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It should be noted that exposure resulting from medical procedures and background radiations are not included in occupational dose limits buy tamoxifen 20mg line pregnancy leg cramps. These devices should be taken off during any medical procedures involv- ing radiation such as radiographic procedures and dental examinations cheap tamoxifen 20mg amex menstruation synchronization, and also when leaving after the day’s work buy cheap tamoxifen 20mg on line pregnancy test calculator. Also radiation workers should not wear these badges for certain period of time after undergoing a diagnostic or therapeutic nuclear medicine procedure or radiation therapy permanent implant procedure. Dos and Don’ts in Radiation Protection Practice Do wear laboratory coats and gloves when working with radioactive materials. For iodine radionuclides, bioassay is performed by the thyroid uptake test within 72hr and at 14 days after handling the radioactivity. Radiation Regulations and Protection required for other radionuclides, depending on the amount and type of radionuclides. The suppliers require documentation of licensing of the user as to the types and limits of quantities of radioactive material before shipping. Monitoring of packages is required if the packages are labeled as con- taining radioactive material to check if the packages are damaged or leaking. A radioactive shipment must be monitored as soon as possible after receipt but no later than 3hr after delivery if the delivery takes place during normal hours, or not later than 3hr from the beginning of the next working day if it is received after working hours. Two types of monitoring are per- formed: survey for external exposure and wipe test for contamination on the surface of the package resulting from potential leakage of liquid. The survey reading of external exposure should not exceed 200mrem/hr (2mSv/hr) on the surface of the container or 10mrem/hr (100mSv/hr) at 1m from the surface of the container. The wipe test is performed by swab- bing an area of 300cm2 of the package and should show less than the limit 2 of 6600dpm or 111Bq/300cm. Advice should be sought from these authorities as to whether the shipment should be returned. The information logged in includes the date of the receipt, the man- ufacturer, the lot number, name and quantity of the product, date and time of calibration, and survey data along with the name of the individual pro- cessing the receipt. Radioactive Waste Disposal Radioactive waste generated in nuclear medicine or pharmacy (e. Radionuclides with half-lives less than 120 days usually are disposed of by this method. These radionuclides are allowed to decay in storage and monitored before disposal. If the radioactivity of the waste cannot be distinguished from back- ground, it can be disposed of in the normal trash after removal or defacing of all radiation labels. This method is most appropriate for 99m 123 201 111 67 131 shortlived radionuclides such as Tc, I, Tl, In, Ga and I. Radioac- tivities should be stored separately according to half-lives for convenience of timely disposal of each radionuclide. Excreta from humans undergoing medical diagnosis or treatment with radioactive material are exempted from these limitations. To adopt this method of radioactive disposal, one must determine the total volume and the ﬂow of sewer water in the institution and the number of users of a speciﬁc radionu- clide so that for each individual user, a limit can be set for sewer disposal of the radionuclide in question. Transfer to Authorized Recipient This method of transfer to an authorized recipient is adopted for longlived radionuclides and usually involves transfer of radioactive wastes to autho- rized commercial ﬁrms that bury or incinerate at approved sites or facilities. Although the columns of the 99Mo–99mTc generators may be decayed to background for disposal to normal trash, a convenient method of disposing of this generator is to return them to the vendors, who let them decay and later dispose of them. Normally, the used generator is picked up by the authorized carrier when a new one is delivered. Radiation Regulations and Protection Other Disposal Methods A licensee may adopt methods of radioactive waste disposal different from those mentioned here, provided regulatory agency approval is obtained. Impact of such disposal methods on environment, nearby facilities, and population is heavily weighed before approval. Incineration of solid radio- active waste and carcasses of research animals containing radioactive 133 materials is allowed by this method. Records must be maintained as to the date of storage and the amount and kind of activity stored in a waste disposal log book. The date of disposal and the amount of disposed activity must also be recorded in the log book, along with the initials of the individual disposing of the waste. Radioactive Spill Accidental spillage of radioactivity can cause unnecessary radiation exposure to personnel and must be treated cautiously and expeditiously. A major spill usually occurs when the spilled activity cannot be contained in a normal way and can cause undue