Exploring the Lipid Paradox Theory in Rheumatoid Arthritis: Associations of Low Circulating Low-Density Lipoprotein Concentration With Subclinical Coronary Atherosclerosis.

OBJECTIVE: Rheumatoid arthritis (RA) patients with the lowest circulating low-density lipoprotein (LDL) concentrations are at heightened risk of cardiovascular events. However, the atherosclerosis burden within this subgroup is unknown. METHODS: RA patients pooled from 4 cohort studies of cardiovascular disease (CVD; n = 546) were compared with non-RA controls from the Multi-Ethnic Study of Atherosclerosis (n = 5,279). Those taking lipid-lowering medications were excluded. Differences in cardiac computed tomography-derived Agatston coronary artery calcium (CAC) scores between the RA and control groups were compared across strata of LDL concentration. RESULTS: Among those with low LDL concentrations (<70 mg/dl), mean adjusted CAC scores were >4-fold higher for RA patients than for controls (18.6 versus 4.6 Agatston units, respectively; P < 0.001), a difference significantly greater than that in any other LDL concentration stratum except LDL concentration ≥160 mg/dl. Similarly, 32% of the RA patients with low LDL concentration had a CAC score of ≥100 Agatston units compared with only 7% of controls in the same LDL concentration stratum (odds ratio 5.97; P < 0.001), a difference significantly greater than that in all of the other LDL concentration strata. Low LDL concentration was most strongly associated with higher CAC score among RA patients who were white, had ever smoked, or were not obese. Other than a higher frequency of current smokers, RA patients with low LDL concentrations did not have more CVD risk factors or higher measures of RA disease activity or severity than RA patients with higher LDL concentrations. CONCLUSION: RA patients with low LDL concentration may represent a group for whom heightened screening and prevention of atherosclerotic CVD is appropriate.

Patterns of chromosomal variation in natural populations of the neoallotetraploid Tragopogon mirus (Asteraceae).

Cytological studies have shown many newly formed allopolyploids (neoallopolyploids) exhibit chromosomal variation as a result of meiotic irregularities, but few naturally occurring neoallopolyploids have been examined. Little is known about how long chromosomal variation may persist and how it might influence the establishment and evolution of allopolyploids in nature. In this study we assess chromosomal composition in a natural neoallotetraploid, Tragopogon mirus, and compare it with T. miscellus, which is an allotetraploid of similar age (~40 generations old). We also assess whether parental gene losses in T. mirus correlate with entire or partial chromosome losses. Of 37 T. mirus individuals that were karyotyped, 23 (62%) were chromosomally additive of the parents, whereas the remaining 14 individuals (38%) had aneuploid compositions. The proportion of additive versus aneuploid individuals differed from that found previously in T. miscellus, in which aneuploidy was more common (69%; Fisher's exact test, P=0.0033). Deviations from parental chromosome additivity within T. mirus individuals also did not reach the levels observed in T. miscellus, but similar compensated changes were observed. The loss of T. dubius-derived genes in two T. mirus individuals did not correlate with any chromosomal changes, indicating a role for smaller-scale genetic alterations. Overall, these data for T. mirus provide a second example of prolonged chromosomal instability in natural neoallopolyploid populations.

Tumor necrosis factor α inhibitor use and decreased risk for incident coronary events in rheumatoid arthritis.

