Download Relations of Oral and Systemic Health and Disease

Copyright 1996, Hill’s Pet Nutrition, Inc. Reprinted with permission from the Proceedings of a Conference on Companion Animal Oral Health,
University of Kansas, Lawrence, March 1-3, 1996, Sponsored by an Educational Grant from Hill’s Pet Nutrition, Inc.
Relations of Oral and Systemic Health and Disease
by John J. Hefferren, Ph.D.
Research Professor
Higuchi Biosciences Center
University of Kansas
Lawrence, KS
Introduction
The mouth is an integral component of the head. The head is connected to the body. This visual linkage stresses the
multidimensional dependency of oral to systemic health and disease.
Linkages in health and disease take many routes from genetics to shared mucosal tissue of the gastrointestinal tract.
This sharing is illustrated in diseases like Crohn’s disease that can occur anywhere in the gastrointestinal tract from
the oral cavity to the anus.1
Although the differences between people, companion animals, and others are recognized, the similarities are many
thereby providing some insight and understanding to each species. Rats have been the animal of choice for human
dental caries studies whereas the dog has been used to model human oral soft tissue studies.2-4 While the cat has
been used less as a dental model, its cousin the ferret has been used for oral soft tissues studies such as gingival
hyperplasia associated with chronic phenytoin therapy.5 Primates have been the preferred human oral disease
model; however, the general cost of this model has precluded its more general use. Similar comments could be made
for the use of pigs for hard tissue and sheep for soft tissue studies, although the anatomical shapes and oral flora
respectfully are comparable to that of people.6
For this paper, the similar response characteristics of human beings and animals are assumed to provide an initial
basis for hypothetical projection to companion animals.
Health vs. Wellness
The World Health Organization 7 has defined health as the state of physical, mental, and social well-being and not
merely the absence of disease or infirmity. Absence of disease is thus no longer equated with health. For this reason,
the quality of life, comfort, and ability to be productive are important considerations that become more important as
life is longer. This is true for human beings and animals. Each needs to contribute to be fulfilled.
The definition of dental care has broadened. Infections of the oral cavity require as much attention as do conditions
in other parts of the body that may have been treated more aggressively in the human medical and veterinary
medical communities. Interdisciplinary teams formed to treat cancer and heart disease or perform transplants are
becoming the rule in human medicine,8 and should be used in veterinary dentistry and medicine where appropriate
and possible. Although most oral conditions other than certain carcinomas may not be fatal in themselves, dental
disease can contribute to a fatal disease complex. It may be even more important to behavioral and social issues with
people and companion animals.
Dietary Choices
Oral conditions such as loose and missing teeth and sore soft tissues can affect the nutrient uptake from foods
consumed. Mastication is more important for meats and vegetables and may be required for nutrient absorption.9
Older people, dogs, and cats are frequently given soft foods to accommodate these oral conditions. This approach
may compromise nutrient availability as well as natural oral exercise and cleansing from foods. Although canned
animal foods are usually nutritionally adequate, most of these foods have little naturally cleansing nor require
physical exercise action.
Xerostomia may make it more difficult to process fibrous foods such as vegetables thus there is often a lower caloric
intake, and often deficiencies in proteins, vitamins A and C, thiamin, and riboflavin.10-12 These vitamins have been
shown to positively affect oral soft tissue health.13 Changes in taste perception are often associated with these
conditions and result in decreased interest in eating.11Modest lowering of salivary fluids can dramatically affect
eating, so that the consistency and fluidity of the food become very important.
Heart Disease
Periodontal and dental disease in general have been associated with and classified as risk factors for heart disease.14
In 1989, Finnish workers reported an association of dental health with cerebral infarction and acute myocardial
infarction in young and middle-aged men.15 In their statistical analysis of the studies, these workers included
traditional risk factors for strokes and heart attacks. They concluded that the associations found could not be
explained by age, social class, smoking, serum lipids or diabetes.16 These investigators used a total dental index to
quantify oral disease much as Dr. Linda DeBowes et al used in their studies relating canine oral (periodontal) and
systemic disease.17 As one might expect, any attempt to quantitate dental disease in people or animals with one
number results in a debate about the index used.