exposure to personnel. Areas, personnel, and equipment must be decontami- nated, keeping in mind the principle of containment of radioactivity. Recordkeeping Records must be maintained for the receipt, storage, and disposal of radioactive materials, as well as for various activities performed in the radi- ation laboratories. The 99m 99 99m Tc activity is eluted from the Mo- Tc generator and reagent kits are 99m used to prepare Tc-labeled radiopharmaceuticals according to instruc- tions given by the manufacturer in the package inserts. Applications, Amendments, and Notiﬁcations As already mentioned, applications for a license and its renewals must be made by the licensee’s management for the medical uses of by-product materials. Amendments to the license must be made by the licensee’s man- agement for the following: (a) Appointment or discontinuation of an authorized user, radiation safety ofﬁcer, authorized medical physicist, or authorized nuclear pharmacist (b) Change of name or address of the licensee (c) Change or addition of the use areas (d) Use of excess or new by-product materials not permitted before in the license 284 16. Radiation Regulations and Protection Notiﬁcation of the above must be made within 30 days of occurrence. Licenses with Type A speciﬁc license of broad scope are exempt from these requirements. There is no requirement for periodic review of the supervised individual’s work and records. The licensee is responsible for the acts and omissions of the supervised individuals. The written directive must be dated and signed by an authorized user and must contain the patient’s name, the dosage, the name of the drug, and route of administration. A revision of the written directive can be made, if necessary, provided it is signed and dated by the authorized user before administration. In case of an emergency, an oral revision to an existing written directive is acceptable, which must be followed by a written directive within 48 hours. The identity of the patient may be veriﬁed by the name, driver’s license, birthday, any hospital’s I. For unit dosages, the activity can be determined by direct measurement or by the decay correction of the activity provided by the licensed manu- facturer. Radiation Regulations and Protection mined by direct measurement, a combination of measurement of radioac- tivity and mathematical calculations, or a combination of volumetric mea- surements and mathematical calculations based on the activity provided by the manufacturer. Unless otherwise directed by the authorized user, the licensee may not use a dosage if it does not fall within the prescribed dosage range, or if it differs from the prescribed dosage by more than 20%.
Omics proﬁling should serve as the basis for research in aerospace per- sonalized medicine and explore methodological considerations to advance the ﬁeld order tamoxifen master card women's health letter. Personalized medicine may become the standard of care for humans in space in the future cheap 20 mg tamoxifen mastercard pregnancy freebies. Pharmacogenomics and serotonergic agents: research observations and potential clinical practice implications buy tamoxifen now menstrual urban dictionary. Diabetes as a case study of chronic disease management with a personalized approach: the role of a structured feedback loop. Stratiﬁed medicine for the use of anti-diabetic medication in treatment of type 2 diabetes and cancer: where do we go from here? Conﬁrmation of the association between male pattern baldness and the androgen receptor gene. Toward a personalized medicine approach to the manage- ment of inﬂammatory bowel disease. Personalized medicine in human space ﬂight: using omics based analy- ses to develop individualized countermeasures that enhance astronaut safety and performance. Patient perspectives on personalized glucose advisory systems for type 1 diabetes management. Therapeutic drug monitoring in inﬂammatory bowel disease: current state and future perspectives. Universal Free E-Book Store Chapter 19 Personalized Non-pharmacological Therapies Introduction Most of the discussion in personalized medicine relates to pharmacological therapies. Some non-pharmacological approaches that have become a part of integrated modern healthcare are also personalized and will be discussed here brieﬂy. Acupuncture Acupuncture, as the derivation of the word implies (acus meaning needle; puncta meaning puncture), is the insertion of a needle into the skin of the human body. The ancient Chinese attributed disease to an imbalance between Yin (negative) and Yang (positive) forces. Acupuncture was used mostly for the relief of pain and muscular dis- ability but has been applied to other disorders as well. The mechanism of action is not well understood and is the topic of most of the research studies. Acupuncture is the most commonly integrated of the alternative methods into conventional medical practice. It does not conﬂict with modern neuromuscular anatomy and pain physiology even though it is based on the classical Chinese con- cept of a subtle circulation network of a vivifying force called Qi. This hybrid acu- puncture approach expresses the best of both worlds by