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PubMed2004

An investigation of mammographic density and gene variants in healthy women.

This cross-sectional study examined if polymorphisms in genes that code for enzymes involved in the production and metabolism of estrogens are associated with mammographic density, a strong predictor of breast cancer risk. The study included 328 healthy women of different ethnicities who underwent mammographic screening and donated a blood or mouthwash sample for DNA analysis. After digitizing cranio-caudal views of the mammograms, we performed computer-assisted mammographic density assessment. Following DNA extraction, samples were analyzed for polymorphisms in the COMT (Val158Met), CYP1A1 (Ile462Val), CYP1B1 (Val432Leu), CYP1A2 (*1F) and CYP17 (T27C) genes using PCR-RFLP. Breast density was lower in Caucasians than in Asians. Caucasian women were less likely to carry the CYP1A1 variant allele and more likely to carry the variant alleles for CYP1B1 and COMT than women with Asian or Hawaiian ancestry. The low-activity COMT and CYP1A2 variant alleles were weakly related to lower percent mammographic density after adjustment for age, ethnicity, body mass index and reproductive variables (p for gene-dosage =0.08 and 0.05, respectively). These relations were observed in premenopausal women only and were similar in direction and magnitude after stratification by ethnicity. We found no significant associations between breast density and the variant alleles for CYP1A1, CYP1B1 and CYP17. Our data suggest lower mammographic density for women carrying the COMT and CYP1A2 variant alleles than for women carrying the common alleles, though this is the opposite of what is commonly hypothesized from the enzyme function.

Adult↗

PubMed2005

Identification of human papillomaviruses in tumors of the oral cavity in an Indian community.

Oral cancers and other squamous cell cancers of the head and neck are common cancers in India, primarily due to tobacco chewing/smoking and alcohol consumption. Recent reports indicate involvement of human papillomavirus (HPV), HPV 16, in a subset of squamous cell carcinoma of head and neck (SCCHN) cases. To investigate the types of HPVs present in 83 oral cancers and 19 other head and neck tumors, degenerate primers directed to consensus regions in the HPV L1 open reading frame (ORF) were employed to amplify genomic DNA from tumor and when available, the adjacent normal mucosa. PCR-amplified products were cloned and sequenced. Similar studies were done on exfoliated buccal cells of 102 individuals visiting a dental hospital for dental complaints. HPV was detected in 32 out of 102 patients (31%), in either the tumor or the adjacent normal mucosa, while 5% (5/102) of the comparative group were found to be HPV-positive. Sequence analysis revealed a number of cutaneous HPVs, predominantly HPV types of the genus Beta-Papillomavirus, in the oral cavity. Multiple HPV infections were also commonly observed in patients (14/102; 14%). HPV 16 and 18 were each detected in 6 patients (6/102; 6%). Neither high-risk HPVs nor multiple infections were observed in the mouthwash samples of the comparative group. We report that the oral cavity harbors a variety of different HPVs. These viruses, in conjunction with the carcinogens present in tobacco could contribute to carcinogenesis.

Adult↗

PubMed2001

Bacterial aerosols in the dental clinic: a review.

A number of sources of bacterial aerosols exist within and outside the dental clinic. The concentration of bacterial aerosols and splatters appears to be highest during dental procedures, especially those generated by some procedures such as ultrasonic scaling, or using a high speed drill. Several infectious diseases could be transmitted to staff and patients by airborne bacterial and other contaminants in the dental clinic. Air-conditioning and ventilation systems should be regularly maintained to reduce environmental contaminants and to prevent recirculation of bacterial aerosols. Pre-procedural rinsing by patients with mouthwashes as well as vacuum and electrostatic extraction of aerosols during dental procedures could also be employed. Dental staff should also consider appropriate immunizations and continue to use personal protective measures, which reduce contact with bacterial aerosols and splatters in the dental clinic.

Aerosols↗

PubMed2006

Low incidence of sepsis due to viridans streptococci in a ten-year retrospective study of pediatric acute myeloid leukemia.