The Finnish studies prompted the re-examination of the national health and nutrition examination study (NHANES)
data. Reviewing the results of 9,760 patient examinations confirmed the conclusions of the Finnish studies linking
coronary artery disease and periodontal disease. In this study, 18 both periodontal disease and poor oral hygiene
were strong indicators of risk of coronary heart disease and stronger indicators of total mortality (Table 1). The risks
of the male population, 25 to 49 years, were adjusted for age, race, gender, education, poverty index, marital status,
systolic blood pressure, total cholesterol, diabetes, body mass index, physical activity, alcohol consumption, and
cigarette smoking. The intermediate value for gingivitis (between no disease and periodontitis) for both coronary
heart disease and total mortality is consistent with the extent of periodontal disease and thus adds to the
persuasiveness of the conclusions.
Table 1
Adjusted Relative Risks for Coronary Heart Disease and for Death from any Other Causes in Men,
25 to 49 Years with Baseline Periodontal Status 18
Periodontal
Status
No.
Coronary Heart
Disease
Total Mortality
No disease
673
1.0
1.0
Gingivitis
529
0.98 (0.63-1.54)*
1.42 (0.84-2.42)
Periodontitis
300
1.72 (1.1-2.68)**
2.12 (1.24-3.62)**
No teeth
92
1.71 (0.93-3.15)
2.60 (1.33-5.07)**
*95% Confidence interval
**Statistically significant
Genco and Loe 19 state that systemic conditions and disorders are now considered secondary factors modulating
disease initiation or progression rather than acting as primary etiological factors. The current emphasis has focused
on systemic conditions and disorders that are risk factors for periodontal disease.
Epidemiological studies designed to relate systemic diseases and periodontal disease have had limited success. One
study of 1,300 hospitalized patients measured alveolar bone loss and correlated these measurements with various
diseases.20 No statistical differences were obtained. Another study classified 4,000 subjects according to dental
disease status which was then correlated to periodontal disease. Comparing malignancies, respiratory, nervous
system, kidney and liver disease, only patients suffering from diabetes had a statistically significant higher
prevalence of periodontal disease than hospitalized control patients.21
Bacterial Endocarditis
The American Heart Association (AHA) has issued recommendations for the prevention of bacterial endocarditis
periodically since 1955. During this period, the Council on Dental Therapeutics has worked with the AHA and copublished recommendations for dentistry. The last report of the Council and the AHA in February 1991 22 is very
specific about those patients with cardiac conditions who require and those who do not require antibiotic
prophylaxis when dental procedures are performed. For example, patients with cardiac conditions who require
antibiotic prophylaxis include those with:
Prosthetic cardiac valves including bioprosthetic and homograft valves
Previous bacterial endocarditis, even in the absence of heart disease
Surgically constructed systemic-pulmonary shunts
Most congenital cardiac malformations
Rheumatic and other acquired valvular dysfunction, even after valve surgery
Hypertrophic cardiomyopathy
Mitral valve prolapse with valvular regurgitation.
Cardiac patients who require dental or oral surgical procedures where endocarditis prophylaxis is
recommended are illustrated by those who need:
Dental procedures likely to induce gingival or mucosal bleeding including professional cleaning
Surgical operations involving respiratory mucosa (maxillary sinus)
Incision and drainage of infected tissue
Intraligamentary injections
One of the most striking characteristics of the Council report on preventing bacterial endocarditis is the inclusion of
a section by Mary K. Logan, J.D., Chief Counsel of the American Dental Association. Ms. Logan states in her
section of the report:
“Some may claim the evidence is lacking to substantiate the need for prophylactic antibiotics with routine dental
procedures on patients with damaged or abnormal heart valves or congenital heart conditions. Others may believe
the responsibility for these conditions rests solely with the patient’s physician.