describing a context in which to organize patient symptoms that usually escape attention in the standard medical evaluation. Acupuncture is performed at certain speciﬁed points (acupuncture points) that are located on the 12 major meridians on the body, each corresponding to a major organ system of the body. The selection of acupuncture points is personalized according to each patient, location of pain and other symptoms. Personalized Acupuncture Therapy Acupuncture needs to be tailored to each patient’s particular symptoms as well as responsiveness and it is generally recognized that individualization of acupuncture treatment enhances its effectiveness. Apart from variable selection of acupuncture points, the dose should be determined for each patient. The dose depends not only on the intensity of stimulation but may be affected by the state of the patient, e. A randomized controlled trial has compared the effectiveness of standardized and individualized acupuncture treatment in patients with chronic low back pain (Pach et al. Patients received either standardized acupuncture or individual- ized acupuncture. Treatment consisted of 10–15 treatments based on individual symptoms with two treatments per week. The authors suggested that a multicenter noninferiority study should be performed to investigate whether standardized acupuncture treatment for chronic low back pain might be applicable in a broader usual care setting. It is extremely sensitive in the early detection of a cerebrovascular disturbance and can delineate the natural course of an episode that can lead to cerebral infarction. The effect of a therapeutic intervention can be assessed by demonstrating the complete or partial reversal of these physiological and bio- chemical parameters. Any nuclear medicine facility with a gamma camera has the capability for this procedure. This scan documents the area of cerebral infarction as diminished uptake, and any improvement is easy to document by noting the increased uptake of the tracer. Personalized Nutrition Nutrition plays a crucial role in health as well as disease. Nutraceuticals are dietary supplements such as vitamins, minerals and antioxidants, which can be used for prevention and treatment of diseases. With advances in molecular biology, there is a shift in focus from epidemiology and biochemistry to an understanding of how nutrients act at molecular level. Advances in genomics have led to recognition of the importance of genes in human nutrition. Genetic predisposition is an important fac- tor in mortality linked to diet such as cardiovascular disease. Whereas traditional nutrition research has dealt with providing nutrients to nourish populations, it nowa- days focuses on improving health of individuals through diet. Modern nutritional research is aiming at health promotion and disease prevention and on performance improvement. Universal Free E-Book Store 580 19 Personalized Non-pharmacological Therapies Technologies such as high-density microarrays enable the simultaneous study of the whole transcriptome relevant to nutrition. Advances in proteomic and metabo- lomic technologies will also enable the analysis of the whole system at proteomic and metabolomic levels as well. Nutrigenomics The term “nutrigenomics” or nutritional genomics implies the study of effects of nutrition at the genome level. This approach analyzes how a complex trait is pro- duced by the interaction of a person’s genes and the environments including nutri- tion. A closely related term “nutrigenetics” examines the effect of genetic variation on the interaction between nutrition and disease. Individual genetic variation can inﬂuence how nutrients are assimilated, metabolized, stored, and excreted by the body. A major methodological challenge and ﬁrst prerequisite of nutrigenomics is inte- grating genomics, transcriptomics, proteomics and metabonomics to deﬁne a “healthy” phenotype. It is important to recognize that an individual’s response to dietary intervention will depend on his or her genetic back- ground and that this information may be used to promote human health and disease prevention (Trujillo et al. The long-term deliverable of nutrigenomics is per- sonalized nutrition for maintenance of individual health and prevention of disease. Nestle Research Center (Lausanne, Switzerland), a part of the world’s largest nutrition company, is conducting research in nutrigenomics. There is a Center of Excellence for Nutritional Genomics at University of California at Davis. Research and postgraduate training in nutrigenomics is being conducted at the Center for Human NutriGenomics in the Netherlands (http://www. For nutrigenomics to realize its potential, large ethnically diverse databases of genomic proﬁles need to be established.
