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and Dr. MajorM.Ash,Jr. Asa graduatestudentatthe University of Michigan, and later as a colleague andfriend, I had the opportunity to observe the unique talents,contributions, and collaboration of these two individuals.Whenrecently invited to write this article for "Discovery!",it occurred to methat manypeople do not knowhowSig

Despite major advances in caries prevention, a large subset of the U.S. population still needs additional control measures. In numerous other countries, needs are escalating as caries rates continue to rise. Building on current strategies and new insights into the specific mechanisms of caries initiation, researchers are creatively using a variety of new technologies, especially in molecular biology, to fashion a new generation of preventive measures.

The practice of biological science has changed dramatically since mid-century, reshaped not only by a rapid series of landmark discoveries, but also by governmental directives, institutional policies, and public attitudes. Until 1964, the major influences were the mentor, who provided direction and indoctrination into the culture of science, and in dentistry, the newly established NIDR, which fueled the research engine with an expanding research and training program. The 1965-74 period witnessed the advent of the Institutional Review Board, an increased social involvement of biological scientists, and a recognition of the need for biological and physical safeguards in the conduct of research. The most turbulent years were 1975-89, when there was a confluence of animal rights activism and regulation, growing concerns with scientific fraud and publication malpractice, and the stresses and strains (and opportunities) resulting from the rapid expansion of the academic-industrial complex. The current period is characterized by rapid pace, high volume, and an increased depth and breadth of knowledge-a major change in scale in the conduct of science. It is an exciting time but one in which ethical issues are multiplying. Attention must be paid.

Our earlier work demonstrated that the sweetener sucralose, C12 H19 CI3 O8, mixed with water had no effect on intraoral plaque pH. The current study compared the effect on resting plaque pH of sucralose to sucrose when these sweeteners were used in hot coffee at equivalent sweetness levels. Twelve subjects with an identified acidogenic plaque were tested at dicrete sessions, using coffee as vehicle with: (1) sucrose; (2) sucralose; (3) sucralose plus maltodextrin (SM); (4) sucralose plus dextrose and maltodextrin (SMD), and (5) no additional sweetener. Each subject rinsed for 1 min with the test rinse, expectorated, and plaque pH was measured at six dental sites for 60 min using an antimony touch electrode method. Data were summarized for baseline pH, delta pH (baseline pH minus lowest pH attained), minimum pH, and area under the pH curve (AUC). Baseline pH was not different throughout all tests. Quantification of AUC in the various groups showed that sucralose with coffee had no statistically significant impact on plaque acidogenesis. AUC, minimum pH and delta pH were least changed by coffee and sucralose, while the SM and SMD combinations generally led to intermediate changes as compared with coffee sweetened with sucrose or sucralose. Because of its acidic nature, unsweetened coffee led to a modest pH depression, the effect of which appears to be blunted by sucralose. This study confirms that sucralose is non-acidogenic and indicates that sucralose may reduce the acidogenic potential of coffee.

Does reduction of supragingival calculus provide only a cosmetic effect, or does it benefit oral health as well? The author discusses the causes and effects of calculus development and reviews methods of calculus control.

Why are some people more resistant to dental caries than others? Certainly diet plays a part, but are there hereditary factors that affect caries development? This report explores genetic components that appear related to caries resistance and susceptibility.

Dr. Mandel looks at dubious theories from dentistry’s past and questions some practices on the horizon. Instances of dental quackery are easy to spot in history, but what qualifies as quackery in contemporary dentistry? A historical perspective leads to an evaluation of questionable practices in the field today.

The past 50 years of salivary research has been marked by a series of changing perceptions as new techniques and technologies have illuminated the complexities of the secretory mechanism, salivary composition, and function. The modem era began with the innovations of electrophoresis, chromatography, histochemistry, immunochemistry, electron microscopy, and microphysiology. The idea of saliva as primarily a digestive fluid composed of salts, amylase, and mucin was rapidly broadened to encompass a wide spectrum of protective proteins with the dual responsibility of protecting both hard and soft tissues. Characterization of the secretory IgA and nonimmunological antibacterial systems and the proteins responsible for the regulation of calcium and phosphate levels dominated the research in the 1960s and 1970s. An appreciation of the nature, formation, and role of the salivary pellicle and the interplay between bacterial adherence and agglutination provided a clinical thrust. Morphologists and physiologists redefined the secretory process on a molecular level. The 1980s saw the union of structure and function, both in terms of synthesis and release of the secretory products and their specific roles in the oral cavity in health and disease. The excitement of the 1990s is in the genetic control of processes and products, elucidating the mechanisms, and using the information to improve on nature: an era of great expectations and hubris. This article is essentially a personal guided tour through the past 50 years of salivary research.

