Serial doxycycline and metronidazole in prevention of recurrent periodontitis in high-risk patients.

The efficacy of metronidazole and doxycycline in preventing recurrent periodontitis was studied in 23 patients. After treatment in the previous 7 months with either bimonthly scaling and 3 weeks of systemic doxycycline (11 subjects) or scaling and placebo (12 subjects), patients were monitored for recurrent periodontitis and were scaled every 2 months. When either a periodontal abscess or greater than 2 mm loss of gingival attachment was observed, metronidazole was administered (250 mg every 8 hours) for 10 days. In the placebo plus metronidazole group, 5 patients (42%) exhibited recurrent periodontitis after the metronidazole regimen compared with only one (9%) in the doxycycline plus metronidazole group (P less than 0.096). Subgingival plaque samples at study and healthy control sites were screened for the presence of Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia, Eikenella corrodens, and Fusobacterium nucleatum by immunofluorescence and for spirochetes using Ryu's stain. Presence/absence analysis of the sum of scores of the 6 individual pathogens demonstrated large reductions (P less than 0.005) in the frequency of detection of pathogens in the former doxycycline compared with the placebo plus metronidazole group at both study and control sites before and one month after metronidazole. By 7 months after metronidazole, there was no detectable difference between groups. These results indicate that prevention of recurrent periodontitis with metronidazole may be enhanced by previous treatment with doxycycline.     

Therapy of metabolic disorders with intravenous (IV) access ports and long term intravenous L-carnitine therapy

With the expansion of newborn screening to include many organic acidurias and fatty acid oxidation defects, effective therapies of these disorders will be needed. Currently severe disorders such as methylmalonic and propionic aciduria. conventional therapy with diet and oral L-camitine often prove ineffective in preventing failure to thrive and recurrent metabolic decompensations. L-carnitine provides a natural pathway for removal of the toxic metabolites in these disorders and is life saving therapy but, with poor oral absorption (25%), it is difficult to supply adequate carnitine to meet the metabolic needs of these patients. Long term intravenous L-carnitine therapy, administered through a subcutaneous venous access port in 5 patients with organic acidurias [propionic aciduria (2), methylmalonic aciduria (2), 3 methylglutaconic aciduria(1)] resulted in improved growth, lower frequency of metabolic decompensations and increased tolerance of natural protein in the diet. An added benefit was the ability to initiate fluid. electrolytes, and antibiotics during metabolic decompensations at home thus averting hospitalizations.     

Are nicotine replacement strategies to facilitate smoking cessation safe?

Professional obligations to curb the prevalence of cigarette smoking reflect the importance of this preventable risk factor for innumerable diseases. These include chronic obstructive pulmonary disease and oral, lung and other cancers, although the morbidity and mortality rates for cerebrovascular disease (e.g., ischemic strokes) and cardiovascular disease (e.g., ischemic myocardial infarction) tend to be greater. Various alternative nicotine sources (e.g., transdermal nicotine patches, nicotine gum, nicotine nasal sprays) have been incorporated into smoking cessation programs. This review is intended to increase professional awareness of nicotine delivery systems available in Canada, including safety considerations. The pathogenic potential of nicotine, regardless of source, and the contraindications to the use of nicotine replacement therapies are discussed. However, the systemic nicotine load in individuals undergoing replacement therapy is generally lower than during active smoking. Nicotine is only one of many thousands of constituents of tobacco smoke. Furthermore, nicotine replacement is usually delivered over the short term (a matter of weeks). Therefore, nicotine replacement is recognized as a relatively safe and effective aid to smoking cessation.     

Detection of Helicobacter pylori in oral aphthous ulcers

A causative role for Helicobacter pylori (H. pylori) in the pathogenesis of oral mucosal ulcerations has been suggested previously. We have adopted the polymerase chain reaction (PCR) as a rapid and sensitive means to detect H. pylori in swabs of recurrent oral aphthous ulcers and in samples of other oral sites. Of the oral aphthous ulcer samples, 32 (71.8%) were found to be positive, while the saliva and plaque samples (most of them taken from the patients with aphthous ulcers) were consistently negative for H. pylori DNA, as detected by the PCR assay. Only two of the swab samples from the tongue (collected at the time of concurrent, H. pylori-positive oral aphthous ulcers) were found to be positive. The data suggest that H. pylori may be associated frequently with recurrent oral aphthous ulcers, and are consistent with previous studies indicating that saliva and plaque are not likely sources of contamination with this microorganism. There was no apparent correlation with HIV status (infection with human immunodeficiency virus). The possible pathogenic significance of Helicobacter pylori in oral ulcerations is discussed.     