Ethnic factors discount 20mg tamoxifen visa women's health liposlim, therefore purchase 20mg tamoxifen minstrel knight tyrant, are an important consideration in individualization of therapy order tamoxifen 20 mg line houston women's health care center. Gender Differences in Pharmacogenetics There are gender-related differences in pharmacokinetics, which may be related to pharmacogenetic differences in to drug-metabolizing enzymes. Other gender differences in pharmacokinetics may be due to ﬂuctuations in hormone levels in women with menstruation and pregnancy. Moreover, development of diseases such as heart disease and cancer may affect women differently from men. There is no data to support the efﬁcacy of statins in preventing heart attacks and stroke in women with hypercholesterolemia, partly because there have not been adequate representation of women in clinical Universal Free E-Book Store Role of Pharmacogenetics in Pharmaceutical Industry 115 trials as compared to men. Use of statins in women is associated with a higher rate of complications such as myositis and cognitive impairment. Statin therapy in women without cardiovascular disease is controversial, given the insufﬁcient evidence of beneﬁt. Participants included 6,800 women and 11, 000 men with high- sensitivity C-reactive protein and low-density lipoprotein cholesterol randomized to rosuvastatin versus placebo. Meta-analysis studies were randomized placebo- controlled statin trials with predominantly or exclusively primary prevention in women and sex-speciﬁc outcomes. This study demonstrated that in primary preven- tion rosuvastatin reduced cardiovascular disease events in women with a relative risk reduction similar to that in men, a ﬁnding supported by meta-analysis of pri- mary prevention statin trials. Role of Pharmacogenetics in Drug Safety Variability in drug response among patients is multifactorial, including environmen- tal, genetic, and disease determinants that affect the disposition of the drug. Children may be exposed to these drugs through in utero exposure during preg- nancy, through breast feeding, and through exposure during adolescence. Adverse Drug Reactions Related to Toxicity of Chemotherapy Neurotoxicity and myelotoxicity are well known adverse reactions of chemother- apy in cancer patients. Additionally, patients who were homozygous variant at the 2677 and 3435 loci had a signiﬁcantly greater percent decrease in absolute neutrophil count at nadir. Polymorphisms in the genes that code for drug-metabolizing enzymes, drug transporters, drug receptors, and ion channels can affect an individual’s risk of having an adverse drug reaction, or can alter the efﬁ- cacy of drug treatment in that individual. Mutant alleles at a single gene locus are the best studied individual risk factors for adverse drug reactions, and include many genes coding for drug-metabolizing enzymes. These genetic polymorphisms of drug metabolism produce the phenotypes of “poor metabolizers” or “ultrarapid metabolizers” of numerous drugs. The vast majority arise from classical polymorphism in which the abnormal gene has a prevalence of more than 1 % in the general population. Toxicity is likely to be related to blood drug concentration and, by implication, to target organ concentration as a result of impaired metabolism. The other type is rare and only 1 in 10,000 to 1 in 100,000 persons may be affected. Mutant alleles at a single gene locus are the best studied individual risk factors for adverse drug reactions, including the genes for N-acetyltransferases, thiopurine methyltransferase, dihydropyrimidine dehydro- genase, and cytochrome P450. However, pharmacogenetic factors rarely act alone; rather they produce a phenotype in concert with other variant genes such as those for receptors and with environmental factors such as cigarette smoking. Most idiosyncratic drug reactions are unpredictable and because of their rarity my not show up in patients during clinical trials with a few thousand patients. They may ﬁrst surface when the drug has been taken by hundreds of thousands of patients in the post-marketing phase. Pharmacogenetics, by individualizing treatment to patients for whom it is safe, provides a rational framework to minimize the uncer- tainty in outcome of drug therapy and clinical trials and thereby should signiﬁcantly reduce the risk of drug toxicity. Topiramate, an anticonvulsant medication, is an efﬁcacious treatment for alcohol dependence. Future studies in larger samples are needed to more fully establish these preliminary ﬁndings. In other situations, it may help in the adjustment of dose of the drug such as in warfarin therapy. Clinical signs include unexplained elevation of end-tidal Universal Free E-Book Store Role of Pharmacogenetics in Pharmaceutical Industry 119 carbon dioxide, muscle rigidity, acidosis, tachycardia, tachypnea, hyperthermia, and evidence of rhabdomyolysis. However, it is invasive, requiring skeletal muscle biopsy and is not widely available. Researchers have begun to map mutations within the ryanodine receptor gene (chromosome 19q13. Pharmacogenetics of Clozapine-Induced Agranulocytosis Clozapine has long been accepted as one of the most effective medications for treat- ing schizophrenia but has had limited utilization due to the risk of inducing agranu- locytosis, a life-threatening decrease of white blood cells that requires frequent blood testing of patients. This raised the hope for a one-time genetic test may obviate the need for continuous blood monitoring for the majority of clozapine- treated patients. These ﬁndings have uncovered