OBJECTIVE: To determine the association of tumor necrosis factor α (TNFα) inhibitors with risk for cardiovascular disease (CVD) in rheumatoid arthritis (RA) patients. METHODS: A retrospective cohort of 2,101 incident RA patients was established. Medication exposure was categorized into the following groups: TNFα inhibitors alone or in combination with methotrexate (MTX; aTNF group); MTX alone or in combination with other nonbiologic disease-modifying antirheumatic drugs (DMARDs; MTX group); and no MTX, nonbiologic DMARDs (reference group). Primary outcome was adjudicated incident coronary artery disease (CAD), defined as myocardial infarction, unstable angina, or coronary revascularization procedure. Secondary outcome was adjudicated incident CVD, defined as a composite of CAD, stroke, transient ischemic attack, abdominal aortic aneurysm, peripheral arterial disease, or arterial revascularization procedure. Cox regression models were used to calculate the hazard ratio for CAD and CVD for the aTNF and MTX groups compared to the reference group. RESULTS: There were 46 incident CAD and 82 incident CVD events. Adjusting for covariates associated with CAD and CVD, the hazard ratio for incident CAD was 0.45 (95% confidence interval [95% CI] 0.21-0.96) for the aTNF group and 0.54 (95% CI 0.27-1.09) for the MTX group compared to the reference group. Use of TNFα inhibitors for >16.1 months was associated with a relative risk for CAD of 0.18 (95% CI 0.06-0.50) and for CVD of 0.31 (95% CI 0.15-0.65) compared to the reference group. A similar, although not significant, trend was seen with the MTX group. CONCLUSION: Use of TNFα inhibitors is associated with a decreased risk for CAD in RA; the risk decreases further with long-term use. This should be considered when weighing the risks versus benefits of these medications.

Diabetes mellitus risk in rheumatoid arthritis: reduced incidence with anti-tumor necrosis factor α therapy.

OBJECTIVE: To examine the association of tumor necrosis factor α (TNFα) inhibitor use and the risk of developing diabetes mellitus in a rheumatoid arthritis (RA) inception cohort. METHODS: Adults diagnosed with RA between January 1, 2001, and December 31, 2009, were identified (n = 1,881). Prevalent cases of diabetes mellitus (n = 294) were excluded. Information on sociodemographic data, medical history, body mass index (BMI), laboratory measures, and medications was collected from the electronic health record. Incident diabetes mellitus was defined using the 2010 American Diabetes Association criteria or physician-established diagnosis. Time-varying Cox proportional hazards regression models were used to adjust for age, sex, race, BMI, rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibodies (anti-CCP), erythrocyte sedimentation rate (ESR), and use of nonsteroidal antiinflammatory drugs (NSAIDs), glucocorticoids, hydroxychloroquine, and methotrexate. RESULTS: A total of 1,587 incident RA patients without diabetes mellitus were included. The anti-TNFα users (n = 522) had a lower median age but greater baseline BMI; maximum ESR, RF, and anti-CCP positivity; and NSAID, glucocorticoid, or methotrexate use. The median followup time for the ever and never TNFα inhibitor users was 44.9 months (interquartile range [IQR] 23.7-73.0 months) and 37.1 months (IQR 16.3-65.1 months), respectively (P < 0.001). Of the 91 patients developing diabetes mellitus, 16 were ever and 75 were never TNFα inhibitor users, yielding incidence rates of 8.6 and 17.2 per 1,000 person-years (P = 0.048), respectively. Adjusting for covariates, the hazard ratio for incident diabetes mellitus in TNFα inhibitor users was 0.49 (95% confidence interval 0.24-0.99, P = 0.049) compared to the never users. CONCLUSION: In this inception RA cohort, anti-TNFα use was associated with a 51% reduction in risk of developing diabetes mellitus.

Hydroxychloroquine use and decreased risk of diabetes in rheumatoid arthritis patients.

BACKGROUND/OBJECTIVES: Several studies have associated hydroxychloroquine use with decreased risk of diabetes mellitus (diabetes) or improved glycemic control in rheumatoid arthritis patients, but the studies were small or used data from self-report. The present study sought to replicate this protective relationship in a health system using electronic health records with laboratory data and physician diagnoses. METHODS: This study is a retrospective cohort of 1127 adults with newly diagnosed rheumatoid arthritis and no diabetes within the Geisinger Health System between January 1, 2003, and March 31, 2008. Patients were classified as ever users (n = 333) or never users (n = 794) of hydroxychloroquine. Incident diabetes cases were defined using 2010 American Diabetes Association criteria. RESULTS: The median follow-up times for the ever and never hydroxychloroquine users were 26.0 and 23.0 months, respectively (P = 0.28). The median duration of hydroxychloroquine exposure was 14.0 months. Of the 48 cases developing diabetes during observation, 3 were exposed to hydroxychloroquine at time of development and 45 were nonexposed, yielding incidence rates of 6.2 and 22.0 per 1000 per year (P = 0.03), respectively. In time-varying Cox proportional hazards regression models adjusting for sex, age, body mass index, positive rheumatoid factor and anti-cyclic citrullinated peptide antibodies, erythrocyte sedimentation rate, and nonsteroidal anti-inflammatory drug, glucocorticoid, methotrexate, and tumor necrosis factor α inhibitor use, the hazard ratio for incident diabetes among hydroxychloroquine users was 0.29 (95% confidence interval, 0.09-0.95; P = 0.04) compared with nonusers. CONCLUSIONS: Our findings support the potential benefit of hydroxychloroquine in attenuating the risk of diabetes in rheumatoid arthritis patients. Further work is needed to determine its potential preventive role in other groups at high risk for diabetes.

