Subspecialisation in cardiology care and outcome: should clinical services be redesigned, again?

BACKGROUND: Inpatient management of cardiac patients by cardiologists results in reduced mortality and hospitalisation. With increasing subspecialisation of the field because of growing management complexity and use of technological innovations, the impact of sub-specialisation on patient outcomes is unclear. AIM: To investigate whether management by subspecialty cardiologists impacts the outcomes of patients with subspecialty-specific diseases. METHODS: All patients admitted to a tertiary centre over nine years with a diagnosis of heart failure, acute coronary syndrome (ACS) or primary arrhythmia were reviewed. The outcomes of these patients managed by cardiologists subspecialised in their admission diagnosis (heart failure specialists, interventionalists and electrophysiologists) were compared with those treated by general cardiologists. RESULTS: Heart failure was diagnosed in 1704 patients, ACS in 7763 and arrhythmia in 4398. There was no difference in length of stay (LOS) (P = 0.26), mortality (P = 0.57) or cardiovascular readmissions (P = 0.50) in heart failure patients treated by general cardiologists compared with subspecialists. In ACS patients, subspecialty management was associated with reduced LOS, cardiovascular readmissions and mortality (all P < 0.05). This reduction in mortality was seen mainly in lower risk patients (P < 0.05). There was a reduction in LOS and cardiovascular readmissions in arrhythmia patients receiving subspecialty management (both P < 0.05) but no difference in mortality (P = 0.14). ACS patients managed by interventionalists were more likely to undergo coronary intervention (P < 0.05). Electrophysiologists more frequently referred patients for catheter ablation and pacemaker implantation than general cardiologists (P < 0.05). CONCLUSIONS: The benefits of subspecialty care seem attributable to the appropriate selection of patients who would benefit from technological innovations in care. These results suggest that the development of healthcare systems which align cardiovascular disease with the subspecialist may be more effective.

Effects of simulated domestic and international air travel on sleep, performance, and recovery for team sports.

The present study examined effects of simulated air travel on physical performance. In a randomized crossover design, 10 physically active males completed a simulated 5-h domestic flight (DOM), 24-h simulated international travel (INT), and a control trial (CON). The mild hypoxia, seating arrangements, and activity levels typically encountered during air travel were simulated in a normobaric, hypoxic altitude room. Physical performance was assessed in the afternoon of the day before (D - 1 PM) and in the morning (D + 1 AM) and afternoon (D + 1 PM) of the day following each trial. Mood states and physiological and perceptual responses to exercise were also examined at these time points, while sleep quantity and quality were monitored throughout each condition. Sleep quantity and quality were significantly reduced during INT compared with CON and DOM (P < 0.01). Yo-Yo Intermittent Recovery level 1 test performance was significantly reduced at D + 1 PM following INT compared with CON and DOM (P < 0.01), where performance remained unchanged (P > 0.05). Compared with baseline, physiological and perceptual responses to exercise, and mood states were exacerbated following the INT trial (P < 0.05). Attenuated intermittent-sprint performance following simulated international air travel may be due to sleep disruption during travel and the subsequent exacerbated physiological and perceptual markers of fatigue.

A Year of Fractures: a snapshot analysis of the logistics, problems and outcomes of a hospital-based fracture liaison service.

SUMMARY: Our fracture liaison service identifies patients with low trauma fractures, determines the need for osteoporosis therapy and instigates therapy if necessary. We describe the tracking and outcome of 768 patients attending our emergency department over 1 year and discuss the problems we encountered and potential solutions. INTRODUCTION: Osteoporotic fractures result in substantial morbidity, mortality and economic cost, and patients sustaining a first fracture are known to be at higher risk of sustaining future fracture. Treatment of at-risk patients has been shown to assist in prevention of future fracture including hip fracture. We established a "First Fracture Project" to identify and treat these patients in 2003. METHODS: We assessed "A Year of Fractures": the logistics, outcome and problems in tracking patients presenting to our emergency department with a low trauma fracture by our fracture liaison service, over 1 year from July 2008 to June 2009. Patients were tracked by our osteoporosis nurse and offered assessment, and treatment where necessary. RESULTS: In 1 year, 768 patients aged 50 or over were identified from emergency department records as attending with a low trauma fracture. About 84 % of patients eventually received assessment. Of the162 patients progressing through the entire process, 74 % had osteoporosis treatment planned and/or commenced. CONCLUSIONS: Our fracture liaison service was effective at identifying most low trauma fracture patients at risk of further fracture and providing access to osteoporosis assessment. There were many difficulties: we outline logistic and practical issues in delivering our service and suggest potential improvements.