new clues to the underlying biological and physiologic mechanisms of drug-induced agranulocytosis and provide a starting point for eluci- dating a common mechanism across drugs from different classes that carry this rare but devastating side effect. The sensitivity and selectivity of these biomarkers could support further development of a diagnostic test. However, no genetic test is currently available for clozapine-induced agranulo- cytosis. Candidate gene studies have failed to identify a strong, replicated genetic variant that substan- tially increases risk of clozapine-induced agranulocytosis. Combined analysis of such studies may identify associated genetic variants that can be rapidly translated to clinical practice. Universal Free E-Book Store 120 4 Pharmacogenetics Role of Pharmacogenetics in Warfarin Therapy Warfarin (Coumadin) is the most commonly prescribed oral anticoagulant for the treatment and prevention of thromboembolic events. The correct mainte- nance dose of warfarin for a given patient is difﬁcult to predict, the drug carries a high risk of toxicity, and variability among patients means that the safe dose range differs widely between individuals. Recent pharmaco- genetic studies indicate that the routine incorporation of genetic testing into warfa- rin therapy protocols could substantially ease both the ﬁnancial and health risks currently associated with this treatment (Reynolds et al. The labeling update is a milestone that brings personalized medicine to the main- stream. To this end, there are numerous studies currently ongoing looking at outcomes when genetic tests are incorporated into warfarin treat- ment. The Harvard Partners Center for Genetics and Genomics, Medco and the Mayo Clinic, Clinical Data and PharmaCare, and the University of Utah under the Critical Path Initiative, are all researching the clinical utility of pharmacogenetics-based war- farin dosing. Mutations in three speciﬁc genes can increase an individual’s risk for dangerous blood clots and their leading complication, and is an indication for warfarin therapy. The use of a pharmacogenetic algorithm for estimating the appropriate initial dose of warfarin produces recommendations that are signiﬁcantly closer to the required sta- ble therapeutic dose than those derived from a clinical algorithm or a ﬁxed-dose approach (The International Warfarin Pharmacogenetics Consortium 2009). Universal Free E-Book Store Role of Pharmacogenetics in Pharmaceutical Industry 121 A genome-wide association study found gene polymorphisms that affect the anticoagulant effect of warfarin (Takeuchi et al. These results provide justiﬁcation for conducting large-scale trials assessing patient beneﬁt from genotype-based forecasting of warfarin dose. Role of Pharmacogenetics in Antiplatelet Therapy The antiplatelet agent clopidogrel (Plavix) is used in the management of cardiovas- cular disease and stroke, but genetic mutations may reduce the effect of this drug. Persons with these gene variants carry double or triple the risk of death, myocardial infarction or stroke, compared with people with the normal metabolism alleles.
It is now recognized that aggressive periodontitis can affect the primary and permanent dentitions both in localized and generalized forms generic 20 mg tamoxifen fast delivery menstruation and diarrhea. The tissues become hyperplastic with granular or nodular proliferations that precede gingival clefting and extensive areas of recession discount tamoxifen 20mg on line menopause queasy. Gross deposits of plaque are inevitable as the soft tissue changes make it difficult to maintain oral hygiene discount 20 mg tamoxifen mastercard womens health 6 week running program. The disease progresses extremely rapidly, with primary tooth loss occurring as early as 3-4 years of age. The entire dentition need not be affected, however, as the bone loss may be restricted to one arch. Children with generalized disease are susceptible to recurrent general infections, principally otitis media and upper respiratory tract infections. Localized disease progresses more slowly than the generalized form and bone loss characteristically affects only incisor-molar teeth. Plaque levels are usually low, consequently soft tissue changes are minimal with gingivitis and proliferation involving only the marginal tissues. The predominant micro-organisms that have been identified are aggressive periodontopathogens: Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Fusobacterium nucleatum, and Eikenella corrodens. Profound abnormalities in chemotaxis and phagocytosis of polymorphonuclear neutrophils and monocytes are frequently reported in these patients. These immunological defects are heritable risk factors that help to define phenotypically the disease entity. Conversely, they may also be associated with more serious and life-threatening conditions, and thus a full medical screen is indicated. Oral hygiene instruction, scaling, and root planing should be undertaken at frequent intervals. If pathogens persist after oral debridement, an antibiotic such as metronidazole or amoxycillin (amoxicillin) should be given systemically after sensitivity testing, as a