This report deals with one aspect of tooth permeability, namely, the introduction of a foreign substance into the calcified dental tissues. Primarily its purpose is the development of a new method for studying this phenomenon, utilizing sodium iodide as the foreign substance. Investigation in tooth permeability, especially with regard to enamel, has considered two aspects of the problem-penetration from the pulp outward to the external surface, and from without, inward. The methods employed in these studies included: Various staining solutions applied to the whole tooth in vitro (1), (2). Complex dyes inserted into the pulp and applied to the enamel surface in vivo (3), (4). Introduction of radioactive salts in vitro and in vivo (6, 7, 8, 9, 10). These procedures have provided considerable data on the subject, but are nevertheless open to criticisms. Results published on the basis of experimentation with extracted teeth can be considered only an indication of the true picture because loss of vitality has been shown to influence permeability (3). Investigators using dyes in direct contact with the teeth, for the most part, have employed complex molecular dyes. Since permeability depends largely on the size and charge of the molecule, results obtained from the use of these dyes cannot be applied to calcium, phosphorous, fluorine, and other small inorganic ions which bathe the teeth in vivo. Neither the use of extracted teeth nor dyes contacting the teeth can be correlated with normal physiological conditions. The use of radioactive isotopes, while an excellent method of investigation, requires extensive equipment, is a difficult procedure, and does not clearly demonstrate the distribution of the introduced substance. It has nevertheless contributed much information concerning the degree of tooth permeability in vivo. Wasserman and Blayney (5, 6), Volker and Sognnaes (7, 10), and Barnum and Armstrong (9) have demonstrated that radioactive phosphorous injected intraperitoneally or intravenously finds its way into the dentin and enamel of the teeth. The dentin, as might be expected, takes up considerably more phosphorous than the enamel. All investigators agree that the phosphorous which finds its way into the dentin does so through the blood. As far as the enamel is

Parotid flow rate and chemistry of 78 HIV + gay/bisexual men and 27 HIV-gay/bisexual controls were compared on a longitudinal basis at 4-month intervals over a 1 yr period for changes indicative of inflammatory or autoimmune diseases of the salivary glands, or reduced protective capacity toward oral opportunistic infection. Parotid saliva was examined for concentrations of sodium, chloride, phosphate, total protein, lysozyme, lactoferrin, secretory IgA, salivary peroxidase, histatin and albumin. Chloride, lysozyme and peroxidase were significantly higher in HIV + at all 3 examinations and increased in concentration over time. Although mean values for stimulated flow rate were not significantly different in the two groups over the year, there was a significant increase in the number of HIV + with reduced flow over time. In 6% of HIV + there was a marked reduction in flow rate and Sjögren's syndrome-like elevations in parotid chemistry but no enlargement. At all examinations low flow rate was significantly related to oral candidiasis; T4 levels were inversely related to oral candidiasis, but not to concentration of salivary components or flow rate; nor was AZT use. As a group the HIV + patients maintained normal flow rate and secreted normal or elevated concentrations of protective proteins. A subgroup, however, exhibited diminished flow over time and an increasing tendency to oral candidiasis and a diminution in output of histatins.

Although mercury vapor in high concentration can have deleterious effects on several organ systems, there is no evidence of risk at the levels generated by chewing with amalgam restorations. Epidemiological studies relating amalgam exposure to health outcomes are recommended, however, to provide the profession and the public a full sense of security.

It is becoming increasingly apparent to investigators and clinicians in a variety of disciplines that saliva has many diagnostic uses and is especially valuable in the young, the old and infirm and in large scale screening and epidemiologic studies. The highly sensitive test procedures that are now commonplace makes it practical to quantitate, despite very low concentrations, a large number of hormones and drugs in saliva. Indeed, all steroids of diagnostic significance in routine clinical endocrinology can now be readily measured in saliva. Drug monitoring can include abusive as well as therapeutic agents. The concordance between anti HIV antibodies in saliva and serum has stimulated application to various other antiviral antibodies as well as to viral antigens per se. Saliva has found use as a diagnostic aid in an increasing number of clinical situations and in systemic diseases that can affect salivary gland function and composition such as Sjögren's syndrome, cystic fibrosis and diseases of the adrenal cortex. The list keeps growing.