BACKGROUND: Infections remain an important cause of morbidity and mortality in children with acute myeloid leukemia (AML), and particularly viridans group streptococci (VGS) sepsis. The present study, conducted between 1993 and 2003 in children with AML, sought to assess the frequency and characteristics of infectious complications (ICs), the incidence of VGS sepsis, the interest of preventive decontamination, and a possible cytarabine dose-effect on the occurrence of ICs. METHODS: Medical charts of 78 children treated according to the EORTC 58921 clinical trial were analyzed retrospectively. Patients were isolated in laminar air flow rooms, received non-absorbable gut decontamination, gum decontamination with vancomycin mouthwash, and trimethoprim-sulfamethoxasole. ICs were categorized as microbiologically documented infections (MDI), clinically documented infections (CDI), or fever of unknown origin (FUO). RESULTS: Overall, 268 ICs occurred: 57.5% FUO, 8.5% CDI, and 34% MDI. Bloodstream infections occurred in 58 febrile episodes: Gram-positive bacteria represented 83% of the pathogens including 66.1% Staphylococcus species and 8.5% Streptococcus species (6.8% VGS), Gram-negative bacteria represented 13.5% of the pathogens and yeasts 3.5%. Five patients died of infection (6.4%). None died from bacterial infection and no case of VGS sepsis required intensive care. Invasive fungal infection was proven in four patients. Number of ICs was significantly different according to gum and gut decontamination status, and according to the cytarabine dose during the first intensification. No resistant strains were detected in spite of the use of local antibiotics. CONCLUSION: The low rate of VGS and enterobacteriaceae sepsis was probably due to the effective decontamination. Our supportive care strategy could potentially help enhance overall survival in children with AML.

Acute Disease↗

PubMed1999

Structural basis and mechanism of enoyl reductase inhibition by triclosan.

The enoyl-acyl carrier protein reductase (ENR) is involved in bacterial fatty acid biosynthesis and is the target of the antibacterial diazaborine compounds and the front-line antituberculosis drug isoniazid. Recent studies suggest that ENR is also the target for the broad-spectrum biocide triclosan. The 1.75 A crystal structure of EnvM, the ENR from Escherichia coli, in complex with triclosan and NADH reveals that triclosan binds specifically to EnvM. These data provide a molecular mechanism for the antibacterial activity of triclosan and substantiate the hypothesis that its activity results from inhibition of a specific cellular target rather than non-specific disruption of the bacterial cell membrane. This has important implications for the emergence of drug-resistant bacteria, since triclosan is an additive in many personal care products such as toothpastes, mouthwashes and soaps. Based on this structure, rational design of triclosan derivatives is possible which might be effective against recently identified triclosan-resistant bacterial strains.

Anti-Bacterial Agents↗

PubMed2002

Toxicological studies on Laccase from Myceliophthora thermophila expressed in Aspergillus oryzae.

The bioindustrially produced enzyme laccase can be used in different technical and food applications to facilitate processes. It can be added to different oral care products such as mouthwash, toothpaste, mints, and gums to prevent halitosis. Laccase, produced by submerged fermentation of Aspergillus oryzae, containing a gene originating from Myceliophthora thermophila, was subject to a series of toxicological tests to document its safety in use. It was not found to be mutagenic in the Salmonella typhimurium reverse mutation assay, nor did it cause chromosomal aberrations in cultured human lymphocytes. No evidence of inhalation toxicity or skin and eye irritation was found. There was no evidence of possible skin sensitization in a human skin sensitization test when Laccase was tested at 10% (w/v): thus Laccase would appear to have a low skin sensitization potential. Oral administration to rats of up to 10.0 mL/kg body wt/day (equivalent to a total organic solids dosage of 1.72 g/kg body wt/day) for 13 weeks did not cause any adverse effect.

Administration, Inhalation↗

PubMed1979

Methotrexate-induced oral mucositis and salivary methotrexate concentrations.

We examined the plasma and saliva levels of methotrexate (MTX) achieved during the treatment and rescue periods of ten patients receiving 42-h MTX infusions followed by citrovorum rescue. Saliva MTX levels were generally 1%--2% of the simultaneous plasma levels. Four patients developed severe oral mucositis; three patients developed mild to moderate oral toxicity, and three others had no evidence of mucositis. MTX levels in the patients with severe mucositis were not higher and did not persist longer than the levels achieved in patients with mild or absent toxicity. Attempts at reducing the severity of oral mucositis with topical citrovorum mouthwashes or with atropine to suppress salivation were unsuccessful. MTX-induced oral mucositis is not related to salivary MTX concentrations, and the use of topical citrovorum therapy or the suppression of salivation does not appear to ameliorate this toxicity.

Humans↗

PubMed1995

HTLV-I from Iranian Mashhadi Jews in Israel is phylogenetically related to that of Japan, India, and South America rather than to that of Africa and Melanesia.

A new endemic focus of human T-lymphotropic virus type I (HTLV-I) was recently reported among Mashhadi Jews, a group of immigrants from northeastern Iran to Israel. We extracted DNAs from fresh peripheral blood mononuclear cells (PBMCs) and/or gargle mouthwash from 10 HTLV-I carriers, who consisted of members of one family, and HTLV-I-associated myelopathy (HAM) and adult T-cell leukemia (ATL) patients. Long terminal repeat (LTR) regions of proviral DNAs were sequenced and analyzed phylogenetically. In a phylogenetic tree, all the Mashhadi HTLV-I isolates belonged to subtype A, one of the three subtypes of the cosmopolitan type of HTLV-I, and made a tight cluster distinct from the other isolates of subtype A from Japan, India, the Caribbean Basin, and South America. Although a few nucleotide substitutions were observed among the clones sequenced, no characteristic sequence variation was found in different disease manifestations, even in one family or different sources of DNA preparation.

Adult↗

PubMed1994

Controlled study of fluconazole in the prevention of fungal infections in neutropenic patients with haematological malignancies and bone marrow transplant recipients.

The efficacy and safety of oral fluconazole versus a polyene regimen in preventing mycoses in neutropenic patients was compared. Patients with haematological malignancy or bone marrow transplantation received as antifungal prophylaxis either fluconazole 200 mg daily or a regimen consisting of clotrimazole trouches 10 mg twice daily with mycostatin, 500,000 I.U. four times daily, benadryl and cepacol mouthwash. Ninety patients at risk for fungus infection were evaluable. Four of 42 patients (9.5%; confidence interval 2%-23%) on fluconazole and 17 of 48 patients (35.4%; confidence interval 22%-52%) (p < 0.01) on the clotrimazole regimen developed a clinically significant fungal infection, including 3 (7.1%) and 11 (22.9%) patients respectively who had severe fungal infection, mainly pulmonary aspergillosis. Death directly due to a fungal infection within 100 days of the start of prophylaxis occurred in 2 of 42 patients (4.8%) and 9 of 48 patients (18.8%) respectively (p < 0.06). Kaplan-Meier analysis showed that the chance of survival on fluconazole was statistically greater than for the clotrimazole regimen (p < 0.04). A decrease of candidal colonisation of the gastrointestinal and genitourinary tracts occurred only in patients receiving fluconazole. No significant toxicity occurred. A 200 mg daily dose of fluconazole given to these patients thus appears to be well tolerated and to provide a protective effect against the development of fungal infection and death from severe fungal disease.

Adolescent↗

PubMed2005

Adherence to simple and effective measures reduces the incidence of ventilator-associated pneumonia.

PURPOSE: Several modalities have been shown to be individually effective in reducing the incidence (and hence associated morbidity, mortality, and costs) of ventilator-associated pneumonia, but their implementation into clinical practice is inconsistent. We introduced an intensive care unit protocol and measured its effect on ventilator-associated pneumonia. METHODS: A multidisciplinary team constructed a multifaceted protocol incorporating low risk and low cost strategies, many of which had independent advantages of their own. Some components were already in use, and their importance was emphasized to improve compliance. New strategies included elevation of the head of the bed, transpyloric enteral feeding, and antiseptic mouthwash. The approach to implementation and maintenance included education, monitoring, audits and feedback to encourage compliance with the protocol. RESULTS: The implementation of this prevention protocol reduced the incidence of ventilator-associated pneumonia from a baseline of 94 cases per year or 26.7 per 1,000 ventilator days to 51.3 per year or 12.5 per 1,000 ventilator days, i.e., about 50% of the pre-protocol rate (P < 0.0001). CONCLUSION: Adherence to simple and effective measures can reduce the incidence of ventilator-associated pneumonia. The protocol described was inexpensive and effective, and estimated savings are large. Implementation and maintenance of gains require a multidisciplinary approach, with buy-in from all team members, and ongoing monitoring, education, and feedback to the participants.

Hospital Mortality↗

PubMed1997

[The therapeutic management of radiogenic oral mucositis].

BACKGROUND: Acute reactions of oral mucosa are a frequent side effect of radiotherapy, which often necessitates interruption of the treatment. Marked proliferation of tumor stem cells during treatment interruptions may occur in squamous cell carcinomata, which represent the majority of tumors in the head and neck area. Hence a fatal consequence of treatment breaks may be a significant decrease in tumor cure rates. Furthermore, marked acute responses frequently result in increased late sequelae ("consequential damage"). Therefore, amelioration of the mucosal response aiming at avoiding treatment breaks and at reduction of late reactions could definitely increase the therapeutic success of radiation treatment. PATIENTS AND METHOD: Various possibilities for the therapeutic management of radiation-induced oral mucositis with a symptomatic or radio- and epithelial biological background are summarized and presented systematically. RESULTS: A variety of prophylactic and therapeutic methods have been proposed for the management of acute radiation reactions of the oral mucosa. Frequently, their efficacy has been established for chemotherapy or in combination with other immunosuppressive treatments. Hence, systematical rather than local effects have to be considered. CONCLUSIONS: In general, prophylaxis of oral mucositis is mainly based on dental restoration or edentation, in combination with frequent oral hygienic measures after the meals and with antiseptic mouthwashes. Intensive personal care is recommended. The necessity of a percutaneous endoscopic gastrostoma is dependent on the status of the patient and on size and localization of the treatment area, i.e. the impairment of food uptake which is to be expected. Therapeutic intervention is restricted to local or systemic treatment of pain and local application of antimycotics and antibiotics.

Acute Disease↗

PubMed2006

Biomechanical muscle properties and angiotensin-converting enzyme gene polymorphism: a model-based study.

Previous studies reported an association of angiotensin-converting enzyme (ACE) I/D gene polymorphism with physical performance. The study was based on the hypothesis that certain individual biomechanical muscle properties could be associated with ACE genotype and that they could influence athletes' physical performance. Movement-independent individual biomechanical muscle properties of 62 sports students were determined by applying a mathematical model to experimental data. Subjects exerted concentric and isometric contractions at a leg-press. The model was based on a Hill-type muscle model, a function describing the geometrical arrangement of human leg extensor muscles, and an exponential function describing muscle activation. Mouthwash samples were taken to determine the ACE genotypes. Several combinations of experimentally determined biomechanical properties served as input variables for a discriminant analysis. We were able to show that individual biomechanical muscle properties correlated with ACE I/D gene polymorphism. With a combination of certain individual muscle parameters based on a Hill-type muscle model, we were able to separate three individual ACE genotypes (II, ID, DD) in a significant way (P<0.03) and correctly classify 89% of the cases using a discriminant analysis. We conclude that local biomechanical muscle properties are influenced by ACE genotype.

Adult↗

PubMed2002

Universal, robust, highly quantitative SNP allele frequency measurement in DNA pools.

