Periodontal medicine in the next millennium.

Dentistry and medicine have, to a great extent, been somewhat separated during the last 160 years, despite the fact that they have the same patients in common. We have now reached a period in our history when research is bringing medicine and dentistry closer together with data that are cogent to physicians and dentists and, most importantly, to the patient. A new paradigm is emerging with regard to susceptibility to periodontal disease, its etiology, and pathogenesis. Definite relationships between the oral disease and systemic conditions show that some risk factors are a concern for periodontal disease and certain systemic diseased such as cardiovascular disease. Periodontal diseases and systemic diseases--this is a two-way street. It is becoming clear that the dentist needs to know more about systemic diseases, and the physician needs to increase his or her knowledge of oral diseases. We may see an increase in oral microbiology testing for patients with periodontal disease. We also will see more dentists doing glucose testing as well as other tests in their practices. Physicians and dentists working more closely together, more patients with systemic diseases will be managed more successfully, and patients will benefit from predictable treatment regimens to save their dentition.

Advancing women and closing the leadership gap: the Executive Leadership in Academic Medicine (ELAM) program experience.

Women are persistently underrepresented in the higher levels of academic administration despite the fact that they have been entering the medical profession in increasing numbers for at least 20 years and now make up a large proportion of the medical student body and fill a similar proportion of entry level positions in medical schools. Although there are no easy remedies for gender inequities in medical schools, strategies have been proposed and implemented both within academic institutions and more broadly to achieve and sustain the advancement of women faculty to senior level positions. Substantial, sustained efforts to increase programs and activities addressing the major obstacles to advancement of women must be put in place so that the contributions of women can be fully realized and their skills fittingly applied in meeting the medical education and healthcare needs of all people in the 21st century.

Expression of c-kit and kit-ligand in benign and malignant prostatic tissues.

The tyrosine kinase receptor c-kit and its ligand [kit ligand (KL) or stem cell factor (SCF)] exert a broad range of biological activities during organogenesis and normal cell development. Recent studies have revealed that altered c-kit levels occur in a variety of malignancies and cancer cell lines. KL has also been shown to stimulate the growth of malignant cells, as well as to promote chemotaxis. We had previously reported expression of KL in stroma cells of normal human prostate. The present study was undertaken in order to analyze the patterns of expression of c-kit and KL in a well characterized set of prostatic tissues, including normal prostate (n=4), benign prostatic hyperplasia (BPH) (n=53) and adenocarcinoma (n=46) samples. The distribution of c-kit and KL proteins was studied by immunohistochemical analyses, while transcript levels were determined by in situ hybridization with specific RNA probes on a subset of the benign and malignant tissues referred above. In addition, reverse-transcriptase polymerase chain reaction (RT-PCR) was performed to determine levels of c-kit and KL expression in cultures of epithelial and stroma cells, as well as in the prostate cancer cell lines LNCaP, DU145 and PC3. c-kit protein in normal prostate was exclusively detected in mast cells by immunohistochemistry and in situ hybridization. However, c-kit transcripts, but not c-kit protein, were detected in low levels and with an heterogeneous pattern in basal epithelial cells of ducts and acini. c-kit in BPH was detected in epithelial cells in 9 of 53 (17%) specimens. c-kit protein expression in malignant epithelial cells was identified in 1 of 46 (2%) tumors. However, c-kit transcripts were detected in low levels by in situ hybridization in most of the tumors analyzed. KL protein and transcripts in normal prostate were detected in high levels in stroma cells. However, epithelial cells were unreactive for anti-KL antibody, but showed low levels of KL transcripts mainly in cells of the basal layer. Basal epithelial cells in hyperplastic glands showed KL expression in 13 of 53 (24%) specimens. KL protein in tumor cells was noted in 18 of 46 (39%) cases. c-kit transcripts were not found in normal prostate and in the 3 cancer cell lines analyzed by RT-PCR, however, it was present in cultured epithelial cells of BPH, and in cultures of stroma cells from both normal and BPH. The majority of cultured cell lines of epithelial and stromal origin displayed considerable levels of KL. In addition all prostate cell lines studied showed significant levels of KL transcripts. In summary, co-expression of c-kit and KL in a subset of BPH cases may suggest an autocrine mode of signaling. Data from this study reveals that altered patterns of c-kit and KL expression are associated with BPH and adenocarcinoma of prostate. It appears that KL induces mast cells proliferation and maturation and enhances their release of protease. This could explain the accumulation of mast cells at tumor sites, a phenomenon that was not observed in normal prostate or BPH samples.

