Estrogen prevention of lacrimal gland cell death and lymphocytic infiltration

Previous studies have shown that ovariectomy causes necrosis of lacrimal acinar cells, apoptosis of plasma cells and gland lymphocytic infiltration. Both, lacrimal gland cell death and lymphocytic infiltration were prevented by androgen treatment. Since estrogens are removed by ovariectomy, and the synthetic estrogen diethylstilbestrol has been shown to affect some biochemical correlates of lacrimal secretion, the purpose of this study was to determine the effect of 17-beta-estradiol treatment on ovariectomy-induced cell death and lymphocytic infiltration. Sexually mature female New Zealand white rabbits (4-4.5 kg) were ovariectomized and divided into two groups. One group was treated with 0.5 mg kg(-1) per day 17-beta-estradiol, and the other group with vehicle alone. A third group of sham operated rabbits was used as controls and they also were treated with vehicle alone. Six days after surgery, the animals were euthanized, the lacrimal glands removed and processed for analysis of apoptosis as assessed by DNA fragmentation, and for morphological examination. DNA fragmentation was determined using the TUNEL assay and agarose gel electrophoresis. Sections were also stained for rabbit thymic lymphocyte antigen (RTLA), and rabbit CD18. Labelled nuclei and stained areas were quantified by automated densitometry. Ovariectomized rabbits showed a significant increase in the values for degraded DNA as a percent of total nuclear area (2.90+/-0.40%) compared to sham operated rabbits (0.73+/-0.22%). 17-beta-estradiol treatment in ovariectomized rabbits prevented the increase in DNA degradation. Examination of TUNEL assay at higher magnification (40x) confirmed previous studies showing that ovariectomy caused apoptosis of interstitial cells. Significant numbers of bulging cells of very pale appearance under light microscopy, also confirm previously identified necrotic cells in acinar regions. Treatment with 17-beta-estradiol prevented this necrosis. Increased numbers of RTLA(+) and CD18(+) interstitial cells were also evident after ovariectomy. 17-beta-estradiol treatment prevented the increase in the number of lymphoid cells. We confirmed previous observations that suggest that glandular atrophy observed after ovariectomy is likely to proceed by necrosis of acinar cells rather than apoptosis, and that ovariectomy triggers an inflammatory response in the gland. These results suggest that in addition to androgens, estrogens also seem to play a role to maintain lacrimal gland structure and function. A decrease in available estrogen levels could trigger both lacrimal gland apoptosis and necrosis, as well as lymphocytic infiltration. Although, the effect of estrogens in these experiments seems to be direct and not through androgens, the possibility of the role of an autocrine and/or paracrine factors, promoted by estrogen on lacrimal gland cells still needs to be investigated.     

Hereditary gingival fibromatosis: aggressive 2-stage surgical resection in lieu of traditional therapy

INTRODUCTION: Hereditary gingival fibromatosis (HGF) is a rare condition characterized by progressive enlargement of the gingiva. Most cases follow autosomal dominant genetics, with a reported incidence of 1 in 750,000. In addition to cosmetic concerns, the compromised oral cavity may cause difficulty with eating, speech, hygiene, and oral competence. In addition, social consequences can be dramatic, forcing patients to lead isolated, reclusive lives. Traditional therapy uses serial gingival resections ("quadrantectomies") with primary closure. However, this method is associated with frequent recurrence and additional resections. We report on a family of 12 siblings, 8 of whom, including monozygotic twins, are affected with HGF. We describe corrective surgery for 3 siblings, as well as their long-term follow-up. METHODS: Three sisters suffered from severe maxillary and mandibular gingival hyperplasia. All complained similarly of weight loss, difficulty with articulation, and social isolation. Physical examination revealed massive overgrowth of both maxillary and mandibular gingiva, as well as multiple ectopic teeth. Following diagnostic biopsy, all 3 patients underwent staged resections. The first stage involved resection of the maxillary component, followed by a planned second-stage resection of the mandibular component. All resections included gingivectomies, odontectomies, and alveolar ridge ostectomies. The oral cavity was allowed to heal by secondary intention. RESULTS: All 3 patients were female, and ages ranged from 34-48 years (mean: 43). Follow-up on the 3 patients ranged from 3-18 months (mean: 11 months). There has been no evidence of recurrence to date. The gingiva remucosalized uneventfully within several weeks, and all patients are tolerating solid food. All patients report dramatically improved speech, oral hygiene, and self-confidence. CONCLUSIONS: In an effort to address the high recurrence rate, we describe our aggressive surgical approach, including resection of the hypertrophied gingiva and alveolar processes. Two-staged gingival resection, as opposed to the more traditional 4-stage quadrantectomy approach, has resulted in no recurrence to date, suggesting an improved outcome over the traditional techniques.     