Patterns of preventive health services in rheumatoid arthritis patients compared to a primary care patient population.

To determine the proportion of rheumatoid arthritis (RA) patients receiving preventive health care according to US Preventive Services Task Force recommendations compared with a community-based population sample, with emphasis on dyslipidemia testing, given the increased risk of cardiovascular disease (CVD) in RA patients. Patients with RA (ICD-9 code 714.0 at ≥2 office visits with a rheumatologist) and a primary care physician (PCP) at the Geisinger Health System (GHS) were identified through electronic health records. The records were searched back from 3/31/08 for the length of time required to satisfy each outcome measure. Percentages were compared with population testing rates using the Pearson Chi-square test. Eight hundred and thirty-one RA patients were compared to 169,476 subjects with a PCP at GHS, stratified by gender and age. Patients with RA were more likely to have had dyslipidemia and osteoporosis testing compared with the general population (86 vs. 75 and 75 vs. 55%, respectively, P < 0.0001 for both). The proportion of RA patients receiving breast and cervical cancer testing was similar to the general population. The majority (79%) of lipid testing was ordered by PCPs. Those RA patients with recommended lipid testing had more traditional CVD factors (hypertension, diabetes, coronary artery disease). RA patients are screened more than the general population for two RA-related co-morbidities, i.e. dyslipidemia and osteoporosis. The RA patients with traditional cardiovascular risk factors are more likely to be tested for dyslipidemia. Further work is warranted to improve testing for modifiable CVD risk factors in this group with multiple co-morbidities.

Structural bone allograft in pediatric foot surgery.

Structural bone allografts are used in a variety of surgical procedures, but only a few investigators have examined their use and associated complications in the pediatric population specifically. In a retrospective review of pediatric foot procedures, we sought to determine types and rates of complications associated with structural bone allografts as well as time to incorporation of these allografts. Minimum follow-up was 12 months. Eighteen patients with 31 structural allografts were reviewed. The total complication rate was 7.1%, and the allograft incorporation rate was 90% (mean time after surgery, 9 months). Mean follow-up was 22 months. There were no pseudarthroses, nonunions, or fractures at the bone-graft sites. Structural bone allografts can be safely used in foot procedures in pediatric neuromuscular patients without major risk for complications, and their use can reduce autograft-harvest morbidity in pediatric patients with neuromuscular conditions.

A cancer research UK pharmacokinetic study of BPA-mannitol in patients with high grade glioma to optimise uptake parameters for clinical trials of BNCT.

This paper describes results to-date from a human pharmacokinetic study which began recruitment in December 2007. Results are presented for a single patient recruited in December 2007. A second patient was recruited in July 2008 but detailed data are not available at the time of writing. The trial is an open-label, non-comparative, non-therapeutic study of BPA-mannitol in patients with high-grade glioma, who will be undergoing stereotactic brain biopsy as part of the diagnostic process before definitive treatment. The study investigates the route of infusion (intra-venous (IV) or intra-carotid artery) and in each case will assess the effect of administration of mannitol as a blood-brain barrier disrupter. All cohorts will receive a 2 h infusion of BPA-mannitol, and for some cohorts an additional mannitol bolus will be administered at the beginning of this infusion. Measurements are made by inductively coupled plasma mass spectrometry (ICP-MS) of (10)B concentration in samples of blood, urine, extra-cellular fluid in normal brain (via a dialysis probe), brain tissue around tumour and tumour tissue. Additional analysis of the tumour tissue is performed using secondary ion mass spectrometry (SIMS). The first patient was part of the cohort having intra-venous infusion without mannitol bolus. No serious clinical problems were experienced and the assay results can be compared with available patient data from other BNCT centres. In particular we note that the peak (10)B concentration in blood was 28.1 mg/ml for a total BPA administration of 350 mg/kg which is very consistent with the previous experience with BPA-fructose reported by the Helsinki group.

