groups, with PE accounting for most of the age-related increase among in-hospital cases. Incidence rates in the 2 groups changed little over time despite a reduction in the average length of hospital stay between 1980 and 1990. CONCLUSIONS: Venous thromboembolism is a major national health problem, especially among elderly hospitalized patients. This finding emphasizes the need for accurate identification of hospitalized patients at risk for venous thromboembolism and a better understanding of the mechanisms involved so that safe and effective prophylaxis can be implemented.

Fat-soluble vitamin levels in patients with primary biliary cirrhosis.

OBJECTIVE: To determine the occurrence of fat-soluble vitamin deficiencies and to identify clinical factors that may predict vitamin deficiency in patients with primary biliary cirrhosis (PBC). METHODS: Review of our data from a randomized, placebo-controlled trial that evaluated the efficacy of UDCA in 180 patients with PBC. We use the first available measurements of vitamin levels in each study participant. Vitamin levels for A, D, and E were measured in serum. The prothrombin time (PT) was used as a surrogate marker for vitamin K. RESULTS: The proportion of patients with fat-soluble vitamin deficiencies in the treatment and placebo groups was similar and the data sets were combined. The proportion with vitamin A, D, E or K deficiency was 33.5%, 13.2%, 1.9%, and 7.8%, respectively. In multivariate analysis, the Mayo risk score, advanced histological stage, and total cholesterol were independently associated with vitamin A deficiency whereas serum albumin levels was independently associated with vitamin D deficiency. No factors were associated with vitamin E or K deficiency in multivariate analysis owing to the few vitamin E and K deficient patients. Factors predictive of vitamin K deficiency by univariate analysis included Mayo risk score, advanced histological stage, HDL, total bilirubin, AST, and albumin. The cut-off value of the Mayo risk score with the highest sensitivity and specificity for vitamin A deficiency was 5.0. CONCLUSION: Other than deficiency of vitamin A, deficiency of fat-soluble vitamins occurs uncommonly in patients with PBC. A Mayo risk score > or = 5 helps in selecting patients with PBC for surveillance for vitamin A deficiency.

A prospective cohort study of practice guidelines in inflammatory bowel disease.

OBJECTIVES: Practice guidelines should improve care, but they are not routinely followed, in part because of lack of proven benefit. We evaluated the effect of introducing guidelines for inflammatory bowel disease (IBD) on practice variation and the IBD Quality of Life (IBDQ) score. METHODS: This was a prospective, controlled, cohort study. A total of 65 patients were matched according to month of visit, diagnosis, and disease activity with control subjects seen 1 yr earlier. Physicians were educated throughout the study regarding the guidelines. Variation was measured by the Mayo Practice Guideline Score (MPGS), a 15-point assessment of documentation of diagnosis, nutrition, social support, education, functional status, and treatment. The IBDQ was measured at baseline and at 1 yr in the intervention group and after 1 yr in the control group. RESULTS: The MPGS was significantly higher in the intervention group compared to the controls (p = 0.002), with median values of 12 versus 11. The IBDQ median score increased significantly in the intervention group (p < 0.001), baseline median of 133 versus 15-month median of 184. However, the final IBDQ was not significantly higher in the intervention group than in the controls (p = 0.33). CONCLUSIONS: Practice guidelines for IBD reduce practice variation. The quality of life improved significantly compared to baseline with practice guidelines, but not compared to controls, perhaps because of the small sample size and homogenous practice setting. The MPGS is a tool that can be used in day-to-day management of IBD patients.

The epidemiology of venous thromboembolism in the community.

The incidence of venous thromboembolism exceeds 1 per 1000; over 200,000 new cases occur in the United States annually. Of these, 30% die within 30 days; one-fifth suffer sudden death due to pulmonary embolism. Despite improved prophylaxis, the incidence of venous thromboembolism has been constant since 1980. Independent risk factors for venous thromboembolism include increasing age, male gender, surgery, trauma, hospital or nursing home confinement, malignancy, neurologic disease with extremity paresis, central venous catheter/transvenous pacemaker, prior superficial vein thrombosis, and varicose veins; among women, risk factors include pregnancy, oral contraceptives, and hormone replacement therapy. About 30% of surviving cases develop recurrent venous thromboembolism within ten years. Independent predictors for recurrence include increasing age, obesity, malignant neoplasm, and extremity paresis. About 28% of cases develop venous stasis syndrome within 20 years. To reduce venous thromboembolism incidence, improve survival, and prevent recurrence and complications, patients with these characteristics should receive appropriate prophylaxis.