Patterns of inflammatory activation associated with precipitants of acute coronary syndromes: a case-crossover study.

AIMS: We sought to assess a broad array of possible precipitants of acute coronary syndromes (ACS) and evaluate their association with detectable inflammatory activation. METHODS AND RESULTS: Within a case-crossover design, using a standardised questionnaire, interviews among 348 ST-elevation myocardial infarction (44%) or high-risk non-ST-elevation ACS patients (56%), explored potential precipitants, including: infection (INF)-temperature >38°C and/or respiratory tract, urinary or skin infection; inflammation (INFL)-exacerbation of inflammatory conditions; exercise (EX)-moderate to heavy exercise; fast food (FF)-consumption of a meal purchased from a fast food company. Risk and control periods were: weekly over 8 weeks for INF and INFL; 24 hourly over 4 days for FF and 4 hourly over 48 h for EX. C-reactive protein (CRP) levels were assessed at admission. These precipitants were identified in 203/348 (58.3%) patients. An increased temporal risk was observed for: INF (0-7 days vs 7-8 weeks odds ratio (OR): 7.5, confidence interval (CI): 1.7-67.6, P = 0.002); INFL (0-7 days vs 7-8 weeks OR: 14.0, CI: 2.13-591.9, P = 0.001); EX (0-4 h vs 24-28 h OR: 2.2, CI: 1.3-3.5, P = 0.001) and FF (0-24 h vs 72-96 h OR: 5.67, CI: 1.6-30.2, P = 0.003). CRP levels were significantly elevated among patients reporting infective and inflammatory potential precipitants, but not among those reporting fast food consumption and unaccustomed moderate-heavy exercise. CONCLUSION: Infection, inflammatory conditions, moderate-heavy exercise and potentially fast food consumption appear to precipitate high-risk ACS. Increased inflammation as measured by CRP was not consistently detected despite the identification of an ACS precipitant. Strategies that target improved overall health may also lead to fewer ACS events through a reduction in triggers.

Effect of cold water immersion on repeated cycling performance and limb blood flow.

The purpose of the present study was to compare the effects of cold water immersion (CWI) and active recovery (ACT) on resting limb blood flow, rectal temperature and repeated cycling performance in the heat. Ten subjects completed two testing sessions separated by 1 week; each trial consisted of an initial all-out 35-min exercise bout, one of two 15-min recovery interventions (randomised: CWI or ACT), followed by a 40-min passive recovery period before repeating the 35-min exercise bout. Performance was measured as the change in total work completed during the exercise bouts. Resting limb blood flow, heart rate, rectal temperature and blood lactate were recorded throughout the testing sessions. There was a significant decline in performance after ACT (mean (SD) -1.81% (1.05%)) compared with CWI where performance remained unchanged (0.10% (0.71%)). Rectal temperature was reduced after CWI (36.8°C (1.0°C)) compared with ACT (38.3°C (0.4°C)), as was blood flow to the arms (CWI 3.64 (1.47) ml/100 ml/min; ACT 16.85 (3.57) ml/100 ml/min) and legs (CW 4.83 (2.49) ml/100 ml/min; ACT 4.83 (2.49) ml/100 ml/min). Leg blood flow at the end of the second exercise bout was not different between the active (15.25 (4.33) ml/100 ml/min) and cold trials (14.99 (4.96) ml/100 ml/min), whereas rectal temperature (CWI 38.1°C (0.3°C); ACT 38.8°C (0.2°C)) and arm blood flow (CWI 20.55 (3.78) ml/100 ml/min; ACT 23.83 (5.32) ml/100 ml/min) remained depressed until the end of the cold trial. These findings indicate that CWI is an effective intervention for maintaining repeat cycling performance in the heat and this performance benefit is associated with alterations in core temperature and limb blood flow.

Intravenous zoledronic acid and oral alendronate in patients with a low trauma fracture: experience from an osteoporosis clinic.