Outcomes of gastrocnemius-soleus complex lengthening for isolated equinus contracture in children with cerebral palsy.

BACKGROUND: The goal of the gastrocnemius-soleus complex (GSC) lengthenings in children with cerebral palsy (CP) is to achieve a plantigrade foot and normalize kinematics during gait. The study purpose was to evaluate the results of GSC lengthening for isolated equinus contracture in individuals with CP. It was hypothesized that GSC lengthenings would normalize passive ankle range of motion, kinematic, kinetic, and temporal spatial parameters. METHODS: Gait data from 15 able-bodied participants from the laboratory normal database and passive range of motion, kinematic, kinetic, and temporal spatial gait parameters, and oxygen cost were collected and analyzed for 27 individuals with CP (36 limbs) with isolated equinus contracture who received GSC lengthenings. Data were compared between preoperative and postoperative assessments. RESULTS: Mean age at baseline was 11.4 years (+/-3.2 y). Mean time between surgery and postoperative gait analysis was 1.3 years (+/-0.3 y). Passive range of motion measurements were obtained. Kinematic and kinetic data for the hip, knee and ankle, and temporal spatial parameters were obtained from a representative gait trial preoperatively and postoperatively. Paired t tests (P<0.05) determined whether preoperative data differed from postoperative data or from able-bodied data. The passive range of motion at the ankle was improved and normalized postoperatively. Ankle kinematics normalized without compensatory changes occurring at the knee or hip kinematics. Ankle moments and powers become more normal but did not completely normalize. Kinematics and kinetics of the hip and knee were not adversely affected. No changes in the temporal spatial data or oxygen cost occurred postoperatively. CONCLUSIONS: These data support the finding that with appropriate patient selection isolated GSC lengthening does not result in overcorrection. LEVEL OF EVIDENCE: Retrospective comparative study; level 3.

C-reactive protein and coronary artery calcium in asymptomatic women with systemic lupus erythematosus or rheumatoid arthritis.

Patients with systemic lupus erythematosus (SLE) and those with rheumatoid arthritis (RA) have increased risk for atherosclerotic cardiovascular disease. The aims of this study were to compare the presence of coronary artery calcium (CAC) in age- and race-matched women with SLE, those with RA, and healthy controls without diabetes mellitus or history of myocardial infarction, angina pectoris, or stroke and to investigate its relation with traditional risk factors, inflammation, and endothelial activation. Study subjects completed cardiovascular risk factor assessment and electron-beam computed tomography that measured CAC. The 2 patient groups had similar prevalence and extent of CAC as well as significantly increased odds of having any CAC (odds ratio 1.87, 95% confidence interval 1.09 to 3.21) and more extensive CAC (odds ratio 4.04, 95% confidence interval 1.42 to 11.56 for CAC score >100) compared with healthy controls. After controlling for differences in cardiovascular risk factors, including insulin resistance and hypertension, the results remained statistically significant. After adjustment for differences in levels of C-reactive protein and/or soluble intercellular adhesion molecule-1, however, women with chronic inflammatory diseases no longer had significantly increased odds of having any CAC or more extensive CAC compared with controls. In conclusion, asymptomatic and nondiabetic women with chronic inflammatory diseases had significantly increased odds of having CAC and more extensive CAC compared with age- and race-matched healthy controls. The increased odds for CAC may in part result from higher levels of inflammation and endothelial activation in these patients.

ABO transcript levels in peripheral blood and erythropoietic culture show different allele-related patterns independent of the CBF/NF-Y enhancer motif and multiple novel allele-specific variations in the 5'- and 3'-noncoding regions.

