Interactions between dietary chemicals and human sulfotransferases-molecular mechanisms and clinical significance.

Sulfation plays a major role in the detoxication of xenobiotics as well as in modulating the biological activity of numerous important endogenous chemicals. In contrast to this "chemical defense" function, sulfation is also a key step in the bioactivation of a host of pro-mutagens and pro-carcinogens. These reactions are catalyzed by an expanding family of sulfotransferase (SULT) enzymes, which transfer a sulfuryl moiety from the universal donor 3'-phosphoadenosine 5'-phosphosulfate. Here, we discuss current knowledge of the human sulfotransferase enzyme family, of which at least 11 members have been identified to date, including regulation of expression by endogenous compounds and xenobiotics as well as the molecular basis of polymorphisms in members of the SULT1A (phenol sulfotransferase) family. We also present new data on the inhibition of SULT1A enzymes by dietary chemicals, showing that compounds to which we are exposed regularly, such as epigallocatechin gallate and epicatechin gallate are extremely potent inhibitors of phenol sulfotransferases (K(i) in the nanomolar range for SULT1A1). We found that the mechanism of inhibition by these chemicals varied depending on the individual isoform involved, showing uncompetitive inhibition of SULT1A1 whereas with SULT1A2 and -1A3 they demonstrated mixed type inhibition. Thus, genetic-environmental interactions may play an important role in modulating sulfotransferase activity and in determining individual response to chemicals metabolized by these important enzymes.

The esthetic impact of extraction and nonextraction treatments on Caucasian patients.

This investigation was designed to compare the esthetic effects of extraction and nonextraction treatments. Panels of 58 laypersons and 42 dentists evaluated randomly presented pre- and posttreatment profiles of 70 extraction and 50 nonextraction Class I and II Caucasian patients. The samples were similar at the outset; however, at the end of treatment, the extraction patients' faces were, on average, 1.8 mm "flatter" than the faces of nonextraction subjects. The flatter faces were preferred by both panels, dentists more so than laypersons. In general, nonextraction treatment was seen as having little effect on the profile, whereas the perceived effect of extraction treatment was a statistically significant function of initial soft tissue protrusion-the greater the initial protrusion, the greater the benefit. The point at which a reduction in protrusion produces a perceived improvement was explored by way of regression analysis. Both panels saw extraction as being potentially beneficial when the lips were more protrusive than 2 to 3 mm behind Ricketts' E-plane. It is concluded that extraction treatment can produce improved facial esthetics for many patients who present with some combination of crowding and protrusion.

Expansion with vestibular shields: an experimental test of the periosteal-pull hypothesis.

Two mechanisms are said to be responsible for the expansion commonly produced by buccal shields: (1) unbalanced tongue pressure and (2) periosteal pull; that is, periosteal traction on the bone overlying the molar roots. The present study used 44 young albino rats to examine these two alternatives. Half the rats wore buccal shields to produce molar expansion, and half had their maxillary molar crowns ground down to the gingiva to eliminate the effect of the tongue. In the resulting 2 x 2 design, four experimental groups were formed: (1) SM, shields and intact molars; (2) Sm, shields and reduced molars; (3) sM, no shields and intact molars; and (4) sm, no shields and reduced molars. It was hypothesized that if vestibular shields produce expansion through periosteal traction, the presence or absence of molar crowns should make no difference. Conversely, if the expansion is caused by unbalanced tongue pressure, shields should have an effect only in conjunction with intact maxillary molars. Palatal amalgam implants and dorsoventral cephalograms were used to measure the maxillary basal and dental expansion that occurred during the 6 weeks of the experiment. Analysis of variance showed the presence of highly significant interaction between shields and molars: the shields produced an increase in posterior dental expansion, but only when molar crowns were present. In contrast, basal expansion was unaffected by any combination of treatments. At least for the rat, it may be concluded that unbalanced tongue pressure, rather than periosteal traction, is probably responsible for the expansion produced by buccal shields.

The perceived impact of extraction and nonextraction treatments on matched samples of African American patients.