The relationship of beta-glucuronidase activity in crevicular fluid to probing attachment loss in patients with adult periodontitis. Findings from a multicenter study.

Analysis of gingival crevicular fluid (GCF) offers a non-invasive means of studying the host response in periodontal disease, and may provide an early indication of the patient at risk for active periodontitis. A number of host markers have been studied for their relationship to disease activity (probing attachment loss or PAL). GCF levels of the acid glycohydrolase beta-glucuronidase (beta G), a marker of primary granule release from polymorphonuclear leukocytes (PMN), have been shown to identify patients with periodontitis at risk for additional PAL. In this multicenter trial, we evaluated (a) the short-term effect of conservative periodontal therapy on beta G activity in GCF, and (b) the relationship of persistently elevated beta G activity to PAL in patients who were monitored for 6 months. The study population included a total of 140 patients with chronic adult periodontitis. 130 patients were on a regular recall schedule, and 10 were previously untreated. After collection of baseline clinical data at all sites, and analysis of beta G in GCF from one site (mesiobuccal) per tooth, the patients received a scaling and prophylaxis. Two weeks later patients were seen for collection of GCF. If elevated enzyme activity was found at 2 weeks, the patients were seen at 3 months for a clinical exam and GCF collection. Clinical parameters were collected from all patients at 6 months. Therapy tended to reduce beta G activity in GCF.(ABSTRACT TRUNCATED AT 250 WORDS)

Expression of transforming growth factor-alpha and the epidermal growth factor receptor in human prostate tissues.

Cells respond to certain soluble factors that bind to cell surface receptors possessing intrinsic tyrosine kinase activity. Overexpression of these molecules has been associated with tumor progression. Enhanced prostatic cancer cell growth in vitro has been reported in the presence of certain growth factors. To characterize the patterns of expression of the epidermal growth factor receptor (EGFr) and transforming growth factor-alpha (TGF alpha), we studied tissue from 107 prostate specimens using immunohistochemistry. We observed that epithelial cells of normal (n = 4) and benign prostatic (n = 56) tissues express EGFr but were unreactive for TGF alpha, while stroma cells in these tissues express TGF alpha but not EGFr. However, coexpression of EGFr and TGF alpha was identified in 22 of 46 prostatic adenocarcinomas studied. These results suggest that the major mode of action of EGFr/TGF alpha in normal and benign prostate is that of a paracrine or juxtacrine loop, the ligand being expressed in the stroma cells and the receptor in the epithelial cells. Since a subset of prostatic carcinomas coexpressed the ligand and the receptor in their tumor cells, it is suggested that an independent autocrine signaling mechanism may occur and grant a selective advantage for the growth of prostate cancers.

Clinical and pathobiological effects of neoadjuvant total androgen ablation therapy on clinically localized prostatic adenocarcinoma.

Neoadjuvant total androgen ablation therapy leads to involutional changes in prostatic carcinoma and may have the potential to downstage operable prostate cancers. We studied 27 clinically localized prostatic carcinomas after 3 months of combined treatment with a luteinizing hormone-releasing hormone agonist, goserelin acetate, and the antiandrogen flutamide, followed by radical retropubic prostatectomy, for changes in the serum prostate-specific antigen (PSA) level, changes in prostatic volume, therapy-induced histopathologic changes, DNA ploidy, and proliferative activity. Ten hormonally untreated, grade-matched prostatic adenocarcinomas served as controls. The mean pretherapy serum PSA level was 17.5 ng/ml, and posttherapy PSA levels were all < 4.0 ng/ml, with 18 men having undetectable levels. The mean reduction in prostatic volume following hormonal therapy was 37% (range 16-52%). Pathologic staging confirmed 20 pT2N0, six pT3N0, and one pT3N1. All prostates showed residual adenocarcinoma (extremely focal in seven cases [26%] with loss of glandular architecture, cytoplasmic vacuolization, and nuclear pyknosis. High-grade adenocarcinoma was nondiploid in 25% of hormonally treated prostates and 80% of 10 untreated controls. Immunostaining for proliferating cell nuclear antigen showed > 10% nuclear reactivity in 33% of treated carcinomas and 90% of untreated carcinomas. In conclusion, 3 months of neoadjuvant androgen ablation for localized prostatic carcinoma significantly lowers serum PSA and prostatic volume and produces involutional changes in residual carcinomas that mimic high-grade disease. However, pretreated carcinomas have predominantly a diploid DNA content and low proliferative activity as opposed to untreated carcinomas. Thus, grading of pretreated adenocarcinomas by conventional methods may be misleading. Preoperative total androgen ablation has a profound effect on a subset of prostatic carcinoma cells, possibly by facilitating programmed cell death.