BACKGROUND: Mechanisms regulating the ABO gene are unclear, especially in the hematopoietic compartment. The number of 43-bp repeats in the CBF/NF-Y-binding enhancer region is considered to have a major influence on transcription. STUDY DESIGN AND METHODS: Transcript levels in peripheral blood and in erythropoietic culture of CD34+ cells from marrow donors were measured with TaqMan assays. The 5'-regulatory region and 3'-downstream sequences were investigated to determine if allelic variations occur. RESULTS: Surprisingly, transcripts from A(1) and A(2) alleles could not be detected in peripheral blood, although transcripts from B/O(1)/O(1v)/O(2) alleles were readily observed. Sequencing of approximately 4 kb upstream and 1.8 kb downstream of the coding region showed multiple novel allele-specific and allele-related motifs. No correlation between these sequence variations and transcript levels was found, however. Contradictory to the results with peripheral blood, in erythropoietic culture of CD34+ cells from healthy marrow donors transcripts from A(1) and A(2) alleles were found at higher levels than transcripts from B/O(1)/O(1v) alleles. CONCLUSION: These data do not support previous suggestions that nonsense-mutated O(1)/O(1v) transcripts are eliminated first. Furthermore, our results contradict the notion that the number of repeats in the upstream CBF/NF-Y-binding enhancer region, which contains four 43-bp repeats in A(2)/B/O(1)/O(1v) but only one 43-bp unit in A(1)/O(2) alleles, determines the transcription rate. The reason for the remarkable discrepancy between blood and marrow remains to be elucidated.

Subclinical coronary artery calcification and relationship to disease duration in women with rheumatoid arthritis.

OBJECTIVE: To examine the association between disease duration of rheumatoid arthritis (RA) and the presence and extent of coronary artery calcification (CAC) in women with RA. METHODS: In this cross-sectional study, 185 women with RA duration of at least 2 years and no clinical cardiovascular disease completed electron-beam tomography (EBT) scans and risk factor assessment. Multivariable logistic regression was used to associate RA duration quartiles with subclinical CAC and extent of CAC. RESULTS: Age was similar across the quartiles of RA duration. Patients with RA > 23 years had significant increased odds (unadjusted OR 2.60, 95% CI 1.21 5.53) of having more extensive CAC compared to the referent group, those with RA for 2 7 years. This association remained significant after adjustment for traditional coronary heart disease (CHD) risk factors and RA-related covariates. Patients with intermediate RA duration (8 13 yrs) were more likely to have presence of any CAC (OR 3.03, 95% CI 1.06 8.66) compared to the referent group only after adjusting for age, race, and traditional CHD risk factors. Patients with longer RA duration were more likely to have cumulative joint damage, manifested as prior joint surgery, joint deformity, and greater functional disability. Lower body mass index also was associated with longer RA duration. CONCLUSION: Patients with longstanding RA have more extensive subclinical atherosclerosis or CAC compared to patients of the same age, independent of other CHD risk factors. RA duration may be a surrogate for factors related to the disease process or its treatment that may promote coronary atherogenesis.

Poor 1-year outcomes after percutaneous coronary interventions in systemic lupus erythematosus: report from the National Heart, Lung, and Blood Institute Dynamic Registry.

BACKGROUND: Women with systemic lupus erythematosus (SLE) have premature and accelerated atherosclerosis. Although percutaneous coronary intervention (PCI) is used frequently to treat coronary artery disease in SLE, little is known regarding PCI outcomes immediately after PCI and after discharge. METHODS AND RESULTS: Baseline demographic, procedure-related, and adverse outcome data on consecutive patients undergoing PCI during 5 recruitment "waves" of the National Heart, Lung, and Blood Institute Dynamic Registry across 23 clinical centers were collected. SLE patients (n=28) were compared with non-SLE patients (n=3385). SLE patients were younger and more often female in comparison with non-SLE patients undergoing PCI. SLE patients were less likely than non-SLE patients to have hyperlipidemia but had a similar prevalence of hypertension, diabetes mellitus, and tobacco use. The prevalence of multivessel disease was similar between groups. Initial intervention success (by angiographic definition) was not significantly different between groups. At 1 year, SLE patients were more likely to experience a myocardial infarction (15.6% versus 4.8%, P=0.01) and more often required repeat PCI (31.3% versus 11.8%, P=0.009) than non-SLE patients, even after adjustment for important covariates. CONCLUSIONS: SLE patients had significantly worse cardiovascular outcomes at 1 year than non-SLE patients. Even considering the small number of SLE patients, these differences were striking. Further study is warranted to explore other factors potentially accounting for this disparity, including SLE disease activity and duration, presence of hypercoagulable state, and immunosuppressive therapy.