BACKGROUND/AIMS: Oral bisphosphonates have been shown to be effective in treating osteoporosis. However, there has been a significant problem with compliance. Newer intravenous bisphosphonates are available for osteoporosis management, but have not been compared with oral bisphosphonates in a clinical setting. The aim of this study was to compare the safety and effectiveness of intravenous zoledronic acid (ZOL) and oral alendronate (ALN) in osteoporotic patients following a low trauma fracture. METHODS: A non-randomized, retrospective cohort study was conducted of 169 patients with a low trauma fracture and reduced bone mineral density (BMD). Patients were treated with either an infusion of 4 mg ZOL or ALN 70 mg weekly. The outcomes measured were change in BMD after 12 months of treatment with either bisphosphonate, and new osteoporotic fractures. All adverse events were documented. RESULTS: Lumbar spine BMD (L2-L4) improved 5.6% in the ZOL group (P < 0.001) and 5.5% in the ALN group (P < 0.001). Total hip BMD improved 2% in the ZOL group (P < 0.01) and 2.5% in the ALN group (P < 0.001). There was no significant difference in BMD change between the groups. There were significantly more new fractures (P < 0.001) in the ZOL group (7.2%) than the ALN group (1%). The ZOL group were significantly older (P < 0.01) and had a significantly higher proportion of males (P < 0.05) at baseline. There were no serious adverse reactions in either group. CONCLUSION: ZOL and ALN both produce a significant increase in BMD and are well tolerated in patients with osteoporotic, low trauma fractures. Yearly ZOL provides a safe, convenient alternative to weekly oral bisphosphonates.

Effect of hydrotherapy on recovery from fatigue.

The present study investigated the effects of three hydrotherapy interventions on next day performance recovery following strenuous training. Twelve cyclists completed four experimental trials differing only in 14-min recovery intervention: cold water immersion (CWI), hot water immersion (HWI), contrast water therapy (CWT), or passive recovery (PAS). Each trial comprised five consecutive exercise days of 105-min duration, including 66 maximal effort sprints. Additionally, subjects performed a total of 9-min sustained effort (time trial - TT). After completing each exercise session, athletes performed one of four recovery interventions (randomly assigned to each trial). Performance (average power), core temperature, heart rate (HR), and rating of perceived exertion (RPE) were recorded throughout each session. Sprint (0.1 - 2.2 %) and TT (0.0 - 1.7 %) performance were enhanced across the five-day trial following CWI and CWT, when compared to HWI and PAS. Additionally, differences in rectal temperature were observed between interventions immediately and 15-min post-recovery; however, no significant differences were observed in HR or RPE regardless of day of trial/intervention. Overall, CWI and CWT appear to improve recovery from high-intensity cycling when compared to HWI and PAS, with athletes better able to maintain performance across a five-day period.

First Fracture Project: addressing the osteoporosis care gap.

Patients sustaining a low-trauma fracture are at greater risk of subsequent fracture, but as a group are poorly managed. We report the development of our 'First Fracture Project', in which we attempt to assess all patients over 50 years of age with a low-trauma fracture attending orthopaedic fracture clinics and treat osteopenia and osteoporosis. We found that the First Fracture Project has greatly increased our success in improving delivery of osteoporosis care to appropriate at-risk patients.

Effect of leflunomide on the peripheral nerves in rheumatoid arthritis.

BACKGROUND: The objective of this study was to determine the neurophysiological effects of leflunomide on peripheral nerves in rheumatoid arthritis. METHODS: We conducted a prospective cohort trial of 32 patients with rheumatoid arthritis with 16 patients receiving leflunomide treatment and 16 receiving other disease-modifying anti-rheumatic drug therapies. Clinical, laboratory and neurophysiological measurements were used to determine the presence of a peripheral neuropathy in these patients at study entry and then after a further 3 and 6 months. RESULTS: Fifty-four per cent of the leflunomide group and 8% of the control group had an increase in their neuropathy symptom score 6 months into the study (P = 0.01). No correlation was found between the electrophysiological findings and the clinical symptoms. There was no significant difference between the two groups in upper and lower limb sensory and motor amplitudes and conduction velocities recorded at 3 and 6 months. One patient developed both clinical and neurophysiological evidence of a peripheral neuropathy 5 months into the study that improved after cessation of leflunomide therapy and cholestyramine washout. CONCLUSION: After 6 months of exposure we found that leflunomide was associated with an apparent increase in the clinical symptoms of peripheral neuropathy in patients with rheumatoid arthritis. These symptoms did not correlate with neurophysiological studies.