Orthodontic patients of African descent often seek some measure of reduction in profile protrusion. Lip retraction, however, seems to imply a need for premolar extraction. But in a nonextraction era, what does orthodontics have to offer the bimaxillary protrusion patient? To a considerable extent, it depends on what the patient wants and what treatment can provide. The present study was designed to address these questions by comparing the esthetic impact of extraction and nonextraction therapy on two morphologically similar samples of African American patients with Class I and II malocclusions. In addition to the patients, four panels of judges (black and white orthodontists and black and white laypersons) were asked to compare the pretreatment and posttreatment profile tracings and to quantify their perceptions of the esthetic impact of the change that occurred during treatment. Although there was a strong correlation among the various groups' ratings, there were a number of statistically significant differences. Premolar extraction led to a modest reduction in dental and soft tissue protrusion; nonextraction, by way of contrast, produced an increase. Presumably in response to these changes, all panels, independent of race or education, tended to prefer the posttreatment profiles, especially the posttreatment extraction profiles. There was, however, a significant interaction between race and treatment. The perceived effects of nonextraction treatment were modest and largely unrelated to the pretreatment profile, whereas the impact of premolar extraction was a highly significant function of initial protrusion: convex profiles were improved, but relatively straight profiles were made worse. The various panels, however, differed in their estimate of the point at which a profile might benefit from extraction (ie, profile reduction). For our white panelists, that point was reached when the lower lip was about 2 mm in front of Ricketts' E-plane. For our black panelists, the equilibrium point came at +4 mm. These findings imply that there is significant interaction among the type of treatment, the race of the patient, and both the race and professional background of the observer. Facial beauty, it would seem, is in the hand of the orthodontist, as well as in the eye of the beholder and the face of the beheld.

A retrospective study of two-stage treatment outcomes assessed with two modified PAR indices.

This retrospective study was undertaken to evaluate the long-term outcome of two-stage (functional/fixed) Class II treatment. A modified peer assessment rating (PAR) was applied to the records of 27 patients who had been recalled an average of 9 years after the completion of the second phase of treatment. UK and US weightings were applied. Analysis of variance identified significant differences among treatment stages. The greatest change in PAR score occurred during the first (functional) phase of treatment. By the end of the second phase, there had been an 83% reduction in PAR score. At recall, however, the PAR scores had increased significantly, due largely to relapse in overjet and in the lower labial segment. These results call into question the ultimate utility of early, two-stage treatment regimens. Although the differences between the UK and USA weightings were smaller than anticipated, the nature of the relapse seen here argues against the American exclusion of the lower labial segment.

Long-term comparison of extraction and nonextraction alternatives in matched samples of African American patients.

African American orthodontic patients often present with morphologic characteristics that prompt the extraction of premolars. Referring dentists, however, commonly see extraction as a cause of "dished in" profiles, collapsed arches, and temporomandibular dysfunction. If true, these claims imply that African American patients are disproportionately at risk of clinical misadventure. Unfortunately, a meaningful long-term comparison of alternative treatments--be it retrospective or prospective--requires samples of patients who were equally susceptible to the two alternatives. Thus, if a retrospective study is to be free of susceptibility bias, the samples must be matched with respect to the anatomic differences that prompted the clinicians' choice of treatments. The goals of this investigation, therefore, were the following: to gather a large sample of African American expatients and to identify by means of discriminant analysis the characteristics that seem to have been important to the extraction decision, to use this knowledge to assemble subsamples of extraction and nonextraction expatients (both Class I and II) who were similar before treatment, and, finally, to recall them so that the long-term impact of the two strategies could be compared. In the end, 60 expatients--30 extraction and 30 nonextraction--were recalled, on average, nearly 8 years after the completion of treatment. In general, both treatments reduced irregularity and neither seemed to produce posterior mandibular displacement. Premolar extraction led to a modest reduction in dental and soft tissue protrusion (half the incisor retraction minus one); nonextraction, by way of contrast, produced an increase. Long term, the difference between the two treatments was about 2 mm at the upper lip and 4 mm at the lower. Excessive profile flattening was not a common finding. Our findings thus imply that the various "functional orthodontic" arguments against premolar extraction do not apply to African Americans any more than they do to whites.