Both caries and periodontal disease, as well as many diseases of the mucous membranes, tongue, and salivary glands, are infectious. If left untreated or inadequately treated, they have profound systemic, as well as local, effects. Maintenance of oral health goes beyond the physiological needs of proper nutritional intake and protection of the oral tissues. It also includes protection against oral sources of systemic infection and encompasses a range of social and psychological attributes. The rising expectations of patients in the pursuit of comfort and esthetics has provided evidence of the oral contribution to quality of life. Oral infections and their sequela account for the major portion of annual dental expenditures.

Sucralose is a new type of non-caloric, high-intensity sweetener recently approved for use by the U.S. FDA. Its availability may expand the number of palatable, low-sugar foods and beverages currently on the market. A series of studies has been conducted to assess whether sucralose has cariogenic potential. These include an examination of oral bacterial metabolism, experimental caries in animal models, and the effect of sucralose-containing solutions on human plaque pH in situ. The sum of these studies demonstrates that sucralose is non-cariogenic. Sucralose-based sweeteners that contain bulking ingredients, which allow them to pour and measure more like sugar, do have cariogenic potential due to the presence of added fermentable carbohydrate; however, the data suggest that both the currently marketed sucralose granular and packet products are less cariogenic than sugar. Thus, when used to replace sugar, both sucralose and the tested sucralose-based sweeteners may be useful in the dietary management of caries.

There is a growing appreciation for the use of oral fluid as an easily collected, non-invasive diagnostic medium in a variety of disease states and clinical situations. Dental applications include differential diagnosis of salivary gland disease, caries and periodontal disease activity and susceptibility tests, Candida monitoring and testing for HIV and hepatitis.

Dr. Neil Goldsworthy had a profound effect on. the development of dental research in the biological sciences in Australia, including measures for the prevention of dental caries. He played a major role in the establishment of the Institute of Dental Research in Sydney in 1946 and was Director until his sudden death in 1960. Reviewing the institute's activities provides the opportunity for his achievements to receive due recognition and to show how they influenced its subsequent development. As one who has been associated with the Institute for most of the last 50 years, it is an honor for me to undertake this task.

The multimedia portrayals of dentists and dentistry have expanded in scope. Prevention and esthetics have replaced drilling and extraction in the public perception of dental practice. According to the author, dentists themselves are no longer treated exclusively as buffoons or sadists. Instead, he writes, they are more apt to be seen as solid citizens, occasionally as romantic figures and even as complex, realistic human beings.

Changing views of the pathogenesis and progression of the periodontal diseases and new modalities for treatment have stimulated a plethora of physical, biochemical, microbiologic, and immunologic diagnostic procedures, tests, and devices. Clinical trials address needs for: 1) screening tests and risk assessment for disease susceptibility; 2) identification of active and progressive disease sites; 3) making therapeutic decisions; 4) monitoring therapy; 5) establishing a maintenance schedule; and 6) prognosis assessment. Needs and priorities of general, specialty, and public health practitioners differ. Validation of tests proceeds in a hierarchy of study designs from cross sectional and case control studies to retrospective and prospective longitudinal multi-center trials. For broad-scale application, randomized controlled trials (and eventual meta-analysis) will be required. Design issues are those common to all clinical trials in periodontics plus special considerations depending on type of test and its intended use. For diagnostic tests, recommended surrogate endpoints are attachment and alveolar bone levels-the traditional "gold standards." Validation of diagnostic tests is best accomplished by generation of 2 x 2 contingency tables to calculate sensitivity and specificity, positive and negative predictive values, relative and absolute risks, and odds rations. Each has a place-depending on the clinical situation and needs of the clinician.