“None may argue, however, with the simple fact of life in today’s litigious society that a patient who contracts
bacterial endocarditis following dental treatment, or his or her estate, will file a malpractice suit against the dentist
who fails to ensure that the patient was premedicated with prophylactic antibiotics.”
The systemic connection as well as the legal connection of the oral cavity to the heart is very clear in the opinion of
Ms. Logan. The American Dental Association has always argued, “Following the Council on Dental Therapeutics
guidelines in your dental treatment will be the best deterrent to and defense against lawsuits.”
One veterinary investigator reported that large male dogs such as German Shepherd dogs would seem to be
particularly susceptible to bacterial endocarditis.23 The kidneys and spleen were reported to be the more common
sites of secondary infections. Typical clinical signs including fever leukocytosis, heart murmur, and lameness
occurred in only 18% of dogs in this series of 61 dogs. Only 44% of the dogs had the combination of fever,
leukocytosis and heart murmur. DeBowes, et al. compared periodontal disease and histologic lesions in 51 dogs; the
kidney was clearly the most common organ for related changes.17A case report of a dental extraction as the
probable cause of septicemia in a 10-year-old Pomeranian that ended with the dog’s death is a reminder that dental
procedures in dogs can have systemic effects.24
Oral microorganisms were cleared following experimental bacteremias in dogs usually within 10 minutes and
always within 20 minutes.25 The rate of clearance from the blood was neither dependent on the bacterial species nor
its source. These clearance times are comparable to those found in human studies, indicating surgical procedures or
instrumentation involving mucosal surfaces or contaminated tissue commonly cause transient bacteremia that rarely
persists more than 15 minutes in the bloodstream.”14 Nonetheless this 15 to 20 minute interval can be adequate to
transmit pathogens to conducive sites.
Membrane Penetration Effects of Oral Microbes
Hamlin 26 states in the conclusion of his studies designed to identify the cardiovascular and pulmonary diseases
affecting old dogs that:
“Geriatric dogs have a high prevalence of the following diseases:
Mitral regurgitation
Myocardial fibrosis
Dilated cardiomyopathy
Sick sinus syndrome
Tracheal collapse and
Bronchitis/pulmonary fibrosis/emphysema.
“The exact etiologies are unknown, but factors that might be involved include:
Chronic infection resulting from periodontal disease
Injury from proteinase
Myeloperoxidase produced by WBCs and macrophages
Environmental pollutants (including radioactivity)
Autoimmune factors and
Genetic predisposition.”
Loesche 14 posed the question, “Could it be that plaque flora does more than just challenge the gingival
epithelium?”
Teeth, as the only non-renewable surface in the body, harbor 10 8 colony forming units per mg of plaque with
initmate gingival epithelium contact. Periodontal patients have elevated serum fibrinogen and white blood cell
levels, which are strong predictors of coronary heart disease, thus linking dental disease and myocardial
infarction.27
The isolation of Chlamydia pneumoniae in coronary arterial fatty streaks and atheromatous plaques suggests that
chronic periodontal infections could have a role in cardiovascular disease.28 Although the mucous membrane can be
an effective barrier to bacteria, sterility of blood has rarely been challenged. Improved microbiological techniques
demonstrate the presence of two to 10 colony forming units/5 ml of indigenous bacteria from the skin, intestine, and
oral cavity, which are constantly gaining access to the internal body.14
Gingival crevicular fluid (GCV) is able to flush soluble noxious waste products and most nonadherent particular
matter. GCV contains large numbers of polymorphonuclear neutrophils (PMNs) that phagocytize bacteria.
Antibodies to plaque microbial species, complement, and antibacterial molecules such as a2macroglobulin assist
PMNs in their antibacterial activities. In addition, the rapid turnover of the gingival epithelial cells helps slough
away bacterial loads.