EBV and HSV infections in a patient who had undergone bone marrow transplantation: oral manifestations and diagnosis by in situ nucleic acid hybridization

The course of infections with herpes simplex virus and Epstein-Barr virus in an immunosuppressed patient who had undergone bone marrow transplantation and had tested seronegative for human immunodeficiency virus is described. The clinical oral manifestations were unusual, as they included hairy leukoplakia-like lesions and extensive mucosal ulceration. Histologic examination disclosed unique features consisting of both lichenoid and viral cytopathic changes. The association of the lesions with both Epstein-Barr virus and herpes simplex virus was confirmed by in situ hybridization histochemistry. The importance of recognition of the symptoms, specific diagnosis by DNA hybridization, and implications for antiviral prophylaxis and therapy are emphasized.     

Neoplastic transformation of osteogenic cells: quantitative morphometric analysis of an in vitro model for osteosarcoma

Previously we have reported the development of a model in vitrosystem for the study of osteosarcoma. In this system, when chickperiosteal explants are infacted with Fujinami sarcoma virus(FSV), osteosarcoma-like tissue is formed. In the present study,a series of histopathologic parameters of neoplastic transformationand osteogenesis were quantitated, at a single cell level, bycomputer-assisted morphometry. Most significantly, it was foundthat compared to uninfected (control) cultures, in the FSV-infected(experimental) Cultures, the bone to osteoid ratio per unitarea was decreased due to a relative decrease in the area ofbone and an increase in the area of osteoid. The cellularityof the FSV-infected tissues was significantly increased dueto an increase in the number of unlabeled and [³H]thymidine-labeledcells, while the proportion of alkaline phosphatase (AP) positivecells decreased. Double-label immunohistochemistry (with anti-P140^gag-fps)and histochemistry for AP activity was performed, to demonstrateproduction of the oncogene-encoded protein, and osteoblasticdifferentiation respectively. In an in vitro transformationassay, single cells derived from control, uninfected culturesdid not grow, while those derived from FSV-infected culturesformed colonies in semisolid medium. Some of these coloniesdemonstrated AP staining. Taken together these data show thatin this in vitro system (i) neoplastic transformation of osteogeniccells does occur, (ii) changes in osteoid and bone productionare related to neoplastic transformation, and (iii) ostepsarcoma-likechanges can be quantitated at the individual cell level.     

Gain of 11q/cyclin D1 overexpression is an essential early step in skin cancer development and causes abnormal tissue organization and differentiation

Non-melanoma skin cancers, in particular keratoacanthomas (KAs) and squamous cell carcinomas (SCCs), have become highly frequent tumor types especially in immune-suppressed transplant patients. Nevertheless, little is known about essential genetic changes. As a paradigm of 'early' changes, that is, changes still compatible with tumor regression, we studied KAs by comparative genomic hybridization and show that gain of chromosome 11q is not only one of the most frequent aberration (8/18), but in four tumors also the only aberration. Furthermore, 11q gain correlated with amplification of the cyclin D1 locus (10/14), as determined by fluorescence in situ hybridization, and overexpression of cyclin D1 protein (25/31), as detected by immunohistochemistry. For unraveling the functional consequence, we overexpressed cyclin D1 in HaCaT skin keratinocytes. These cells only gained little growth advantage in conventional and in organotypic co-cultures. However, although the control vector-transfected cells formed a well-stratified and orderly differentiated epidermis-like epithelium, they showed deregulation of tissue architecture with an altered localization of proliferation and impaired differentiation. The most severe phenotype was seen in a clone that additionally upregulated cdk4 and p21. These cells lacked terminal differentiation, exhibited a more autonomous growth in vitro and in vivo and even formed tumors in two injection sites with a growth pattern resembling that of human KAs. Thus, our results identify 11q13 gain/cyclin D1 overexpression as an important step in KA formation and point to a function that exceeds its known role in proliferation by disrupting tissue organization and thereby allowing abnormal growth.     

In vitro transformation of osteoblasts: putative formation of osteosarcoma in vitro

The study of bone cancer has been difficult in part due to a lack of appropriate in vitro osteosarcoma model systems. The development of such systems is essential if a clearer understanding of the biology of and mechanisms behind the formation and progression of bone cancers is to be obtained. We report here the development of an in vitro model system which demonstrates important characteristics generally associated with osteosarcoma. The chick periosteal osteogenesis model was infected with the Fujinami Sarcoma Virus (FSV) containing the v-fps oncogene which encodes for a P140gag-fps protein-tyrosine kinase. Under the appropriate conditions FSV infected cultures developed bone and cartilaginous tissues which showed histopathological findings consistent with osteosarcoma. Biochemical data indicating massive increases in alkaline phosphatase activity, protein content, 3H-Thymidine incorporation as well as expression of active P140gag-fps confirm that transformation has occurred in FSV infected cultures. This novel in vitro model system should prove most useful in the study of bone cancer.