Coronary artery bypass graft imaging using ECG-gated multislice computed tomography: comparison with catheter angiography.

AIM: To compare the value of multislice computerized tomography (MSCT) in imaging coronary artery bypass grafts (CABGs) by direct quantitative comparison with standard invasive angiography. METHODS: Using MSCT, 50 consecutive patients who had previously undergone CABG surgery and had recently undergone invasive angiography for recurrent angina pectoris, were studied further using MSCT after intravenous injection of non-ionic contrast agent; cardiac imaging was performed during a single breath-hold. Graft anatomy was quantified, using both quantitative coronary angiography (QCA) and MSCT, by different investigators blinded to each other. Reproducibility was quantified using the standard error of the measurement expressed as a percentage in log-transformed values (CV%) and intraclass correlation (ICC). RESULTS: All 150 grafts were imaged using MSCT; only 4 patent grafts were not imaged using selective angiography. Good agreement was achieved between MSCT and QCA on assessment of proximal anastomoses (CV% 25.2, ICC 0.84), mid-vessel luminal diameter (CV% 15.5, ICC 0.91) and aneurysmal dilations (CV% 14.3). Reasonable agreement was reached on assessment of distal anastomoses (CV% 26.7, ICC 0.66) and categorization of distal run-off (ICC 0.73). Good agreement was observed for stenoses of over 50% luminal loss (CV% 8.7, ICC 0.97) but agreement on assessment of less severe lesions was poor (CV% 208.7, ICC 0.51). CONCLUSION: This study demonstrates that CABGs can be quantitatively evaluated using MSCT, and that significant lesions present in all CABG segments can be reliably identified. Agreement between MSCT and QCA for lesions of less than 50% luminal loss was poor.

Health related quality of life of patients with refractory angina before and one year after enrolment onto a refractory angina program.

OBJECTIVE: This study was designed to assess the impact of a refractory angina programme on the health related quality of life for patients with chronic refractory angina (CRA) one year following enrolment. DESIGN: A one year prospective audit. SETTING: Specialist refractory angina clinic at a tertiary cardiac referral centre. PATIENTS: 69 consecutive refractory angina patients referred to a regional refractory angina centre from 1/03/2001 to 1/09/2002. INTERVENTIONS: Pain treatment algorithm in accordance with the recommendations of the national refractory angina guideline committee. MAIN OUTCOME MEASURES: Improvements in quality of life indices were assessed using Seattle angina questionnaire (SAQ), and short form-12 (SF-12) with changes in mood determined using the hospital anxiety and depression (HAD) questionnaire. RESULTS: All dimensions of the SF-12 and SAQ were superior at one year with significant improvement seen with the mental component of SF-12 (p = 0.023), and four of the five SAQ domains, angina stability (p = 0.028), angina frequency (p=0.02), treatment satisfaction (p=0.001) and quality of life (p < 0.001). All the significant changes within the SAQ domains were large enough to be considered clinically relevant. At one year the anxiety and depression domains were significantly improved from baseline (p = 0.015, 0.018) with clinical anxiety levels falling significantly from 55% to 40%, a relative reduction of 28% (p = 0.008). CONCLUSIONS: Implementation of the national refractory angina guidelines in a prospective study of 69 consecutive CRA patients significantly improved health related quality of life status at one year.

Comorbid conditions in patients with rheumatic diseases: an update.