These defenses protect the host from frank microbial invasion, but an inflammatory response still occurs. This
inflammation can cause tissue loss when tissues are challenged by bacterial penetration or by a reactive bacterial
component such as lipopolysaccharide that reacts with the immune system.29 The immunological response to
subgingival plaque bacteria can be marked. The importance of plaque antigens in stimulating the immune system is
shown by high serum antibody titers to Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans,
which can be reduced by simple plaque removal. Major immune reactions occur to minor constituents of canine
subgingival flora, e.g., aerobic, non-fermenting Gram-negative bacilli.30 These constituents may influence the
progression and severity of gingival and periodontal lesions.31
Streptococcus sanguis is the primary supragingival plaque microorganism present when poor oral hygiene exists. If
S. sanguis enters periodontally inflamed tissue, it could penetrate the electrical membrane barrier and cause a low
level bacteremia because of its facultative nature. Platelet aggregation could occur predisposing the endothelial
lining of the cardiovascular system to fibrin and platelet deposits.
The parallel characteristics of Hamlin’s hypothesis for older dogs and Loesche’s for people provide an interesting
reinforcement to their common conclusion.
Pulmonary disease
Whenever oral clearance and swallowing is compromised due to stroke or decreased salivary levels oral periodontal
pathogens can be transported to the lungs and are implicated in death.32 Loesche33 compared the salivary levels of
24 individuals with aspiration pneumonia, 25 individuals with other pneumonia, and 60 matched individuals from a
Veterans Administration population. Although periodontal-associated species P. gingivalis, P. intermedia, P.
melaninogenicus, and Selenomonas sp. were similar in the three groups, Fusobacterium nucleatum and
Capnocytophaga sp. were found at a median 5.0 and 5.2 log10, respectively, in the saliva of individuals with
aspiration pneumonia compared to zero in other groups, p<0.05 and 0.01. This clinical result has been observed
numerous times in sanitariums and similar institutions where aspiration pneumonia occurs frequently.
In another age range, a 25-year-old male presented with an apparent routine, localized dental infection that
developed into life threatening abscess, starting in the right submandibular space.34 The infection rapidly spread
bilaterally into the neck, both lungs, and mediastinal space. After 56 days in the hospital, the patient self-discharged
when he was afebrile, normontensive, ambulatory, and alimenting normally.
This case report and Loesche’s study reinforce the predictions of Hamlin26 who associated oral with cardiovascular
and pulmonary diseases in old dogs, but also stressed that younger animals that presumably are most physically fit
can be the victim in a comparable situation. This common situation occurs in human beings and other animals, but
many of the specifics may be different.
The systemic complications of a set of dental patients in Japan presents some insight into the array of oral and
systemic interactions that can be present in a dental setting.35
Cardiovascular disease - 67.6%
Central nervous system disease - 2.3%
Endocrine disease - 1.1%
Hyperventilation syndrome - 6.9%
Allergy - 12.6%
Renal disease - 0.0%
Respiratory disease - 1.1%
Anaphylaxis - 0.0%
Others - 8.3%
Pulmonary diseases will vary in human populations as cited above and in companion animals in various veterinary
clinical situations. Nonetheless, the commonality of diseases is substantial.
Again, Hamlin stressed that pulmonary disease is not a frequent canine diagnosis, but cough is a common reason for
pet owners to bring animals to veterinarians. Similarly, people go to the dentist more frequently than to the
physician, so it’s the opportunity and responsibility of the dentist to be sensitive to systemic disease especially as it
is represented in the mouth.