Morbidity, mortality and economic burden of renal impairment in cardiac intensive care.

BACKGROUND: Moderate to severe impairment of renal function has emerged as a potent risk factor for adverse short- and long-term outcomes among patients presenting with cardiac disease. AIMS: We sought to define the clinical, late mortality and economic burden of this risk factor among patients presenting to cardiac intensive care. METHODS: A clinical audit of patients presenting to cardiac intensive care was undertaken between July 2002 and June 2003. All patients presenting with cardiac diagnoses were included in the study. Baseline creatinine levels were assessed in all patients. Late mortality was assessed by the interrogation of the National Death Register. Renal impairment was defined as estimated glomerular filtration rate <60 mL/min per 1.73 m2, as calculated by the Modified Diet in Renal Disease formula. In-hospital and late outcomes were compared by Cox proportional hazards modelling, adjusting for known confounders. A matched analysis and attributable risk calculation were undertaken to assess the proportion of late mortality accounted for by impairment of renal function and other known negative prognostic factors. The in-hospital total cost associated with renal impairment was assessed by linear regression. RESULTS: Glomerular filtration rate <60 mL/min per 1.73 m2 was evident in 33.0% of this population. Among these patients, in-hospital and late mortality were substantially increased: risk ratio 13.2; 95% CI 3.0-58.1; P < 0.001 and hazard ratio 6.2; 95% CI 3.6-10.7; P < 0.001, respectively. In matched analysis, renal impairment to this level was associated with 42.1% of all the late deaths observed. Paradoxically, patients with renal impairment were more conservatively managed, but their hospitalizations were associated with an excess adjusted in-hospital cost of $A1676. CONCLUSION: Impaired renal function is associated with a striking clinical and economic burden among patients presenting to cardiac intensive care. As a marker for future risk, renal function accounts for a substantial proportion of the burden of late mortality. The burden of risk suggests a greater potential opportunity for improvement of outcomes through optimisation of therapeutic strategies.

Telopeptides as markers of bone turnover in rheumatoid arthritis and osteoarthritis.

AIMS: The aim of the present study was to determine if urinary excretion of type I collagen N-terminal telopeptides (UrNTx) and deoxypyridinoline (UrDPD) and serum levels of type I collagen C-terminal telopeptides (SeCTx) differed in patients with rheumatoid arthritis (RA) compared with populations matched for age and gender with and without osteoarthritis (OA). The correlation of markers of bone turnover with disease activity in patients with RA or radiographic severity in patients with OA was also examined. METHODS: Patients with RA aged >50 years (men) and >60 years (women) were identified from computer databases at two tertiary referral centres for rheumatology. Strict exclusion criteria were applied to avoid the effects of factors known to influence markers of bone turnover. Patients with RA and OA were matched for age and sex with a control population free of known arthritic disease and a population with OA. Bone markers were assayed in serum and urine. Urine markers were measured on three consecutive days and mean values used to minimize day-to-day variability of these analytes. RESULTS: The level of UrNTx was elevated in patients with RA compared with normal controls and patients with OA. UrNTx and UrDPD correlated with markers of disease activity in patients with RA (erythrocyte -sedimentation rate and C-reactive protein), but not with -clinical signs of inflammation (swollen and tender joint counts). Patients with OA failed to show any correlation between markers of bone turnover and radiographic severity. CONCLUSIONS: These data support a role for the use of UrNTx and UrDPD in further studies of the patho-physiology of RA and in longitudinal studies designed to modify the course of clinical disease.

Alcohol consumption alters insulin secretion and cardiac autonomic activity.