A randomized trial of intravenous immunoglobulin in inflammatory demyelinating optic neuritis.

OBJECTIVE: To determine whether IV immunoglobulin (IVIg) reverses chronic visual impairment in MS patients with optic neuritis (ON). METHODS: In this double-blind, placebo-controlled Phase II trial, 55 patients with persistent acuity loss after ON were randomized to receive either IVIg 0.4 g/kg daily for 5 days followed by three single infusions monthly for 3 months, or placebo. RESULTS: The trial was terminated by the National Eye Institute because of negative results when 55 of the planned 60 patients had been enrolled. Fifty-two patients completed the scheduled infusions, and 53 patients completed 12 months of follow-up. Analysis of this data indicated that a difference between treatment groups was not observed for the primary outcome measure, improvement in logMAR visual scores at 6 months (p = 0.766). Exploratory secondary analyses suggested that IVIg treatment was associated with improvement in visual function (including logMAR visual scores at 6 months and visual fields at 6 and 12 months) in patients with clinically stable MS during the trial. CONCLUSIONS: IVIg administration does not reverse persistent visual loss from ON to a degree that merits general use.

Trends in the incidence of venous stasis syndrome and venous ulcer: a 25-year population-based study.

BACKGROUND: The incidence rates of venous stasis syndrome and venous ulcer are uncertain, and trends in incidence are unknown. METHODS: We performed a retrospective review of the complete (inpatient and outpatient) medical records of a community population (Olmsted County, Minnesota) to estimate the incidence of venous stasis syndrome and venous ulcer during the 25-year period, 1966 to 1990, and to describe trends in incidence. RESULTS: A total of 1131 patients received a first lifetime diagnosis of venous stasis syndrome. A total of 263 patients received a first lifetime diagnosis of venous ulcer. The overall incidence of venous stasis syndrome and venous ulcer were 76.1 and 18.0 per 100,000 person-years, respectively. The incidence of both was higher in women than in men (83.7 vs 67.4 per 100,000 person-years for venous stasis syndrome; 20.4 vs 14.6 per 100,000 for venous ulcer) and increased with age for both sexes. There was no clear trend in the incidence of venous stasis syndrome over the 25-year period. Compared with 1966 to 1970, the incidence of venous ulcer decreased in 1971 to 1980, but was unchanged after 1981. Among 945 patients with venous stasis only, 60 subsequently had a venous ulcer. The average (+/- SD) time from venous stasis diagnosis to development of a venous ulcer was 5.0 (+/- 5.0) years. CONCLUSION: Venous stasis syndrome and venous ulcer are common, especially in the elderly population. The incidence of venous stasis syndrome has not changed since 1966, and venous ulcer incidence is unchanged since 1981. More accurate identification of patients at risk for venous stasis syndrome and venous ulcer and more effective prevention are needed.

Extent of high-grade dysplasia in Barrett's esophagus correlates with risk of adenocarcinoma.

BACKGROUND & AIMS: The identification of any high-grade dysplasia (HGD) in Barrett's esophagus has been considered to be an indication for esophagectomy because of the increased risk of cancer. The aim of this study was to determine if a limited extent of HGD has the same potential for cancer as diffuse HGD. METHODS: A retrospective cohort study was performed to assess the risk of developing adenocarcinoma in relationship to the extent of HGD found on endoscopic surveillance. The extent of HGD was defined as focal if cytologic and/or architectural changes of HGD were limited to a single focus of 5 or fewer crypts and diffuse if more than 5 crypts were involved in a single biopsy specimen or if HGD involved more than one biopsy fragment. The relative risk of cancer was assessed using a Cox proportional hazard model, and cancer-free survival was determined using survival curves. RESULTS: Sixty-seven patients with diffuse HGD and 33 with focal HGD satisfied selection criteria. Cancer-free survival rates at 1 and 3 years were 93% and 86% for focal HGD compared with 62% and 44% for diffuse HGD (P < 0.001). On univariate analysis, extent of HGD (relative risk, 5.36; 95% confidence interval, 1.84-15.56), nodularity on endoscopy (relative risk, 3.98; 95% confidence interval, 1.97-8.04), and lack of acid suppression (relative risk, 2.48; 95% confidence interval, 1.16-5.28) were associated with an increased risk of esophageal adenocarcinoma. Diffuse HGD had a 3.7-fold increase in the risk of esophageal cancer compared with focal HGD (P = 0.02) on multivariate analysis. CONCLUSIONS: Patients with focal HGD are less likely to have cancer during the first year after diagnosis or on subsequent follow-up compared with diffuse HGD.