Immune System
The oral soft tissues often provide the first diagnostic opportunity for human immunodeficiency virus (HIV)
infection. Acquired immunodeficiency syndrome (AIDS) presumably due to an impaired immune system, provides
increased opportunity for opportunistic infections.36 Mucosal Kaposi’s sarcoma, candidiasis, recurrent herpes
infection, hairy leukoplakia, and papilloma virus infection are examples of oral lesions associated with HIV
infection. HIV-infected patients, children and adults, are at increased risk for severe and aggressive periodontal
disease.37 They may have an atypical form of gingivitis (HIV-associated gingivitis and now called linear gingival
erythema) and a rapidly progressive, severe periodontitis (HIV-associated periodontitis and now called necrotizing
ulcerative periodontitis). The microbiological profile is similar to that of adult periodontitis suggesting that the
different clinical response reflects the compromised immune system of the host.
Little data are available to indicate whether feline immunodeficiency virus (FIV) has comparable oral ramifications,
although generalized stomatitis is a common clinical sign.38 One would expect the immune system of dogs and cats
to decline with disease and aging, based on experience with people.39-40
Acute necrotizing ulcerative gingivitis (ANUG) described as a rapidly destructive, noncommunicable, gingival
infection of complex etiology has been known by a variety of names including Vincent’s infection, acute
ulceromembranous gingivitis, ulcerative stomatitis, phagedenic gingivitis, and fusospirillary periodontal
gingivitis.41 Contributing factors include: systemic disease, e.g., cancer, altered host immune response; altered
immune systems, e.g., high serum IgA or IgM levels to spirochetes and P. intermedia, depressed chemotaxis, and
phagocytosis; and emotional stress.
Genetics
It is generally accepted that differences in periodontal disease among individuals cannot be attributed solely to the
qualitative and quantitative differences in the subgingival oral microflora.42 Susceptibility to periodontal disease
can be influenced by a number of genes that regulate humoral and cellular immune responses, development of the
oral hard and soft supporting tissues and the morphological development of teeth. Strongest support for genetic
influence is with the early onset of diseases such as juvenile periodontitis (JP). Generalized JP is consistently
associated with inherited or single gene disorders, such as Papillon-Lefevre syndrome43 and leukocyte adhesion
deficiencies. Papillon-Lefevre syndrome is characterized by diffuse and uniform palmoplanter hyperkeratosis as
well as destruction of the primary and secondary dentition, thus relating the skin and oral mucosal tissues.
Crohn’s disease1 is considered a distinct member of the inflammatory bowel disease family; however, its lesions
may occur anywhere along the mucosal tissue tract from the oral cavity to the anus. Initial clinical manifestation of
the disease may occur in the oral tissues, thus once again reaffirming the importance of oral diagnosis and the
relationships of oral and systemic interactions.
Hormonal Influences
Both progesterone and estrogen influences affect the physiology of host-parasite interactions in the oral cavity.44
Increased sex hormone levels correlate with an increased prevalence of gingivitis that is followed by remission as
levels decrease. Boys consistently have more gingival bleeding on probing than girls of comparable age, suggesting
that the level of oral hygiene may be more important in this age population than hormonal effects.45 Pregnancy
granuloma, also known as pregnancy tumor and epulis gravidarum, is similar in appearance to the gingival
hyperplasia that occurs with phenytoin therapy for epilepsy.46
Diabetes
The roles of diabetes and periodontal disease are debated.19,47 Periodontal disease is more prevalent and severe
among diabetics, but the variable nature of diabetes including type, duration, and level of control affects the
result.48 About 80 to 90% of people with diabetes mellitus are identified as insulin-dependent, or Type I diabetics
(characterized by pancreatic islet cell destruction). Type II diabetics have impaired insulin secretion, thus diabetic
control can often be achieved by a combination of therapies.
Diabetic patients are susceptible to a variety of chronic and acute complications including: neuropathy, nephropathy,
retinopathy, complications in pregnancy, and ketoacidosis. Microvascular changes such as thickening of the
basement membrane, periendothelial deposits, and narrowing of the lumen are similar in the oral cavity and other
organs and tissues of diabetic patients. These changes may affect nutrition and healing because of the impaired
delivery of nutrients to tissues, decreased oxygen diffusion, and impaired metabolic waste removal. This situation
may result in impaired leukocyte migration and reduced diffusion of immune mediators. The oral flora of diabetics
is generally comparable to that of nondiabetics, but differences occur reflecting the vascular changes associated with
the disease.