Growth and the Class II patient: rendering unto Caesar.

In the context of Class II treatment, most probably would agree that an excess of mandibular growth would be helpful, both to the patient and to the orthodontist. The literature features a smattering of evidence that this is precisely the sort of pattern one sees in many Class II patients, quite independent of treatment strategy. There is, however, a tendency to expect (and perhaps to see) favorable growth only in functional-appliance patients. As a result, growth modification therapy may receive more credit than it deserves in the world of optimistic, albeit uncontrolled, clinical observations and impressions. In the present study, the pattern of sagittal maxillo-mandibular growth and/or displacement ("apical base change") was examined in 120 Class II patients treated with the edgewise appliance. Regardless of treatment (extraction or nonextraction), 9 out of 10 showed a pattern of change in which the mandible advanced relative to the maxilla. It is concluded that an assessment of treatment alternatives, especially those designed to modify growth, must employ this favorable pattern as the baseline from which the effects of growth modification are judged. Methods of factoring out the "good growth" that commonly accompanies fixed-appliance therapy are discussed within the context of evaluating the effects of functional appliances.

Sensitivity of a method for the analysis of facial mobility. I. Vector of displacement.

OBJECTIVE: (1) To determine which facial landmarks show the greatest movement during specific facial animations and (2) to determine the sensitivity of our instrument in using these landmarks to detect putatively abnormal facial movements. DESIGN: Movements of an array of skin-based landmarks on five healthy human subjects (2 men and 3 women; mean age, 27.6 years; range, 26 to 29 years) were observed during the execution of specific facial animations. To investigate the instrument sensitivity, we analyzed facial movements during maximal smile animations in six patients with different types of functional problems. In parallel, a panel was asked to view video recordings of the patients and to rate the degree of motor impairment. Comparisons were made between the panel scores and those of the measurement instrument. RESULTS: Specific regions of the face display movement that is representative of specific animations. During the smile animation, landmarks on the mid- and lower facial regions demonstrated the greatest movement. A similar pattern of movement was seen during the cheek puff animation, except that the infraorbital and chin regions demonstrated minimal movement. For the grimace and eye closure animations, the upper, mid-facial, and upper-lip regions exhibited the greatest movement. During eye opening, the upper and mid-facial regions, excluding the upper lip and cheek, moved the most, and during lip purse, markers on the mid- and lower face demonstrated the most movement. We used the smile-sensitive landmarks to evaluate individuals with functional impairment and found good agreement between instrument rankings based on the data from these landmarks and the panel rankings. CONCLUSION: The present method of three-dimensional tracking has the potential to detect and characterize a range of clinically significant functional deficits.

Measurement of facial soft tissue mobility in man.

OBJECTIVE: The assessment of facial mobility is a key element in the treatment of patients with facial motor deficits. In this study, we explored the utility of a three-dimensional tracking system in the measurement of facial movements. METHODS AND RESULTS: First, the three-dimensional movement of potentially stable facial soft-tissue, headcap, and dental landmarks was measured with respect to a fixed space frame. Based on the assumption that the dental landmarks are stable, their motion during a series of standardized facial animations was subtracted from that of the facial and headcap landmarks to estimate their movement within the face. This residual movement was used to determine which points are relatively stable (< or = 1.5 mm of movement) and which are not (> or = 1.5 mm of movement). Headcap landmarks were found to be suitable as references during smile, cheek puff, and lip purse animations, and during talking. In contrast, skin-based landmarks were unsuitable as references because of their considerable and highly variable movement during facial animation. Second, the facial movements of patients with obvious facial deformities were compared with those of matched controls to characterize the face validity of three-dimensional tracking. In all instances, pictures that appear to be characteristic of the various functional deficits emerged. CONCLUSIONS: Our results argue that tracking instrumentation is a potentially useful tool in the measurement of facial mobility.