Association of atrial fibrillation and aortic atherosclerosis: a population-based study.

OBJECTIVE: To examine the association between atrial fibrillation (AF) and aortic atherosclerosis in the general population. SUBJECTS AND METHODS: Transesophageal echocardiography was performed in 581 subjects, a random sample of the adult Olmsted County, Minnesota, population (45 years of age or older) participating in the Stroke Prevention: Assessment of Risk in a Community (SPARC) study. The frequency of aortic atherosclerosis was determined in 42 subjects with AF and compared with that in 539 subjects without AF (non-AF group). RESULTS: Subjects with AF were significantly older than non-AF subjects (mean +/- SD age, 82+/-10 vs 66+/-13 years, respectively; P<.001) and more commonly had hypertension (28 [66.7%] vs 288 [53.4%], respectively; P=.10). The 2 groups were similar in sex and frequency of diabetes mellitus, hyperlipidemia, or smoking history (P>.10). The odds of aortic atherosclerosis (of any degree) were 2.87 times greater (95% confidence interval [CI], 1.41-5.83; P=.004) and the odds of complex atherosclerosis (protruding atheroma >4 mm thick, mobile debris, or plaque ulceration) were 2.71 times greater (CI, 1.13-6.53; P=.03) in the AF group than in the non-AF group. Age was a significant predictor of aortic atherosclerosis (P<.001). After adjusting for age, the odds of atherosclerosis and complex atherosclerosis were not significantly different between the 2 groups (P=.13 and P=.75, respectively). CONCLUSIONS: In the general population, AF is associated with aortic atherosclerosis, including complex atherosclerosis. This association is related to age since both AF and aortic atherosclerosis are more frequent in the elderly population.

Risk factors for deep vein thrombosis and pulmonary embolism during pregnancy or post partum: a population-based, case-control study.

OBJECTIVE: We sought to determine risk factors for deep vein thrombosis and pulmonary embolism during pregnancy or post partum. STUDY DESIGN: We performed a population-based case-control study. All Olmsted County, Minnesota, residents with a first lifetime deep vein thrombosis or pulmonary embolism during pregnancy or post partum from 1966 to 1990 were identified (N = 90). Where possible, a resident without deep vein thrombosis or pulmonary embolism was matched to each patient by date of the first live birth after the patient's child. The medical records of all remaining patients and all control subjects were reviewed for >25 baseline characteristics, which were tested as risk factors for deep vein thrombosis or pulmonary embolism. RESULTS: In multivariate analysis smoking (odds ratio, 2.4) and prior superficial vein thrombosis (odds ratio, 9.4) were independent risk factors for deep vein thrombosis or pulmonary thrombosis during pregnancy or post partum. CONCLUSION: Venous thromboembolism prophylaxis may be warranted for pregnant women with prior superficial vein thrombosis. Smoking cessation should be recommended, especially during pregnancy and the postpartum period.

The venous stasis syndrome after deep venous thrombosis or pulmonary embolism: a population-based study.

OBJECTIVES: To estimate the incidence and determine predictors of venous stasis syndrome and venous ulcers after deep venous thrombosis and pulmonary embolism. PATIENTS AND METHODS: This population-based retrospective cohort study reviewed medical records of 1527 patients with incident deep venous thrombosis or pulmonary embolism between 1966 and 1990. We recorded baseline characteristics, event type (deep venous thrombosis with or without pulmonary embolism or pulmonary embolism alone), leg side and site of deep venous thrombosis (proximal with or without distal deep venous thrombosis vs distal deep venous thrombosis alone), and venous stasis syndrome and venous ulcer. RESULTS: Two hundred forty-five patients developed venous stasis syndrome. One-year, 5-year, 10-year, and 20-year cumulative incidence rates were 7.3%, 14.3%, 19.7%, and 26.8%, respectively. By 20 years the cumulative incidence of venous ulcers was 3.7%. Patients with deep venous thrombosis with or without pulmonary embolism were 2.4-fold (95% confidence interval, 1.7-fold-3.2-fold) more likely to develop venous stasis syndrome than patients with pulmonary embolism and no diagnosed deep venous thrombosis. In patients aged 40 years or younger with proximal compared with distal-only deep venous thrombosis, venous stasis syndrome was 3.0-fold more likely (95% confidence interval, 1.6-fold-4.7-fold). In patients with unilateral leg deep venous thrombosis, venous stasis syndrome usually developed in the concordant leg (P < .001). There was a 30% (95% confidence interval, 2%-62%) increased risk for venous ulcer per decade of age at the incident venous thromboembolism. CONCLUSIONS: The cumulative incidence of venous stasis syndrome continues to increase for 20 years after venous thromboembolism. Pulmonary embolism alone is less likely to cause venous stasis syndrome.