Discussion and Conclusions
Priorities
No one will disagree that the head is connected to the body, so activities in the head could be important to the rest of
the body. One can, however, debate:
What is causal
What is a risk factor
What is statistically significant and
What is clinically significant.
One, however, would think twice before debating with the chief counsel of the American Dental Association who is
trying to help member dentists when she says you, a member of the American Dental Association, should
premedicate a patient with a cardiac condition before doing routine dentistry including a dental prophylaxis.22 This
is a clear re-affirmation that the oral cavity and its treatment is indeed important to the heart especially when the
health of the heart is compromised by past or present disease.
One can conclude similarly, when major medical centers put in their protocol guidelines: to treat dental disease
before treating cardiac disease.16,49 This situation is occurring more often as medical centers and hospital staff
recognize the importance of oral disease as a complicating factor in the success of major systemic surgical treatment
procedures.
This recommendation is in contrast to the all too often veterinary decision to delay needed dental procedures until
other procedures requiring anesthesia are indicated. Anesthesia protocols for companion animals of all ages and
types are available, so this concern should not preclude doing dentistry first.50
It is important to recognize that bacteremia will not occur with every dental prophylaxis but the animal host needs to
be treated in totality and treating earlier is better than later and considerably better than not treating.
Prevention
By definition, prevention is observing and treating early, regularly, and as often as needed. Ultimately, biological
systems will weaken, break down and life’s conclusion will occur. Meanwhile preventive measures will slow the
onset of disease and increase the probability of a less stressful good quality of life for the animal, its owner and the
participating veterinary group.
First steps
Clean the mouth regularly and often. Improve oral cleansing and turnover to minimize challenges and maximize
natural defense mechanisms. Regular oral cleansing with optimal nutrition has been possible with a new
maintenance food.51,53 This maintenance food minimizes the challenge to oral tissues while maximizing oral
cleansing to control plaque and gingivitis as well as stain and calculus.
Plaque can be removed effectively by regular toothbrushing in companion animals and people. Plaque accumulation
is highly correlated with gingivitis.54 Although gingivitis does not always advance to periodontal disease,
periodontal disease is always preceded by gingivitis. Thus it is prudent to control plaque accumulation and gingivitis
as a first step to controlling periodontal disease. Controlling periodontal disease will minimize the concern for oral
disease and its components that contribute to systemic disease.
The mouth is the major and primary portal of entry. Pederson suggested that the best place to stop disease is the
portal of entry, the mouth.38 This is a prudent first step.
References
1.Kalamar JR. Crohn’s Disease: Orofacial Considerations and Disease Pathologies. Periodontol 2000 1994;6:101-115.
2.Navia JM. Animal Models in Dental Research.
Birmingham:University of Alabama Press 1984.
3.Saxe SR, et al. Oral Debris, Calculus and Periodontal Disease in the Beagle Dog. Periodontics 1967;5(5):217-225.
4.Lindhe J, Hamp SE, Loe H. Experimental Periodontitis in the Beagle Dog. J Periodont Res 1973;8(1):10.
5.Fox JG. Biology and Diseases of the Ferret. Philadelphia:Lea & Febiger 1988;256.
6.Boden E. Sheep and Goat Practice. London:Bailliere Tindall 1991;133-155.
7.World Health Organization. the Economics of Health and Disease. WHO Chronicle 1971;25:20-24.
8.Hollister MC, Weintraub JA. The Association of Oral Status with Systemic Health, Quality of Life and Economic Productivity. J Dent Ed
1993;57(12):901-912.