BACKGROUND: Alcohol may have a cardioprotective effect. One possible mechanism is by modifying insulin resistance/secretion. The aims of this study were: (i) to examine the effect of short-term alcohol consumption on the metabolic control of glucose tolerance; (ii) to study the influence of short-term alcohol consumption on cardiac autonomic activity using spectral analysis of heart rate variability. METHODS: Twenty-one healthy subjects, in a randomized crossover design, either received three units of ethanol daily for 1 week or abstained from ethanol. The control of glucose tolerance was assessed using the intravenous glucose tolerance test with minimal modelling. RESULTS: There was no difference in fasting glucose, fasting insulin or insulin sensitivity between the two groups. Alcohol showed a lower insulin first phase insulin response (no alcohol 659.0 +/- 394.1 SD, alcohol 535.2 +/- 309.1) pmol L-1 min-1, P = 0.027). There was no difference in heart rate or blood pressure but a significant difference in the ratio of high to low frequency spectral power of heart rate variability; (no alcohol 4.55 +/- 3.78, alcohol 8.16 +/- 6.77, P = 0.033). This suggests decreased sympathetic and/or increased vagal modulation of heart rate in the alcohol group. CONCLUSION: The finding of no difference in insulin sensitivity between the two groups contrasts with, but does not entirely contradict, the results of previous epidemiological studies--perhaps suggesting that longer term changes such as liver enzyme induction may be important. The difference in insulin secretion questions the validity of previous studies of the influence of alcohol on insulin sensitivity, where insulin levels were used as a surrogate for insulin resistance.

Effects of angiotensin II (AT1) receptor blockade on cardiac vagal control in heart failure.

The objective of the present study was to determine the autonomic effects of angiotensin II (AT(1)) receptor blocker therapy in heart failure. In a randomized double-blind cross-over study, we compared the effects of candesartan and placebo on baroreflex sensitivity and on heart rate variability at rest, during stress and during 24 h monitoring. Acute effects were assessed 4 h after oral candesartan (8 mg) and chronic effects after 4 weeks of treatment (dose titrated to 16 mg daily). The study group comprised 21 patients with heart failure [mean (S.E.M.) ejection fraction 33% (1%)], in the absence of angiotensin-converting enzyme (ACE) inhibitor therapy. We found that acute candesartan was not different from placebo in its effects on blood pressure or mean RR interval. Chronic candesartan significantly reduced blood pressure [placebo, 137 (3)/82 (3) mmHg; candesartan, 121 (4)/75 (2) mmHg; P<0.001; values are mean (S.E.M.)], but had no effect on mean RR interval [placebo, 857 (25) ms; candesartan, 857 (21) ms]. Compared with placebo there were no significant effects of acute or chronic candesartan on heart rate variability in the time domain and no consistent effects in the frequency domain. Baroreflex sensitivity assessed by the phenylephrine bolus method was significantly increased after chronic candesartan [placebo, 3.5 (0.5) ms/mmHg; candesartan, 4.8 (0.7) ms/mmHg; P<0.05], although there were no changes in cross-spectral baroreflex sensitivity. Thus, in contrast with previous results with ACE inhibitors, angiotensin II receptor blockade in heart failure did not increase heart rate variability, and there was no consistent effect on baroreflex sensitivity.

Is high titre ANA specific for connective tissue disease?

OBJECTIVE: A positive antinuclear antibody (ANA), while sensitive, is not specific for systemic lupus erythematosus or connective tissue diseases (CTD). The purpose of the present study was to review those sera with a high titre (> or = dilutions above screening) ANA and determine from a review of the charts if these higher titres offered a satisfactory specificity for CTD. METHODS: All FANA testing in this region is carried out in one of two related laboratories. We reviewed the medical records of patients who had a positive ANA at a titre 4 dilutions above screening at this city-wide laboratory over a 6-month period to determine whether this titre ("high titre") may offer relative diagnostic certainty. Antibodies to extractable nuclear antigens (ENA) and native DNA were also obtained. RESULTS: 422 ANA results were positive at high titre. The medical record was available for review in 320 patients, of whom 238 (75%) were seen by a specialist physician, almost always including a rheumatologist. Our review determined that 35% had a diagnosis of connective tissue disease, 21% had a diagnosis of a possible/probable inflammatory disease, 16% had an alternative specific diagnosis provided, and in 29% no final disease specific diagnosis was recorded but CTD was not suggested to us or the specialist by the data available. One or more anti-ENA antibodies and/or anti-DNA were positive in 69 (22%) and 8% of the sera tested respectively. CONCLUSION: While long term follow-up is still required, a significant proportion of patients with high titre ANA have no CTD at the time of testing. Setting a higher cutoff for reporting of ANA may not increase specificity sufficiently to make it a useful alternative or addition to reporting a positive or negative value at screening titre alone.