The Seal of Acceptance of the American Dental Association's Council on Dental Therapeutics has been awarded to Listerine and chlorhexidine gluconate (Peridex). The mechanism of action of Listerine involves bacterial cell wall destruction, bacterial enzymatic inhibition, and extraction of bacterial lipopolysaccharides. Chlorhexidine has the property of substantivity, i.e. the ability to bind to hard and soft tissue with slow release. Antibacterial mouthrinses/dentifrices containing triclosan hold promise for the reduction of plaque and gingivitis but are not yet available in the United States. The quaternary ammonium compounds and sanguinarine compounds (Viadent) have some merit, but studies of their efficacy in plaque and gingivitis reduction are mixed. New products containing various fluorides and oxygenating agents may have potential for the future as antiplaque and antigingivitis agents.

The effects of smoking, specifically the influence it has on periodontal disease, are reviewed. Since the early 1600s, questions have been raised about the ill effects of smoking. Tobacco has long been linked to oral cancer and leukoplakia, but research in the last 20 years suggests an association with other oral diseases as well. Studies concerning the effects of smoking on the periodontal diseases-and the mechanisms involved-are reviewed.

Dentistry has been portrayed as a high-risk profession in recent reports. A look at several areas of concern, however, shows that the field is no more hazardous than any other profession--and less than most.

In recent years new head shapes and angles, bristle lengths and designs, have flooded the toothbrush market. Are these truly innovations or just gimmicks? Several comparative studies are reviewed.

In the evolution of oral hygiene practices, the toothpick is the progenitor device. Although modern variations are used interdentally, with the current emphasis on plaque control rather than gingival massage and stimulation, the toothpick has been largely superseded by floss, interproximal brushes, and other supplementary aids. The natural hard bristle toothbrush and vigorous scrub brushing popular a generation ago have been replaced by soft bristle nylon brushes and gentler, more defined brushing procedures for plaque removal in the crevicular areas. Quantitative studies support the superiority of the current techniques in maintaining periodontal health with less trauma to the oral tissues.

The lipid content and composition of these pellicles and the effect of lipids on their ability to retard the diffusion of lactic acid were investigated. Lipids accounted for 22.4% of the dry weight of caries-resistant enamel pellicle and 19.2% of caries-resistant cementum pellicle; the pellicle of caries-susceptible enamel contained 24.6% lipids and that of caries-susceptible cementum, 23.4%. Enamel and cementum pellicles from caries-resistant saliva had a significantly lower content of neutral lipids and phospholipids, whereas the glycolipid content was lower, although not significantly, in caries-susceptible pellicles. Pellicles from caries-resistant saliva had a considerably greater capacity to retard lactic acid diffusion than those from caries-susceptible saliva. In all cases, the retardation capacity was clearly dependent upon the lipid constituents, removal of which caused a 50–52% drop in lactic acid impedance by caries-resistant enamel and cementum pellicles, and 32–35% drop by caries-susceptible pellicles. On reacting the delipidated pellicles with their lipids, it was found that, in all cases, the highest quantitative effect on the restoration of the retardation capacity occurred when phospholipids were added. The findings suggest that the events controlling the interaction of salivary phospholipids with enamel and cementum may determine the susceptibility of the tooth surface to demineralization by acids produced by cariogenic micro-organisms.

What we experienced today was an effective fusion of research and clinical application, a comprehensive description of current knowledge of the pathogenesis of periodontal disease and objective methods for its measurement—the state of the science—and how to incorporate this information into dental practice—the state-of-the-art. The program began with an update by Dr. Socransky on the complexities of periodontal microbiology and oral ecology and how the oral bacteria micro-manage their environment, in which we have a very proprietary interest. He stressed the need to consider the host, compatible and beneficial species as well as the destructive agents, and the need to consider the delicate balance between them. Identifying the relatively small number of periodontopathic bacteria is only part of the problem. Current research is focused on identifying the clonai types responsible for virulence, the transmission of virulence factors among organisms, and host susceptibility factors that encourage the virulence factors to be "turned on." Turning to the current clinical application of the laboratory research in microbiology, Dr. Listgarten described the various monitoring techniques that have been studied and the test procedures that have been devised for identifying the most likely periodontopathic bacteria. His conclusions are that the predictive value of either positive or negative tests for selected bacterial species have not proven high enough to date for routine use in clinical practice. Nevertheless, bacteriologie tests have been of value in management of patients with juvenile Periodontitis and refractory forms of periodontal disease. His overall assessment

Fifty 22-month-old male Sprague-Dawley rats were fed for 8 weeks ad libitum with either a 20% protein diet (control) or a 5% protein diet (protein malnourished group). Submandibular glands were removed, weighed and homogenate prepared. After the low protein diet, there was a slight but significant decrease in body weight, glandular content of total protein (mg/g tissue), kallikrein activity/mg protein and glutamine-rich peptide. In contrast, the gland weight, DNA and mucin content were not changed by feeding a low protein diet. Thus in aged rats submandibular glands are only modestly affected by protein malnutrition and the effects on gland-specific proteins vary.