9.Farrell JH. the Effect of Mastication on the Digestion of Food. Brit Dent J 1956;101(5):149-156.
10.Rhodus NL, Brown JB. The Association of Xerostomia and Inadequate Intake in Older Adults. J Amer Diet Assoc 1990;90(12):1688-1692.
11.Dolan TA, et al. Geriatric Grand Rounds: Oral Diseases in Older Adults. J Amer Ger Soc 1990;38(1):1239-1250.
12.Loesche WJ, Bromberg J, Terpenning MS, et al. Xerostomic Medications and Food Avoidances in Selected Geriatric Groups. J Amer Ger
Soc 1995;43(4):401-407.
13.Alvares O. Nutrition, Host Defense and Periodontal Disease: Laboratory and Animal Studies. In: Foods, Nutrition and Dental Health,
Hefferren JJ, Koehler HM, Osborn JC eds. Chicago:American Dental Association Health Foundation 1984;149-161.
14.Loesche WJ. Periodontal Disease as a Risk Factor for Heart Disease. Compen Contin Ed Dent 1994;15(8):976-991.
15.SyrjŠnen J, Peltola J,Valtonen V, et al. Dental Infections in Association with Cerebral Infarctions in Young and Middle-aged Men. J Intern
Med 1989;225:179-184
16.Mattila KJ, Nieminen MS, Valtonen VV, et al. Association Between Dental Health and Acute Myocardial Infarction. Brit Med J
1989;298:779-782.
17.DeBowes LJ, Mosier D, Logan E, et al. A Comparison of Periodontal Disease and Histological Lesions in Multiple Organs from 51 dogs.
Submitted for publication.
18.DeStefano F, Anda RF, Kahn, et al. Dental Disease and Risk of Coronary Heart Disease and Mortality. Brit Med J 1993;306:688-691.
19.Genco RJ, Loe H. The Role of Systemic Conditions and Disorders in Periodontal Disease. Periodontol 2000 1993;2:98-116.
20.Sandler HC, Stahl SS. Prevalence of Periodontal Disease in a Hospitalized Population. J Dent Res 1960;39:439-449.
21.Sandler HC, Stahl SS. The Influence of Generalized Diseases on Clinical Manifestations of Periodontal Disease. J Amer Dent Assn
1954;49:656-667
22.Council on Dental Therapeutics: American Heart Association. Preventing Bacterial Endocarditis: A Statement for the Dental Professional.
J Amer Dent Assn 1991;122(2):87-92.
23.Calvert CA. Valvular Bacterial Endocarditis in the Dog. JAVMA 1982;180(9):1080-1084.
24.Withrow SJ. Dental Extraction as Probable Cause of Septicemia in a Dog. JAAHA 1979;15:345-346.
25.Silver JG, Martin L, McBride BC. Recovery and Clearance Rates of Oral Microorganisms Following Experimental Bacteremias in Dogs.
Arch Oral Biol 1975;20:670-675.
26.Hamlin RL. Identifying the Cardiovascular and Pulmonary Diseases that Affect Old Dogs. Vet Med 1990;483-497.
27.Kweider M, Lowe GDO, Murray GD, et al. Dental Disease, Fibrinogen and White Blood Cell Counts; Link Myocardial Infarction? Scot Med
J 1993;38:73-74.
28.Kuo CC, Shor A, Campbell LA, et al. Demonstration of Chlamydia pneumoniae in Atherosclerotic Lesions of Coronary Arteries. J Infect
Dis 1993;167:841-849.
29.Schenck K, Kelgeland K, Tollefesen T. Antibodies Against Lipopolysaccharide from Bacteroides gingivalis before and after Periodontal
Treatment. Scand J Dent Res 1987;95:112-118.
30.Boyce E, Logan E, Hunt J, et al. Gram-negative Bacilli and Unusual Bacilli in Canine Subgingival Plaque. J Dent Res 1994;73:345.