Nitric oxide and cardiac autonomic control in humans.

Cardiac autonomic control is of prognostic significance in cardiac disease, yet the control mechanisms of this system remain poorly defined. Animal data suggest that nitric oxide (NO) modulates cardiac autonomic control. We investigated the influence of NO on the baroreflex control of heart rate in healthy human subjects. In 26 healthy male volunteers (mean age, 23+/-5 years), we measured heart rate variability and baroreflex sensitivity during inhibition of endogenous NO production with N(G)-monomethyl-L-arginine (L-NMMA) (3 mg/kg per hour) and during exogenous NO donation with sodium nitroprusside (1 to 3 mg/h). Increases from baseline (Delta) in high-frequency (HF) indexes of heart rate variability were smaller with L-NMMA in comparison to an equipressor dose of the control vasoconstrictor phenylephrine (12 to 42 microg/kg per hour): Deltaroot mean square of successive RR interval differences (DeltaRMSSD)=23+/-32 versus 51+/-48 ms (P<0.002); Deltapercentage of successive RR interval differences >50 ms (DeltapNN50)=5+/-15% versus 14+/-12% (P<0.05); and DeltaHF normalized power=-2+/-7 versus 9+/-8 normalized units (P<0.01), respectively. Relative preservation of these indexes was observed during unloading of the baroreflex with sodium nitroprusside compared with a matched fall in blood pressure produced by a control vasodilator, hydralazine (9 to 18 mg/h): DeltaRMSSD=-8+/-8 versus -24+/-15 ms (P<0.001); DeltapNN50=-6+/-11% versus -15+/-19% (P<0.01); DeltaHF normalized power=-7+/-13 versus -13+/-11 normalized units (P<0.05), respectively. The change in cross-spectral alpha-index calculated as the square root of the ratio of RR interval power to systolic spectral power in the HF band (although not alpha-index calculated in the same way for the low-frequency bands or baroreflex sensitivity assessed by the phenylephrine bolus method) was attenuated with L-NMMA compared with phenylephrine (Delta=4+/-8 versus 14+/-15 ms/mm Hg, respectively; P<0.02) and with sodium nitroprusside compared with hydralazine (Delta=-7+/-6 and -9+/-7 ms/mm Hg, respectively; P<0.05). In conclusion, these data demonstrate that NO augments cardiac vagal control in humans.

The effects of acute and chronic dihydropyridine calcium antagonist therapy on baroreflex sensitivity: a re-analysis using the sequence method.

The objective of this study was to examine the effects of dihydropyridine calcium antagonist therapy on 24-h baroreflex sensitivity. Twenty-three patients with moderate essential hypertension were studied before and during acute (10 patients) and chronic (21 patients) treatment with a dihydropyridine calcium antagonist (nifedipine, nicardipine or felodipine) as monotherapy in a dose titrated to produce a fall in mean cuff pressure of at least 10%. Twenty-four hour unrestricted ambulatory intra-arterial blood pressure (IABP) and heart rate (R-R interval) were monitored. Baroreflex sensitivity (BRS) was assessed throughout the 24-h period by off-line computer analysis of spontaneous variations in IABP and R-R interval. During acute first dose treatment with a calcium antagonist there was a significant fall in blood pressure (BP), increase in heart rate and reduction in BRS. With chronic therapy (6-16 weeks) there was a continued reduction in mean BP of 11% (P < 0.001), but heart rate had returned to control levels and BRS was significantly increased over the 24 h by 14% (P < 0.01). The increase in BRS was evident during both the waking and sleeping periods, but the greatest increase was during sleep (awake 12% P = 0. 02, asleep 28% P = 0.003). In conclusion, although dihydropyridine calcium antagonists acutely cause a reflex tachycardia associated with a reduced BRS, there is no such effect with chronic therapy. BRS was significantly increased after chronic treatment, with exaggeration of the diurnal pattern. Journal of Human Hypertension (2000) 14, 189-194.

LMP2 polymorphism is associated with extraspinal disease in HLA-B27 negative Caucasian and Mexican Mestizo patients with ankylosing spondylitis.

OBJECTIVE: To determine the effects of HLA Class II genes, particularly LMP2 and previously implicated Class I genes, on susceptibility and disease expression in HLA-B27 negative ankylosing spondylitis (AS). METHODS: Patients included 41 HLA-B27 negative Caucasians from a total AS population of 546 and 17 HLA-B27 negative Mexican Mestizo. Controls included 4352 random HLA-B27 negative Caucasians. LMP2 genotype assignments were made on all patients and 282 random Caucasian controls by polymerase chain reaction-restriction fragment length polymorphism with the Cfo I restriction enzyme while HLA typing was performed on patients and controls using microcytotoxicity assays for Class I, and sequence specific probe-PCR for HLA-B60, B39, B38, and DR. RESULTS: The LMP2BB genotype was significantly decreased in Caucasian AS patients without extraspinal (ES) disease (25%) compared to AS patients with ES (64.7%) (p = 0.01) and random Caucasian controls (53.9%) (p = 0.007), even when those with colitis and psoriasis were excluded from analysis (ES+ 55.6% versus ES- 22.2%). This finding remained significant after stratification by HLA-DR. Similar trends were noted in the Mexican population. A potential role for HLA-DR8 and DR2 in susceptibility to disease was observed in Caucasian patients, although this observation requires confirmation. We could not confirm reported associations with HLA-B60 or B39. Peripheral arthritis was significantly more commonly observed in those who had had acute anterior uveitis (AAU) (75%) than in those who had not developed AAU (27.3%) (p = 0.04). CONCLUSION: HLA Class II encoded genes may have effects on disease susceptibility and/or phenotype in HLA-B27 negative individuals similar to those noted in HLA-B27 positive AS. Eccentric and axial phenotypes of disease may be immunogenetically determined.

Use of opposing reflex stimuli and heart rate variability to examine the effects of lipophilic and hydrophilic beta-blockers on human cardiac vagal control.

Evidence from animal studies suggests that beta-blockers can act within the central nervous system to increase cardiac vagal motoneuron activity. We have attempted to determine whether such an effect is evident in healthy humans, by examining the effects of lipophilic and hydrophilic agents on heart rate variability and cardiac vagal reflexes. A total of 20 healthy volunteers took part in the study. Autonomic studies were performed after 72 h of treatment with placebo, atenolol or metoprolol in a blinded cross-over design. ECG recordings were taken at rest and during mental and orthostatic stress. Heart rate variability was measured in the time and frequency domains. The effects on heart rate of two opposing cardiac vagal reflexes were examined. Trigeminal stimulation causing vagal stimulation, and isometric forearm muscle contraction ('muscle heart reflex') causing vagal inhibition, were performed alone and simultaneously. At rest, during mental stress and during trigeminal stimulation, beta-blocker therapy was associated with significantly increased high-frequency beat-to-beat heart rate variability when compared with placebo. There were no significant differences in effects on heart rate or heart rate variability between atenolol and metoprolol. Analysis of the muscle heart reflex, alone and with simultaneous trigeminal stimulation, showed that the magnitude of the R-R interval response was significantly greater after beta-blocker therapy compared with placebo, but the effects of atenolol and metoprolol were equivalent. beta-Blocker therapy increased cardiac vagal activity, as shown by measures of high-frequency heart rate variability and reflex studies. Lipophilic and hydrophilic beta-blockers appeared to be equally efficacious in increasing the cardiac vagal modulation of heart rate.

Generic health instruments do not comprehensively capture patient perceived improvement in patients with carpal tunnel syndrome.

OBJECTIVE: To assess the sensitivity to change of general quality of life indices in patients with rheumatic diseases, we assessed the performance of 4 instruments in patients with carpal tunnel syndrome (CTS) treated with local injection of corticosteroid. METHODS: We administered visual analog scales (VAS) incorporating measures of overall well being, discomfort, frequency of symptoms, and physical activity; 2 generic instruments [the Nottingham Health Profile (NHP), the Medical Outcomes Study 36 Item Short Form (SF-36)]; and a rheumatoid arthritis-specific instrument, the modified Health Assessment Questionnaire, at baseline and one month after injection. We assessed 30 patients. RESULTS: VAS were significantly better at determining improvement than the generic instruments or the arthritis specific instrument. For the generic scales, only the pain scales of NHP and SF-36 showed moderate or greater change using standardized response means. CONCLUSION: These results suggest that standard tools may not be sufficiently sensitive to show clinically significant change in this common rheumatological problem.