PURPOSE OF REVIEW: This review summarizes recent literature (September 2002 to September 2003) on three comorbid conditions (infection, cardiovascular disease, and malignancy) in patients with rheumatic disease. RECENT FINDINGS: Infection risk in rheumatoid arthritis is increased as a result of treatment and the disease itself. Atherosclerotic cardiovascular events are increased in rheumatoid arthritis. Although cardiovascular events also are increased in lupus, screening for cardiovascular risk factors in these patients is suboptimal. The incidence of malignancy overall and specifically the incidence of lymphoma are not increased in patients with rheumatoid arthritis on antitumor necrosis factor therapy compared with patients with rheumatoid arthritis in general. SUMMARY: Rheumatologists must be aware of the risk of infection, atherosclerotic events, and cancers in their patients. As prognosis for rheumatic disease patients continues to improve, the impact of comorbid conditions on morbidity and mortality is more apparent. Further research is needed to elucidate the relative contributions of the underlying autoimmune diseases and their treatments on these conditions that affect long-term patient survival.

The simultaneous use of a biventricular implantable cardioverter defibrillator (ICD) and transcutaneous electrical nerve stimulation (TENS) unit: implications for device interaction.

Undesirable sensing of external sources of electromagnetic interference by ICDs is well known. A transcutaneous electrical nerve stimulation (TENS) device has been reported to interfere with an ICD resulting in an inappropriate shock and patients with implanted defibrillators or pacemakers have been cautioned about the use of such units to treat chronic pain. We describe a patient regularly using TENS therapy for pain who subsequently received a biventricular ICD for malignant ventricular arrhythmias and medically refractory cardiac failure. He underwent testing for device interaction immediately post-implant. This did not show inappropriate sensing by either ICD or pacemaker component of his heart failure device. However, six months later, the patient complained of dizziness and bradycardia with application of TENS. Further testing did reveal interference with pacemaker function. Thus, even if initial testing is negative and reassuring, patients with a biventricular ICD still require careful follow-up for potential interaction and should be cautioned against the use of TENS, especially if they are pacemaker-dependent.

Genomic analysis of clinical samples with serologic ABO blood grouping discrepancies: identification of 15 novel A and B subgroup alleles.

Since the cloning in 1990 of complementary DNA corresponding to messenger RNA transcribed at the blood group ABO locus, polymorphisms and phenotype-genotype correlations have been reported by several investigators. Exons 6 and 7, constituting 77% of the gene, have been analyzed previously in samples with variant phenotypes but for many subgroups the molecular basis remains unknown. This study analyzed 324 blood samples involved in ABO grouping discrepancies and determined their ABO genotype. Samples from individuals found to have known subgroup alleles (n = 53), acquired ABO phenotypes associated with different medical conditions (n = 65), probable chimerism (n = 3), and common red blood cell phenotypes (n = 109) were evaluated by ABO genotype screening only. Other samples (n = 94) from apparently healthy donors with weak expression of A or B antigens were considered potential subgroup samples without known molecular background. The full coding region (exons 1-7) and 2 proposed regulatory regions of the ABO gene were sequenced in selected A (n = 22) or B (n = 12) subgroup samples. Fifteen novel ABO subgroup alleles were identified, 2 of which are the first examples of mutations outside exon 7 associated with weak subgroups. Each allele was characterized by a missense or nonsense mutation for which screening by allele-specific primer polymerase chain reaction was performed. The novel mutations were encountered in 28 of the remaining 60 A and B subgroup samples but not among normal donors. As a result of this study, the number of definable alleles associated with weak ABO subgroups has increased from the 14 previously published to 29.

'Cold hand, ischemic heart': treatment by stenting of the left subclavian artery.

A 59-year-old man presented with worsening angina and a cold, painful left hand, eight years after coronary artery bypass surgery. Coronary angiography showed extensive coronary atherosclerosis with blocked vein grafts to his left circumflex and right coronary arteries. There was a severe narrowing in the left subclavian artery before the origin of the left internal mammary artery (LIMA) which appeared patent. PTCA and stent implantation to the left subclavian artery stenosis restored normal flow to the left hand and the LIMA with abolition of his ischemic hand symptoms and marked improvement of his angina.