The relationship of beta-glucuronidase activity in crevicular fluid to clinical parameters of periodontal disease. Findings from a multicenter study.

Previous reports have suggested that persistently elevated levels of the acidic glycohydrolase beta-glucuronidase (beta G) in gingival crevicular fluid (GCF) can identify patients with chronic adult periodontitis who are at risk for future probing attachment loss (PAL). To comprehensively study beta G activity in GCF, a multicenter trial examining the relationship of the enzyme in GCF to traditional clinical parameters of periodontal disease and PAL was conducted. In this report, the baseline data was used to evaluate the relationship of beta G activity in GCF to traditional parameters of periodontal disease. The study group included 130 patients who had been treated for periodontal disease and were on a regular recall schedule, and 10 patients with chronic adult periodontitis who had never received treatment. Upon entering the longitudinal trial, the patients were examined, and a standardized 30-s GCF sample was collected from the mesiobuccal crevice of all study teeth. As a control, GCF samples and clinical data were collected from 62 patients with a healthy periodontium or mild inflammatory gingivitis without loss of probing attachment. At baseline, beta G activity for the periodontitis patients ranged from 0 to 1704 Units (U), with a median of 32 U. beta G could not be detected in 0.2% of samples (activity < or = 2.0 U). The 90% cumulative relative frequency was 139 U. For the healthy/gingivitis subjects beta G activity ranged from 0 to 504 U, with a median of 22 U. Enzyme was not detectable in 0.4% of samples. Only 0.9% of samples contained greater than 139 U. beta G activity in GCF was not related to gender or age. For the periodontitis patients, elevated enzyme activity (> or = 140 U) was most often associated with molar teeth, followed by maxillary bicuspids. Maxillary central incisors, and mandibular central and lateral incisors displayed the lowest frequency of elevated enzyme activity. The relationship of beta G activity to the traditional parameters of probing depth and bleeding on probing was assessed. For shallow sites (1.0-1.5 mm, 2.0-2.5 mm probing depth), the large majority of GCF samples contained low enzyme activity (90% of samples < 50 U). Descriptive indicators demonstrated a trend of increased beta G activity with increased probing depth. The median beta G activity shifted from 15 U for the shallowest sites (1.0-1.5 mm) to 127 U for the deepest sites (5-8 mm). However, this was due to a broadening of the distribution rather than representing a shift in the distribution profile.(ABSTRACT TRUNCATED AT 400 WORDS)

Chlorhexidine gluconate in periodontal treatment.

Dr. Henry M. Goldman's contributions to periodontics are many, but none may be as significant as the work he did in the study of antimicrobial agents used to fight periodontal disease. This article presents a review of the literature on antimicrobial effectiveness of chlorhexidine gluconate and describes its role as a chemotherapeutic, antibacterial, antiplaque agent.

The future of dental education.

This paper reviews the highlights of some of the current literature on the future of dental education and also focuses on a 10-year follow-up on certain aspects of the Pennsylvania Experiment.

Successful periodontal treatment for the elderly.

The demographic reality of a rapidly growing elderly population segment presents the practicing dentist with certain imperatives and challenges. Familiarity with the healthy aging process and common medical conditions of the aged is becoming increasingly essential. Customized treatment plans and modifications in techniques and home care aids require flexibility and creativity. In addition, it should not be overlooked that this demographic reality also presents the practicing dentist with new opportunities for practice-building as well as personal and professional satisfaction.

Periodontal considerations in preparation for fixed and removable prosthodontics.

This article has presented many of the newer concepts and techniques that have been developed to treat a problem that has been of major concern to the prosthodontist: the problem of favorable periodontal support and poor or deformed edentulous ridges. In the past, dentists were not aware, or did not believe, that it was possible to reconstruct ridge deformities, and they resorted to prosthetic solutions to solve the problems of tissue reconstruction, function, and aesthetics. New procedures and concepts permit us to extend the range of therapy and hope we are able to offer our patients. It is probably true that prosthodontists are more sensitive to the emotional concerns and needs of patients that have sustained ridge-jaw deformities. These patients bear deep emotional scars. They feel cast apart from "normal" society. Successful treatment for these patients not only restores their deformed ridge and dentition, it helps to erase the mental scars and emotional trauma these patients have had to accept. These procedures enable us to restore their sense of self-confidence and dignity.