31.Gaeddert K, Logan E, Brown C, et al. Immune Reactivity to Subgingival Microbial Isolates in Dogs. J Dent Res 1994;73:430.
32.Bartlett JG. Anaerobic Bacterial Pneumonitis. Amer Rev Respir Dis 1979;119:19-23.
33.Loesche WJ, Terpenning MS, Bromberg J, et al. A Possible Role for Salivary Bacteria in Aspiration Pneumonia. J Dent Res 1995;74:127.
34.Petrone JA. Mediastinal Abscess and Pneumonia of Dental Origin. J NJ Dent Assoc 1992;63(4):19-23.
35.Matsuura H. Systemic Complications and their Management During Dental Treatment. Intl Dent J 1989;39:113-122.
36.Murray PA.Periodontal Diseases in Patients Infected by Human Immunodeficiency Virus.Periodontol 2000 1994;6:50-67.
37.Murray PA. HIV Disease as a Rick Factor for Periodontal Disease. Compend Contin Ed Dent 1994;15(8):1052-1063.
38.Pedersen NC. Inflammatory Oral Cavity Diseases of the Cat. Vet Clin N Amer Sm Anim Pract 1992;22(6):1323-1345.
39.Hall JA. Aging and Immune System. Proc Symp Health and Nutr Geriatric Cats and Dogs. Jan 12, 1996:25-29.Orlando, FL.
40.Hefferren JJ, Boyce E, Bresnahan J. Aging and Oral Health. Proc Symp Health and Nutr Geriatric Cats and Dogs. Jan 12, 1996:21-24.
Orlando, FL.
41.Murayama Y, Kurihara H, Nagai A, Dompkowski D, Van Dyke TE. Acute Necrotizing Ulcertative Gingivitis: Risk Factors Involving Host
Defense Mechanism. Periodontol 2000 1994;6:116-124.
42.Michalowicz BS. Genetic Risk Factors for Periodontal Disease. Compen Contin Ed Dent 1994;15(8):1036-1050.
43.Hart TC, Shapiro L. Papillon-Lefevre Syndrome. Periodontol 2000 1994;6:88-100.
44.Amar S, Chung KM. Influence of Hormonal Variation on the Periodontium in Women. Periodontol 2000 1994;6:79-87.
45.Addy M, Dummer PMH, Hunter ML, Kingdon A, Shaw WC. The Effect of Toothbrushing Hand, Sex and Social Class on the Incidence of
Plaque, Gingivitis and Pocketing in Adolescents: A Longitudinal Cohort Study. Community Dent Health 1989;7:237-247.
46.Hassell TM, Burtner AP, McNeal D, Smith RG. Oral Problems and Genetic Aspects of Individuals with Epilepsy. Periodontal 2000
1994;6:68-78.
47.Yalda B, Offenbacher S, Collins JG. Diabetes as a Modifier of Periodontal Disease Expression. Periodontol 2000 1994;6:37-49.
48.Shlossman M. Diabetes and Periodontal Disease - A Current Perspective. Compend Contin Ed Dent 1994;15(8):1018-1031.
49.Hughes RK. A Method of Improved Antisepsis for Open-Heart Surgery. Ann Thor Surg 1966;2(2):230-236.
50.Hartsfield SM. Anesthetic Problems of the Geriatric Dental Patient. Prob Vet Med 1990;2(1):24-43.
51.Simone A, Logan EI, Richardson D, et al. Dietary Control of Canine Plaque and Calculus. J Dent Res 1995;74:80.
52.Logan EI, Maseman D. Irvine G, et al. Canine Gingivitis and Diet. J Dent Res 1995; 74:79.
53.Logan EI, Finney O, Irvin G, Hefferren J. Dietary Control of Plaque and Gingivitis, J Dent Res 1996;75:190.
54.Loe H. Periodontal Diseases: A Brief Historical Perspective. Periodontol 2000 1993;2:7-12.