Nature's demands on salivary glands are extensive and diverse and range from the reptilian need for a venomous drop to incapacitate its prey to the 100 quarts that ruminants require to digest a day's grazing. Other species depend on saliva not for survival, but for improving the quality of life, using the fluid for functions varying from grooming and cleansing to nest-building. Humans can manage without saliva; its loss is not life-threatening in any immediate sense, but it results in a variety of difficulties and miseries. Oral digestion per se is only of marginal importance in humans, but saliva is important in preparing food for mastication, for swallowing, and far normal taste perception. Without saliva, mealtimes are difficult, uncomfortable, and embarrassing. The complex mix of salivary constituents provides an effective set of systems for lubricating and protecting the soft and hard tissues. Protection of soft tissues is afforded against desiccation, penetration, ulceration, and potential carcinogens by mucin and anti-proteases. Saliva can encourage soft tissue repair by reducing clotting time and accelerating wound contraction. A major protective function results from the salivary role in maintenance of the ecological balance in the oral cavity via; (1) debridement/lavage; (2) aggregation and reduced adherence by both immunological and nan-immunological means; and (3) direct antibacterial activity. Saliva also possesses antifungal and anti-viral systems. Saliva is effective in maintaining pH in the oral cavity, contributes to the regulation of plaque pH, and helps neutralize reflux acids in the esophagus. Salivary maintenance of tooth integrity is dependent on: (1) mechanical cleansing and carbohydrate clearance; (2) post-eruptive maturation of enamel; (3) regulation of the ionic environment to provide a remineralizing potential without spontaneous precipitation; and (4) pellicle deposition and limitation of acid diffusion. Saliva also plays a role in water balance, can serve in a limited way in excretion, and has possible hormonal function in the gastro-intestinal tract.

The periodontal status of renal transplant patients on immunosuppressant drug therapy was compared with that of an age matched normal group over a period of 2 to 4 1/2 years. Gingival Index, Plaque Index, and Periodontal Destruction Index were used as measures of comparison. Over this period of time the Gingival Index of the immunosuppressed patients increased significantly when compared to the normals. There was a significant increase in the mean Plaque Index for both groups during the study period. The increase was greater in the immunosuppressed group. However, the difference in the Plaque Index for the two groups was not significant. There was little change in the Periodontal Destruction Index in both groups over time. The results of this study indicate that there is little difference in the rate of periodontal destruction between patients taking immunosuppressant drugs and normal patients. These findings, taken in conjunction with other recent reports, would seem to indicate that T cells play a minor role in the etiology of periodontal disease.

Eighteen patients with alcoholic cirrhosis were examined, and parotid saliva was collected. Enlargements of the parotid glands were seen in eleven of the eighteen patients (61%). This percentage is in accord with the data previously reported. The salivary findings of increased flow rate, protein, and amylase levels indicate that hypertrophy and increased acinar function may be a component of the parotid enlargement and that, furthermore, a fatty replacement of functional gland tissue is probably not involved. In addition, the salivary electrolyte changes found, increased potassium with effectively decreased sodium excretion, suggest that the elevated aldosterone level commonly found in cirrhotic patients affects salivary secretions in these patients in much the same way as it does in patients with hypertension.

A method for quantitating lysozyme by using carbamylated antiserum (commercially available) to human lysozyme in a electroimmunodiffusion technique has been developed. The method measures specific protein not lytic activity as the lyso-plate method does. We have applied this method to tears, parotid saliva, submandibular-sublingual saliva, nasal secretions, serum, and minor salivary gland secretions. We specifically selected submandibular-sublingual saliva for a comparison test with the lyso-plate method because of the known mucin content of the submandibular-sublingual saliva. Our findings indicate that no pretreatment is necessary for the electroimmunodiffusion technique. The lysoplate method, on the other hand, requires pretreatment with Tris-acetate pH 4.5 to dissociate the mucin-lysozyme complex and give accurate values.