IV immunoglobulin does not reverse established weakness in MS.

BACKGROUND: Immunoglobulin (Ig) administration induces remyelination in the Theiler's virus model of MS. METHODS: A randomized, double-blinded, placebo-controlled trial of IV immunoglobulin (IVIg) was performed in patients with MS who had persistent muscle weakness that had been stable for between 4 and 18 months to determine whether this would improve muscle strength (primary outcome: isometric muscle strength). Patients received either IVIg (0.4 g/kg) or placebo daily for 5 days, then single infusions every 2 weeks for 3 months (total, 11 infusions). Muscle groups identified by clinical measures to have unchanging significant weakness were the major targets for therapeutic response (targeted neurologic deficit [TND]). RESULTS: IVIg was well tolerated. An interim analysis after 67 patients were enrolled indicated no difference in the degree of change in strength between treatment groups in either the TND or non-TND muscle groups at 6 months, and the trial was terminated. There was no apparent benefit in relapse behavior or impairment measures during the 6-month observation period. Nor was there apparent benefit in either patients who remained clinically stable or in those with evidence of disease activity. Patients with active MS during the trial worsened in both TND and non-TND muscle groups. This worsening was seen regardless of whether the clinical manifestations of disease activity involved the TND muscle groups. CONCLUSIONS: IVIg does not reverse established weakness in MS. Measurements of isometric muscle strength were reliable (reproducible) indices of strength and may be sensitive, objective methods to document functional changes in impairment in future MS trials.

Left atrial appendage flow velocities in subjects with normal left ventricular function.

The objectives of this study were to establish reference values and define the determinants of left atrial appendage (LAA) flow velocities in the general population. LAA flow velocities (contraction and filling velocities) were assessed by transesophageal echocardiography in 310 subjects aged > or = 45 years, sampled from the population-based Stroke Prevention: Assessment of Risk in a Community study. All subjects were in sinus rhythm, with preserved left ventricular systolic function (ejection fraction > or = 50%), and without valvular disease. Values of LAA contraction and filling velocities were established for various age groups in the population. Age was negatively associated with LAA contraction and filling velocities, which decreased by 4.1 cm/s (p < 0.001) and 2.0 cm/s (p < 0.01) for every 10 years of age, respectively. Contraction velocities were 5 cm/s higher in men than in women (p < 0.05). After adjusting for age and sex, heart rate was independently associated with LAA contraction velocities (p < 0.001; nonlinear association). Body surface area, left atrial size, left ventricular mass index, and a history of previous cardiac disease or hypertension showed no significant association with LAA flow velocities (p > 0.05). Furthermore, detailed analysis of 24-hour ambulatory blood pressure data (available in 253 subjects) showed no association between various blood pressure parameters (systolic and diastolic blood pressure, out-of-bed and in-bed measurements) and LAA flow velocities (all p > 0.05). In summary, the present study establishes the reference values for LAA flow velocities in a large sample of the general population. LAA flow velocities progressively decline with age in subjects with preserved left ventricular systolic function.

Independent association of high blood pressure and aortic atherosclerosis: A population-based study.

BACKGROUND: Atherosclerosis of the thoracic aorta is associated with stroke. The association between hypertension, a major risk factor for stroke, and aortic atherosclerosis has not been determined in the general population. METHODS AND RESULTS: Transesophageal echocardiography was performed in 581 subjects, a random sample of the Olmsted County (Minnesota) population aged >/=45 years participating in the Stroke Prevention: Assessment of Risk in a Community (SPARC) study. Blood pressure was assessed by multiple office measurements and 24-hour ambulatory blood pressure monitoring. The association between blood pressure variables and aortic atherosclerosis was evaluated by multiple logistic regression, adjusting for other associated variables. Among subjects with atherosclerosis, blood pressure variables associated with complex aortic atherosclerosis (protruding plaques >/=4 mm thick, mobile debris, or ulceration) were determined. Age and smoking history were independently associated with aortic atherosclerosis of any degree (P: