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Rheumatology Advance Access published online on April 4, 2008
Rheumatology, doi:10.1093/rheumatology/ken057
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© The Author 2008. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Rheumatoid arthritis patients who smoke have a higher need for DMARDs and feel worse, but they do not have more joint damage than non-smokers of the same serological group

G. Westhoff1, R. Rau2 and A. Zink1

1Epidemiology Unit, German Rheumatism Research Centre, Berlin and 2Evangelisches Fachkrankenhaus Ratingen, Ratingen, Germany.

Correspondence to: G. Westhoff, Epidemiology Unit, German Rheumatism Research Centre Berlin, Charitéplatz 1, 10117 Berlin, Germany. E-mail: Westhoff{at}drfz.de


   Abstract
Top
 Abstract
Introduction
 Patients and methods
 Results
 Discussion
 Acknowledgements
 Reference
 
Objectives. To investigate the influence of smoking on disease activity, drug need and radiographic joint damage in RF-positive and -negative patients with early RA.

Methods. Baseline and 3-yr follow-up data of 896 patients of an early RA cohort comprised clinical and radiographic parameters (Ratingen Score). Information about disease severity, treatment and smoking were obtained by questionnaires. Univariate and multivariate analyses were used to show the influence of smoking on drug use, ACR improvement and joint damage. Smokers and non-smokers were compared according to RF serology.

Results. Fifty per cent of the patients were never, 23% past and 27% current smokers. Current smokers were significantly more often RF-positive (71%) than past (66%) or never smokers (53%), but neither the RF-positive nor the RF-negative current smokers had higher 28-joint disease activity score (DAS28) or radiographic scores than never or past smokers. Within 3 yrs, current smokers had taken significantly more DMARD combinations or biologics. Non-smokers and those with <20 pack-years (PYs) had a 2-fold higher probability to reach ACR improvement than heavy smokers (>20 PYs). However, smokers did not differ in radiographic joint damage when compared with non-smokers of the same serological group.

Conclusions. The higher use of DMARDs may indicate that smoking weakens the potency of anti-rheumatic drugs and/or is needed to control an otherwise higher disease activity. Since the risk of adverse events increases with the amount of drugs taken, this is another reason to persuade RA patients to quit smoking.

KEY WORDS: Rheumatoid arthritis, Rheumatoid factor, Smoking, Pack-years, Anti-rheumatic drugs, Disease-modifying anti-rheumatic drugs, Disease activity, Radiographic erosion, Joint damage, Outcome


   Introduction
Top
 Abstract
 Introduction
Patients and methods
 Results
 Discussion
 Acknowledgements
 Reference
 
It is well established that cigarette smoking is associated with the production of RF or anti-cyclic citrullinated peptide autoantibodies (anti-CCP Abs) and that it is a risk factor for the development of RA [1–6].

However, results on the influence of smoking on outcome in RA are less consistent. While it is undisputed that RA patients who smoke are more likely to exhibit extra-articular features such as rheumatoid nodules [7–9], lung disease [10, 11] and vasculitis [12, 13] results on disease activity, functional capacity and especially on radiographic joint damage are still rare and rather inconsistent.

Several authors (Saag et al. [14], Wolfe [15], Mattey et al. [16]) have reported that heavy smoking was associated with either a higher prevalence of erosions or higher radiographic scores. However, in Wolfe's cohort, the effect could only be detected by non-linear models and only in patients with a very long smoking history, and in Saag's cohort, the association between smoking and radiographic score disappeared when the RF was considered. Furthermore, no effect was seen at all in the European Norfolk Arthritis Register (NOAR) inception cohort of patients with inflammatory arthritis [7]. In this study, smokers had a higher risk for the development of rheumatoid nodules, but were less likely to have persistent synovitis. Moreover, smoking seemed to be protective against the development of joint damage. The authors, therefore, suggested that smoking may simultaneously have two conflicting influences on disease outcome: a detrimental influence mediated by RF, and also an as yet unexplained protective effect. Similar results have been reported by Finckh et al. [17]. In their prospective cohort, joint damage progressed at a similar rate in current smokers and non-smokers. They even found a significantly reduced progression rate in heavy smokers compared with non- or moderate smokers. Like Forslind et al. [18], who investigated the influence of anti-CCP Ab on radiographic outcome and also could not show that smoking influenced radiographic progression, Finckh et al. [17] consider smoking as a potential risk factor for the initiation of RA, but not on the perpetuation of the erosive process. Moreover, based on findings on the inverse association between smoking and OA [19] or ulcerative colitis [20] and in conjunction with experimental models that demonstrated inhibitory effects of nicotine in endothelial cells [21, 22] Finckh et al. [17] discuss the possibility that heavy nicotine intake may even have anti-inflammatory effects on the erosive process in RA.

Despite the fact that various studies have covered different RA populations, with respect to sample size, disease duration and the proportion of seropositive patients, and in spite of the differences in the measured effects, it seems at least unlikely that smoking has dramatic effects on joint destruction. Wolfe commented that smokers appear to have more severe but not more active RA. Taking advantage of a large early RA cohort, we investigated whether smoking influences disease activity or joint destruction and whether this is reflected by a higher need for anti-rheumatic drugs.


   Patients and methods
Top
 Abstract
 Introduction
 Patients and methods
Results
 Discussion
 Acknowledgements
 Reference
 
From January 2000 through June 2001, 1023 patients with recent-onset RA (according to the revised ACR criteria [23], age ≥18 yrs, disease duration <24 months) were consecutively enrolled in a prospective observational study by 54 rheumatological outpatient facilities in Germany. Baseline and 3-yr clinical examinations included disease activity measurements and radiographs of hands, wrists and forefeet. A biannual patient questionnaire covered type of healthcare, drug use and disease severity.

The RF was assessed by the types of tests that were common in the cooperating care facilities, which was almost always the laser nephelometry technique, measuring the combined amounts of IgM-, IgA- and IgG-RF. Results were reported as positive or negative according to the laboratory's definition.

Radiographic joint damage was assessed by the Ratingen Score (RS) method [24] that evaluates 38 joints separately (posterior–anterior view; all proximal IP and MCP joints, four sites in the wrists, IP joints of the great toes and MTPs 2–5). The amount of joint surface destruction is graded on a 0–5 scale for each joint, providing a maximum score of 190. Each grade represents 20% of the joint surface destruction. All radiographs were scored in sequential order by one investigator (R.R.), who was blinded to all clinical data.

The use of DMARDs, glucocorticoids, NSAIDs and analgesics was reported by the rheumatologist at study entry and at 3 yrs, and also by the patients during the interim (‘no/at regular basis/occasionally’). To enhance accuracy, all common trade names were given in the patient's questionnaire.

Disease activity was assessed by ESR (mm/1 h), CRP (mg/l) and the 28-joint disease activity score (DAS28) [25].

Self-reported global health and pain were assessed by numerical rating scales (NRS 0–10). Functional capacity was assessed by the Hanover Functional Status Questionnaire (FFbH) [26], a self-administered questionnaire similar to and highly correlated with (r = 0.89) the HAQ.

Comorbidity and BMI were assessed by the physician at study entry and after 3 yrs by means of a list of 24 common diseases and body length and weight.

Information on smoking behaviour was enquired from the patient at disease onset and after 1 yr. Further information was gathered after 3 yrs. It comprised the age at the beginning of regular smoking, intermission and total years smoked as well as the average daily number of cigarettes currently smoked and in the past.

The medical ethics committee of the Charité Medical School, Berlin, approved this study and all patients gave written informed consent before entering the study.

Statistics
Genetic and immunological findings support the assumption that RF-positive and -negative RA are differently triggered diseases that are probably also differently driven by tobacco exposure [17, 27, 28]. Therefore, patients were distinguished according to their baseline RF and their smoking behaviour. Descriptive statistics were used to show the association between smoking and baseline as well as outcome measures. Baseline measures were related to the smoking categories ‘currently smoking’ and ‘currently not smoking’. Outcome measures were related to the categories ‘never’, ‘quit before onset’ and ‘ongoing smoking’ or to the cumulative exposure, calculated as pack-years (PYs), with one PY representing the equivalent of 20 cigarettes smoked per day for 1 yr. The 28 seropositive and 13 seronegative patients who had stopped smoking after disease onset were excluded when the outcome was related to current smoking status, but not when it was related to the cumulative smoking dose. The 41 patients were heterogeneous in the time when they had stopped smoking, but were rather homogeneous in the high number of comorbid conditions.

As disease duration varied somewhat and the radiographs were not always taken exactly at study entry and after 3 yrs (mean time span 37.2 ± 6.3 months, median 37), the radiographic progression was adjusted by the individual time span between entry and end point radiographs (Progression rate = Progression/months between T0 and T1 radiographs x 37). The mean adjusted progression rate was almost identical to the unadjusted one (2.73 ± 6.5/2.67 ± 6.5).

Descriptive statistics were used to show the associations between smoking (status and PYs) and outcomes according to the definitions of the ACR [29] improvement criteria and the European League Against Rheumatism (EULAR) response criteria [30]. Multivariate logistic regression techniques were applied to investigate the association between smoking and ACR 20, 50 and 70% improvement. Patients with <10, 10–20 and >20 PYs smoked were compared with never smokers, adjusting for age, sex, baseline DAS28 and RF.

The influence of smoking on joint damage was investigated accordingly, with an RS ≥7 as dependent variable in the multivariate analysis. This cut-off exceeds the minimal detectable change (6.2) of the RS method [24] and covered about one-third of the patients at 3-yrs. To consider the variance in disease duration, the time span between disease onset and T1 radiographs was considered as linear covariate. To investigate whether the lifetime smoking dose (PYs) and/or the current smoking status determined radiographic outcome, a further multivariate regression analysis was performed with a variable combining smoking status and PYs (former smokers </>20 PYs, current smokers </>20 PYs vs never smokers).

All analyses, except for joint damage, were done in the 896 completers. Baseline analyses regarding the association between smoking and joint damage were done in 887 patients with respective T0 radiographs and follow-up analyses were done in 753 patients also providing T1 radiographs.

Statistical analyses were done using SPSS 14.0 statistical software.


   Results
Top
 Abstract
 Introduction
 Patients and methods
 Results
Discussion
 Acknowledgements
 Reference
 
Patient's characteristics at baseline
At disease onset, half of the 896 patients had never smoked; 23% had stopped smoking before disease onset and 27% smoked at disease onset an average of 14 ± 7 cigarettes per day. Past smokers were ex-smokers for an average of 17 ± 12 yrs; only 20% had smoked within 5 yrs prior to disease onset. Men and women differed significantly, as 59% of the women and 28% of the men had never smoked. Patients who smoked at disease onset were significantly younger, better educated, had less comorbid conditions and were significantly more often RF-positive than non-smokers. They did not differ in disease activity and functional capacity, but they did rate their pain significantly worse and already had significantly more often DMARD combination therapies and NSAIDs on a daily basis. Their radiographic scores (RS) were lower than those of the non- smokers (Table 1). According to a multivariate logistic regression analysis covering all the respective parameters, smokers had a 2-fold risk to be RF-positive [odds ratio (OR) 2.0; 95% CI 1.5, 2.7: P = 0.000].


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  		TABLE 1. Baseline characteristics of patients who were smoking/not smoking at disease onset

 
Smoking and RF in men and women
Rheumatoid factor positivity at study entry was strongly dependent on smoking behaviour and gender. Smokers, especially smoking men, were significantly more often RF-positive than men who had never smoked (81.6 vs 45.0%). This was independent of the daily dose smoked. The overall proportion of seropositive patients remained stable at 61% within 3 yrs, but RF-conversion and -reversion differed between smokers and non-smokers. While seropositivity slightly decreased in never (53–51%) and past smokers (66–62%) and also in the 41 patients who had stopped smoking within the observation period (68–63%), it increased in ongoing smokers (72–78%).

Drug therapy in smokers and non-smokers
The overall proportion of patients taking DMARDs decreased from 95% to 82% within 3 yrs. At 3 yrs, the proportions of patients having a DMARD combination or ever having had biologics were higher in current than in never smokers of both serological groups and highest in seropositive current smokers. Smokers had also taken significantly more different DMARDs during the observation period, and the mean glucocorticoid dose of seropositive smokers was higher than that of never smokers. The use of NSAIDs showed the same trend, but did not attain significance (Table 2). There were no associations between RF or smoking and the use of analgesics. As a whole, similar associations were also seen with PYs smoked, but on a somewhat lower level.


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  		TABLE 2. Smoking, RF and drug therapy after 3 yrs

 
Outcome in smokers and non-smokers
At 3 yrs, current smokers of both serological groups had slightly worse outcomes than never smokers of the same serological group (Table 3). The differences were rather restricted to self-reported parameters and they were more evident in seronegative than in seropositive patients. If the 28 seropositive and the 13 seronegative patients who had quit smoking since disease onset would have been left in the equation, differences would have attained statistical significance, since these patients rated their symptoms as the worst (data not shown). Since increasing age usually implies a growing number of comorbid conditions and since the never smokers were significantly older than current smokers (61.5 vs 53.7 yrs at T1), a reciprocal association could have been expected at least in the age-dependent function and general health variables. However, the current smoking status did not correspond to CRP or to ESR titres (data not shown), but rather the cumulative smoking dose (PYs). Seropositive patients with >20 PYs had higher CRP levels than seropositive patients with <20 PYs (13.4 vs 9.4 mg/l). A similar relation was seen in seronegative patients (9.8 vs 6.0 mg/l). The same applied to ESR (24.2 vs 21.2 mm/h in seropositive and 19.6 vs 16.1 mm/h in seronegative patients). Extra-articular manifestations were higher in seropositive patients but not associated with smoking.


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  		TABLE 3. The 3 yr outcomes in RF-positive and -negative patients by smoking

 
At 3 yrs, an association between the current smoking status and ACR 20, 50 and 70% improvement was seen. This association was evident in both serological groups, but did not attain statistical significance (data not shown). Significant differences, however, were detected when the accumulated smoking dose was implemented. Even though the improvement rates did not follow a straight linearity, it was evident that patients with >20 PYs [68% of them current smokers and younger than never smokers (59.8 vs 61.5 yrs)] had the lowest improvement rates in both serological groups (Table 4). This was confirmed with respect to the EULAR response criteria. Smokers with >20 PYs attained less frequently ‘good response’ than never smokers (25 vs 33%) or smokers with <20 PYs (35%). Again, this was seen in both serological groups.


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  		TABLE 4. PYs and ACR improvement in RF-positive and -negative patients by smoking

 
Multivariate logistic regression analyses revealed that never smokers and patients with <20 PYs, independent of whether they had hardly smoked or had accumulated almost 20 PYs, had highly significant higher probabilities to reach an ACR 20% improvement than patients >20 PYs. This was independent of age, RF, baseline CRP, number of comorbid conditions and whether they were current, ex- or never smokers (all of which had no influence on whether ACR 20% improvement was reached). Men compared with women and patients with a higher baseline DAS28 also had significantly higher probabilities for reaching the ACR 20% improvement (Table 5). Almost identical results, apart from even higher ORs for men, were revealed with respect to ACR50% and ACR70% improvement (ACR50%: men vs women = OR 1.8/ACR70%: OR = 2.6; data not shown).


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  		TABLE 5. Adjusted ORs for ACR 20% improvement

 
Smoking and joint damage
The 3 yr total RS and 3 yr progression rate of the 753 patients with T0 and T1 radiographs were independent of sex and positively associated with RF, current smoking status and slightly associated with PYs smoked (Table 6). The radiographic scores were also significantly associated with T1 CRP titres (data not shown) and disease activity (DAS28 < 3.2 RS = 4.4, DAS28 3.2–5.1 RS = 6.1 and DAS28 > 5.1 RS = 9.8) and they were inversely associated with BMI (BMI < 25 RS = 7.0, BMI 25–30 RS = 5.9 and BMI >30 RS = 3.8). The highly significant association between BMI and joint damage in this cohort was reported elsewhere [31].


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  		TABLE 6. Radiographic score and radiographic progression at 3 yrs

 
The rather weak association between smoking and joint damage vanished, when the patients with different smoking habits were compared within their serological group. In fact, seropositive never smokers had higher total RS than seronegative current smokers [6.8 ± 9.2 (95% CI 5.5, 8.1) vs 4.4 ± 6.0 (2.6, 6.2)] or than seronegative patients with >20 PYs smoked [4.4 ± 5.3 (3.0, 5.8)]. The same applied with regard to the progression rate [2.8 ± 5.8 (2.0, 3.5) vs 1.8 ± 4.2 (0.5, 3.0) and 1.8 ± 3.9 (0.8, 2.8), respectively]. The 23 heavy smokers (>20 cigarettes per day) did not differ from moderate smokers or never smokers.

Several multivariate logistic regression analyses did not show an influence of smoking on radiographic outcome; no matter which cut-off was chosen as dependent variable (RS >3 to >10) or how smoking was calibrated as an independent variable (current vs never smokers; past vs never smoker; or a combination of smoking status and PYs: former smokers </>20 PYs, current smokers </>20 PYs vs never smokers). Covariates in the logistic regression equation were gender, age and disease duration (months). The number of comorbid conditions had no influence and was omitted in the final analysis. The only significantly worsening influences were male gender (OR 1.6; 95% CI 1.1, 2.3), RF seropositivity (OR 1.6; 95% CI 1.1, 2.4), elevated CRP (≥15 vs <5 mg/l: OR 2.6; 95% CI 1.2, 4.3) and DAS28 (≥5.1 vs <3.2: OR 1.9; 95% CI 1.1, 3.1), disease duration (OR 1.03; 95% CI 1.01, 1.05/month) and a BMI <25 compared with ≥30 (OR 2.6; 95% CI 1.5, 4.4).


   Discussion
Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
Acknowledgements
 Reference
 
Smoking is the best-known environmental risk factor for seropositive RA and can be reasonably regarded as a contributory cause [32]. According to del Puente et al. [33], the presence of RF in a healthy person poses a risk that the person may develop the disease later in life. In our study of patients with established RA, the most evident differences between smokers and non-smokers were the smokers’ higher proportion of RF seropositivity and their higher need for DMARDs.

Unlike Saag et al. [14], Wolfe [15] and Mattey et al. [16] we did not find that smoking had an effect on joint damage. We also could not find a protective effect of smoking on the number of swollen joints, as observed in the NOAR [7] or in the Swiss prospective cohort [17]. However, the effect of smoking on joint damage in Wolfe's study was only detected in patients with very long smoking histories, and in Saag's cohort the association was driven by the association between RF and joint damage. Unfortunately, we cannot refer to anti CCP-antibodies, since ascertainment was not a routine practice at inception of this cohort.

We could show, in accordance with the aforementioned studies that smokers of both serological groups appear to have a slightly more severe disease presentation. However, the differences between current and never smokers of the same serological group were rather small and did not follow a straight linearity with increasing exposure. However, pain ratings were highest and response rates were worst in patients with the highest smoking exposure.

As in other studies, the associations between smoking and outcome were highly dependent on what types of smoking categories were used. We could show that the current smoking status produces confusing results, since past smokers can obviously not be considered as a group ‘somewhere between never and current smokers’. This pertains in particular to those who stopped smoking after disease onset. These 41 patients had the highest T0 and T1 DAS28, the highest baseline CRP- and ESR levels, the most severe pain and the highest number of comorbid conditions when compared with never, ex- and present smokers. This suggests that they had stopped smoking due to relevant health problems. By entering the ex-smoker category, they shifted the most unfavourable outcomes from the group of smokers to that of the ex-smokers. This reasoning provides the most likely explanation why the alterable current smoking status differentiates less than the unalterable cumulated dose (PYs). However, PYs are also afflicted by changes of smoking habits over times, which may cause statistical problems, too. Since it is uncommon now for older women to start smoking, never smokers constitute a group of above-average age. This is also true for those with many PYs, who are older because it needs time to accumulate a considerable number of PYs. This explains why never and long-time smokers have higher age and numbers of comorbid conditions in common, while current smokers are younger and still of better health, which is reflected in several outcome parameters.

This trend applies to most of the outcome parameters, but not to the need for anti-rheumatic drugs. Even though drug use was positively associated to PYs smoked, it was highest in current smokers. This fact may indicate that former as well as current smoking contributes to higher drug need compared with never smoking. Since other studies did not focus on this question, and Finckh et al. [17] did not find a difference between smokers and non-smokers with respect to drug use, our results are the first to show this association.

The higher drug need may be driven by the smokers’ more severe pain. This association was reported repeatedly [34–38], particularly in musculoskeletal disorders. Some of the studies focus on whether smoking has a deleterious effect on chondrocyte structures by inhibiting cell proliferation and extracellular matrix synthesis. But results vary between deleterious and protective effects of smoking, depending on whether cartilage damage was measured in animal models, in vitro, with magnetic resonance tomography or X-ray, cross-sectionally or longitudinally [34, 39]. However, explanations on why smoking is associated with more severe pain are still lacking. Since cartilage does not have pain fibres, the higher pain is unlikely due to the relationship of smoking and cartilage damage. Results of Finckh et al.' s [17] and our study do not support an influence of smoking on joint damage, at least not on bony structures. It therefore seems implausible that more severe structural damage would have caused the higher pain in smokers. Explanations beyond structural damage seem more likely. They discuss nicotine as a psychostimulant that could affect the manner in which the brain processes sensory stimuli, influencing the threshold of pain tolerance [38]. However, results on pain tolerance of smokers and non-smokers are conflicting, too [40].

At least the higher drug use may be explained by an influence of smoking on basal metabolic rate (BMR). Metsios [41] has recently shown that systemic inflammation in RA causes an elevated BMR due to hypercatabolism and that smoking further incrementally increases BMR. These contributing phenomena seem likely to shorten the bioavailability of anti-rheumatic drugs by an accelerated BMR.

However, the most contradictory result to ours is the missing association between smoking and seropositivity in the Swiss cohort. We, as well as others, found highly significant associations between smoking and seropositivity as well as between seropositivity and outcome [4, 8, 42]. The extraordinary high proportion of seropositive patients in the Swiss cohort may explain why no statistical associations between smoking and RF serology and between RF serology and outcome parameters were found.

In turn, due to a very small number of heavy smokers in our cohort, we could not answer whether heavy smoking has a beneficial effect on radiographic progression. Only three patients indicated smoking >30 cigarettes a day. The 23 heaviest smokers (>20 cigarettes per day) had significantly more often used DMARD combinations (60 vs 28%) or biological therapies (28 vs 7%), but showed neither a benefit of smoking nor of escalated therapies on joint damage.

Joint damage and progression rate in our cohort followed the well-known association between inflammatory variables and radiographic outcome [43, 44], but also showed a strong influence of the BMI. Even though smokers were less frequently obese, the influence of BMI was independent of smoking and the established risk factors for joint damage. The possible mechanisms of how body fat may ameliorate joint destruction in RA, are not yet understood and hypotheses are discussed elsewhere [31, 45, 46]. Since BMI definitely had an influence on joint damage in our cohort, and smoking without much doubt had none, at least the BMI should not be neglected in any investigation on joint damage in RA.

However, this does not nullify the perceived influence of smoking. We can ascertain from our study that smoking is associated with RF positivity, disease severity and higher drug use. Due to confounding by indication we cannot rule out that smokers would have had more erosion, had they not taken more DMARDs and biologicals. There is reason enough for everybody not to smoke. Given the adverse health consequences and the additional risks of side-effects associated with escalated therapies, patients depending on medications should quit all the more so.

Formula


   Acknowledgements
Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 Acknowledgements
Reference
 
The authors wish to thank those rheumatologists who enrolled at least 15 patients each: S. Wassenberg, Ratingen; M. Hammer, Sendenhorst; W. Demary and U. von Hinüber, Hildesheim; F. Hamann and A. Teich, Leipzig; K.L. Schmidt, Bad Nauheim; E. Gromnica-Ihle, Berlin; G. Hein, Jena; R. Haux, Berlin; R. Dreher, Bad Kreuznach; D. Pick, Grafschaft-Holzweiler; M. Stoyanova-Scholz, Duisburg; H. Menninger, Bad Abbach, H. Zeidler, Hannover, H.E. Schröder, Dresden; M. Braun, Cuxhaven; J. Braun, Herne; J. Lautenschläger, Bad Pyrmont; B. Lang, Baden-Baden; A. Thiele, Wuppertal; L. Gross, Bad Bramstedt.

Funding: The study was funded by the German Federal Ministry of Research within the Competence Network Rheumatology (1999–2005).

Disclosure statement: The authors have declared no conflicts of interest.


   Reference
Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 Acknowledgements
 Reference
 

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Submitted 31 August 2007; revised version accepted 24 January 2008.
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D. L. MATTEY, A. BROWNFIELD, and P. T. DAWES
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