Detecting alleles that confer small increments in susceptibility to disease will require large-scale allelic association studies of single-nucleotide polymorphisms (SNPs) in candidate, or positional candidate, genes. However, current genotyping technologies are one to two orders of magnitude too expensive to permit the analysis of thousands of SNPs in large samples. We have developed and thoroughly validated a highly accurate protocol for SNP allele frequency estimation in DNA pools based upon the SNaPshot (Applied Biosystems) chemistry adaptation of primer extension. Using this assay, we were able to estimate the difference in allele frequencies between pooled cases and controls (Delta) with a mean error of 0.01. Moreover, when we genotyped seven different SNPs in a single multiplex reaction, the results were similar, with a mean error for Delta of 0.008. The assay performed well for alleles of low frequency alleles (f approximately 0.05) and was accurate even with relatively poor quality DNA template extracted from mouthwashes. Our assay conditions are generalisable, universal, robust and, therefore, for the first time, permit high-throughput association analysis at a realistic cost.

DNA↗

PubMed2003

Analysis of zinc transporter, hZnT4 ( Slc30A4), gene expression in a mammary gland disorder leading to reduced zinc secretion into milk.

Zinc deficiency, causing impaired growth and development, may have a nutritional or genetic basis. We investigated two cases of inherited zinc deficiency found in breast-fed neonates, caused by low levels of zinc in the maternal milk. This condition is different from acrodermatitis enteropathica but has similarities to the "lethal milk" mouse, where low levels of zinc in the milk of lactating dams leads to zinc deficiency in pups. The mouse disorder has been attributed to a defect in the ZnT4 gene. Little is known about the expression of the human orthologue, hZnT4 (Slc30A4). Sequence analysis of cDNA, real-time PCR and Western blot analysis of hZnT4, carried out on control cells and cells from unrelated mothers of two infants with zinc deficiency, showed no differences. The hZnT4 gene was highly expressed in mouthwash buccal cells compared with lymphoblasts and fibroblasts. The hZnT4 protein did not co-localise with intracellular free zinc pools, suggesting that hZnT4 is not involved in transport of zinc into vesicles destined for secretion into milk. This observation, combined with phenotypic differences between the "lethal milk" mouse and the human disorder, suggests that the "lethal milk" mouse is not the corresponding model for the human zinc deficiency condition.

Adult↗

PubMed1997

Prevalence of delta F508 cystic fibrosis carriers in The Netherlands: logistic regression on sex, age, region of residence and number of offspring.

An average cystic fibrosis (CF) carrier frequency of 1 in 25 in Europe is cited in numerous reports, although a great variability in estimated prevalences has been found in different European populations. The estimates of these frequencies were based on numbers of CF patients before identification of the gene in 1989. Here we report the results of a study to determine the carrier frequency of the delta F508 mutation in The Netherlands by analyzing mouthwashes and matched blood samples from 11654 blood donors all over the country. We analyzed possible relationships between a number of theoretically explanatory variables and the delta F508 carrier frequency by means of univariate and multivariate logistic regression. These variables were: distance of the blood banks from the northeastern part of the country (distance); whether the blood donors knew that we were looking for a CF mutation; sex and age of the donor; and number of children of the donor (family size). We detected a delta F508 carrier frequency of 1 in 42 (95% CI 1/37-1/47) in The Netherlands. If we assume that the relative frequency of the delta F508 mutation among carriers and patients is comparable in The Netherlands, this gives an estimated overall CF carrier frequency of 1 in 32 (95% CI 1/28-1/36), significantly less than 1 in 25. The univariate logistic regression analysis of the effects of the explanatory variables on the carrier frequency revealed no significant relationships, except for an increase in carrier frequency with increasing distance from the northeastern region. In the multivariate analysis with all five independent variables, distance, age and family size were significantly related to the carrier frequency, but sex and CF information were not. There was a significant interaction between age and family size. In our final model, distance, age and family size were positively related to the carrier frequency, while the interaction of age with family size showed a negative relation. These results confirm that there is a gradient in gene frequency with low frequencies in the northeastern part of the country and high frequencies in the southern part. They also suggest a relation of age and family size with carrier frequency. This relation, however, is too complex to be explained by heterozygote advantage.

Adolescent↗

PubMed2005

Oro-dental health in children with chronic renal failure and after renal transplantation: a clinical review.

As a consequence of chronic renal failure (CRF) and its treatment, a number of oro-dental changes occur that persist after the end-stage is reached. An early effect is enamel hypoplasia due to a defect of enamel development and mineralisation. This is usually reparable to a high aesthetic standard using dental composite filling material. Children with CRF have significantly less dental caries than healthy children due to the inhibitory effect of increased salivary urea levels. Grafted patients frequently develop gingival enlargement as a result of immunosuppression with cyclosporine A, which is further exacerbated by the additional use of antihypertensive calcium-blocking agents. Surgical reduction of gingival hyperplasia is effective and is required in approximately one third of adolescents. A very high standard of home care should be encouraged for all children with CRF in the form of thorough mechanical tooth cleaning and plaque inhibition through the use of an antibacterial mouthwash. In transplanted children presenting an increased risk of infection, antibiotic prophylaxis may be indicated for dental treatment procedures. The drug dosage should be adapted to the reduced renal function. Pediatric nephrologists should be aware that dental surgeons can make a considerable contribution to the general health and well-being of children with CRF. Thus, only oro-dental problems that are mainly encountered and treated by dental surgeons are reviewed.

Adolescent↗

PubMed2000

A survey of mouth pain and dryness in patients with advanced cancer.

An 11-item face-to-face survey was conducted in 99 consecutive patients with advanced cancer to determine the prevalence, intensity, reporting and treatment, presumed cause(s), and importance of mouth pain and dryness. Sixteen of the 99 patients (16%) reported experiencing mouth pain at a mean intensity corresponding to 5.5 +/- SD 2.21 on a 0 (no pain) to 10 (worst possible pain) numerical scale, and 88 (88%) patients reported dry mouth at a mean intensity corresponding to 6.2 +/- SD 2.21. Nine (56%) of the 16 patients with mouth pain and 39 (44%) of the 88 patients with mouth dryness reported these symptoms to their attending physician(s). Sixty-nine percent (27/39) of patients who reported having a dry mouth were advised by their physician(s) to pursue one or more treatments. The most common treatments recommended (and frequencies) were drinking water/taking sips of fluid (13), gargling with bicarbonate mouthwash (4), using an artificial saliva spray (4), and using an oral fungal suspension for thrush (4). The most common findings on oral examination included: possible thrush (53 patients), upper and lower dentures (33 patients), and multiple dental restorations (23 patients). The causes most frequently assumed to be responsible were ill-fitting dentures for mouth pain, and medications and possible oral fungal infections for mouth dryness. The mean values given for the importance of the symptoms of mouth pain and dryness relative to other symptoms or problems experienced by the patients were 4.4 +/- SD 1.84 and 3.6 +/- SD 1.67, respectively, on a Likert scale ranging from 1 (not important) to 7 (great importance). Mouth dryness was more frequently reported than mouth pain. The mean rating for the intensity of mouth pain was higher than that for mouth dryness, although both were of moderate importance to patients relative to other symptoms or problems experienced at the time. Patients tended to underreport mouth pain and dryness, and physicians tended to address such complaints inadequately.

Adult↗

PubMed2000

The cancer patient with severe mucositis.

Oropharyngeal mucositis is a painful, often dose-limiting side effect of both radiotherapy and chemotherapy. To reduce the intensity of pain and prevent systemic infection via the compromised mucosa, agents such as antiseptic mouthwashes, anti-ulcer compounds, sodium bicarbonate, saline, and allopurinol have been traditionally used with limited success. The new agents that show promise are granulocyte macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF). However, best results, dosage, and means of administration still have to be determined. Other agents such as sucralfate, tretinoin, glutamine, and misoprostol are also being tested. The results reported from different testing centers are often contradictory and confusing. Basic requirements in prevention and control of mucositis are good oral hygiene, mechanical débridement of the oral tissues, and hydration.

Granulocyte-Macrophage Colony-Stimulating Factor↗