Let them eat cake: the struggle between form and substance in orthodontic clinical investigation.

Events of the past decade or so argue that there is little support in the literature for much of the specialty's treatment portfolio. The resulting call for 'evidence-based' treatment (not to mention the obvious intellectual bankruptcy of much of the clinical literature) has prompted many to argue that the randomized clinical trial (RCT) represents the future of orthodontic clinical investigation. The RCT, after all, is medicine's gold standard; what more is there to say? A popular, but ultimately divisive, corollary of this mimicry is the smug tendency to discount all other sources of data. In the face of a need for information, this attitude is also a wasteful conceit: in the end, the RCT can be applied only to a very narrow spectrum of orthodontic questions. Randomization implies equal susceptibility. Any prospective participant would have to be informed of this equality as part of the informed consent process. Unfortunately, it would be nearly impossible to enroll fully-informed subjects into any study whose alternatives are of markedly different morbidity: extraction versus non-extraction or orthodontics versus surgery. Thus, when measured against the most vexing clinical questions, the orthodontic RCT is almost by definition an amusing diversion--expensive, but relatively trivial in scope. Like it or not, it seems reasonable to conclude that most of the specialty's comparative clinical data will have to be generated by way of non-randomized designs in which care is taken to minimize the various known sources of bias. There probably is no other way.

A comparative analysis of Class II treatments: a retrospective/prospective alternative.

Because of a perceived need to examine problems more pressing than 'now versus later' or 'headgear versus functionals', a retrospective/prospective alternative to the randomized clinical trial has been developed. In this approach, discriminant analysis is used to identify samples of ex-patients who, prior to treatment, were equally susceptible to various contemporary treatment alternatives: extraction, non-extraction; orthodontics, surgery; fixed versus functional. This method of 'confounder summarization' has made it possible for us to conduct a wide variety of long-term comparisons and, in the process, to assess treatment efficiency, stability, esthetics, functional impact, and interaction with the pattern of facial growth. These studies are described in broad outline and serve as examples of the type of data that can be generated in a timely fashion by carefully planned, quasi-experimental investigations.

A retrospective comparison of frontal facial dimensions in alveolar-bone-grafted and nongrafted unilateral cleft lip and palate patients.

This retrospective study was undertaken to describe and compare frontal craniofacial dimensions in alveolar-bone-grafted and nongrafted complete unilateral cleft lip and palate (CUCLP) patients and in noncleft subjects with normal occlusions and good facial balance. Clinical data were obtained from the files of the Hospital for Sick Children, Toronto. Patients were eligible for inclusion if they had posteroanterior cephalograms (PA) taken at adulthood and no congenital anomalies other than CUCLP. A total of 86 adult Caucasian CULCP patients were studied, including 58 who had not received grafts, 28 who had received secondary alveolar bone grafts, and, for comparison, 60 noncleft Caucasian adults. The PA cephalometric radiographs were traced, digitized, and measured. Analysis of variance (ANOVA) was used to test for among-groups differences in the means of the ratios, proportions, and angular measures. Tukey-Kramer HSD procedure was used to conduct post-hoc pairwise comparisons following significant (p < or = 0.05) F-ratios from ANOVA. Sexual dimorphism was a common finding, with males demonstrating greater facial width. Despite primary surgical repairs, the anterior nasal spine in the nongrafted CUCLP patients was deviated to the noncleft side, and the alar base was depressed on the cleft side. The maxillary incisors close to the cleft site were irregularly inclined, and this irregularity was more severe in the nongrafted CUCLP patients. The long-term effects of secondary alveolar bone grafting on transverse craniofacial growth appears to be minimal and limited to the immediate area of the cleft.

Balancing the books on orthodontic treatment: an integrated analysis of change.

A method of cephalometric analysis is presented in which molar and overjet corrections are seen as the algebraic sum of facial skeletal growth and tooth movement relative to basal bone. The steps of superimposition and measurement are described, and a means of summarizing these changes--the 'pitchfork diagram'--is suggested.