The impact of immediate breast reconstruction on the technical delivery of postmastectomy radiotherapy

PURPOSE: To quantify the impact of immediate breast reconstruction on postmastectomy radiation therapy (PMRT) planning. METHODS: A total of 110 patients (112 treatment plans) who had mastectomy with immediate reconstruction followed by radiotherapy were compared with contemporaneous stage-matched patients who had undergone mastectomy without intervening reconstruction. A scoring system was used to assess optimal radiotherapy planning using four parameters: breadth of chest wall coverage, treatment of the ipsilateral internal mammary chain, minimization of lung, and avoidance of heart. An "optimal" plan achieved all objectives or a minor 0.5 point deduction; "moderately" compromised treatment plans had 1.0 or 1.5 point deductions; and "major" compromised plans had > or =2.0 point deductions. RESULTS: Of the 112 PMRT plans scored after reconstruction, 52% had compromises compared with 7% of matched controls (p < 0.0001). Of the compromised plans after reconstruction, 33% were considered to be moderately compromised plans and 19% were major compromised treatment plans. Optimal chest wall coverage, treatment of the ipsilateral internal mammary chain, lung minimization, and heart avoidance was achieved in 79%, 45%, 84%, and 84% of the plans in the group undergoing immediate reconstruction, compared respectively with 100%, 93%, 97%, and 92% of the plans in the control group (p < 0.0001, p < 0.0001, p = 0.0015, and p = 0.1435). In patients with reconstructions, 67% of the "major" compromised radiotherapy plans were left-sided (p < 0.16). CONCLUSIONS: Radiation treatment planning after immediate breast reconstruction was compromised in more than half of the patients (52%), with the largest compromises observed in those with left-sided cancers. For patients with locally advanced breast cancer, the potential for compromised PMRT planning should be considered when deciding between immediate and delayed reconstruction.     

A placebo-controlled, randomized withdrawal study of sertraline for major depressive disorder in Japan

The objective of this double-blind, placebo-controlled, multicentre randomized withdrawal study was to evaluate the efficacy and tolerability of sertraline for 16 weeks in treating Japanese patients with major depressive disorder (MDD) who had achieved a response to 8 weeks of sertraline treatment. Patients (n=361) were initially treated with 8 weeks of open-label sertraline treatment followed by 16 weeks of double-blind treatment with either sertraline (50-100 mg/day) or placebo. Responders during the open-label phase were eligible to be entered into the double-blind phase. A total of 235 patients (65.1%) were entered to the double-blind phase and randomly assigned to receive sertraline (n=117) or placebo (n=118). A significantly (P=0.016) lower relapse rate was found for sertraline (8.5%) compared to placebo (19.5%) during the double-blind phase. Examination of time-to-relapse showed that the relapse free rate curve was significantly higher for sertraline (log-rank test, P=0.026) than placebo. Mean changes from beginning to end of the double-blind phase on measure of depressive symptoms, quality of life and global improvement also significantly favoured sertraline over placebo. Sertraline was well-tolerated, with similar adverse events as found in previous studies. These results confirm the efficacy of sertraline in preventing the relapse of MDD in Japanese patients.     

The dentist and prepaid capitated systems

Dentistry's involvement in HMOs and alternative delivery systems has increased dramatically in recent years. Because funding available for dental care is interdependent of general medical expenditures, ways must be found to utilize resources most appropriately. Dentists involved in the new reimbursement programs must understand the risks they are taking.