short course over 1-2 weeks. Some improvement has been achieved following a granulocyte transfusion in a patient with a defect in neutrophil function. Extraction of involved teeth has also produced an improvement in neutrophil chemotaxis, which suggests that the defect may be induced by certain organisms in the periodontal flora. Furthermore, in severe cases of generalized periodontitis, extraction of all primary teeth (and the provision of a removable prosthesis) can limit the disease to the primary dentition. When the permanent teeth erupt, bacterial culturing of the subgingival flora ensures that reinfection is detected early. Key Points Primary dentition (prepubertal periodontitis): • localized/generalized; • aggressive pathogens; • intense treatment. The localized form occurs in otherwise healthy individuals, with destruction classically localized and around the first permanent molars and incisors, and not involving more than two other teeth. Generalized periodontitis also occurs in otherwise healthy individuals but involves more than 14 teeth, that is, being generalized to an arch or the entire dentition. Some reports have monitored children suffering from aggressive periodontitis of the primary dentition to find that, at around puberty, the disease became generalized to involve the entire dentition. In the United Kingdom an epidemiological study of 7266 schoolchildren in Coventry and Birmingham showed an overall prevalence of 0. There was no difference in prevalence between males and females, which does not concur with the data of many earlier epidemiological studies of the disease which reported a female to male ratio of 3 : 1. The clinical features are pocket formation and loss of attachment associated with the permanent incisors and first molar teeth. Bilateral angular bone defects are identified on the mesial and, or distal surfaces of molars (Fig. Angular defects are sometimes seen around the incisors, although the very thin interproximal bone is resorbed more evenly to give a horizontal pattern of resorption. The gingiva can appear healthy when the levels of plaque are low, but a marginal gingivitis will be present if a good standard of plaque control is not evident. The pattern may be a combination of angular and horizontal resorption producing an irregular alveolar crest. When patients have good plaque control the degree of bone resorption is not commensurate with the level of oral hygiene. The more generalized nature of the disease predisposes to multiple and recurrent abscess formation which is a common presenting feature. Invariably, one of the presenting signs is tooth migration or drifting of incisors. Conversely, extensive bone loss can occur with no spontaneous movement of teeth and the subject may only be alerted to the problem when a minor traumatic episode, such as a blow to the mouth during a sporting activity, causes unexpected loosening of teeth. Bacteriology and pathogenesis The subgingival microflora comprises loosely adherent, Gram-negative anaerobes including Eikenella corrodens, Capnocytophaga spp. The most frequently implicated organism is Actinobacillus actinomycetemcomitans, which has been found in over 90% of patients. Key Points Permanent dentition (Juvenile periodontitis): • onset around puberty; • localized/generalized; • Actinobacillus actinomycetemcomitans; • neutrophil chemotaxis defect. The chemotactic defect is linked to reduced amounts of cell-surface glycoproteins and is transmitted as a dominant trait. About 50% of siblings of patients who have both aggressive periodontitis and chemotactic defects, also demonstrate impaired neutrophil function. Treatment A combined regimen of regular scaling and root planing with a 2-week course of systemic tetracycline therapy (250 mg, four times daily) has been used extensively in the management of this condition. More recently, a combination of metronidazole (250 mg) and amoxicillin (amoxycillin) (375 mg), three times a day for 1 week, in association with subgingival scaling, has also been found to be effective. A more radical approach is to undertake flap surgery so that better access is achieved for root cleaning, and the superficial, infected connective tissues are excised. An antimicrobial regimen can also be implemented in conjunction with a surgical approach. Key Points Permanent dentition (juvenile periodontitis)⎯treatment: • plaque control; • mechanical debridement; • systemic antimicrobials; • periodontal surgery. The contour of the bone crest on the mesial of |7 gives the impression of a vertical bony defect. Furthermore, genetic factors are implicated in the pathogenesis of the diseases as many affected patients have functionally defective neutrophils. The apparent increased incidence in females suggests an X-linked dominant mode of inheritance with reduced penetrance. The association with females, however, may reflect epidemiological bias as females are more likely to seek dental attention. Large family studies of subjects with aggressive periodontitis suggest an autosomal-recessive pattern of inheritance. The role of hereditary components in periodontal diseases has been supported by the link with specific tissue markers.