No abstract

Diabetes increases gingival collagenase activity, an effect that may be mediated by endogenous tissue changes and exacerbated by an overgrowth of Gram‐negative organisms in the gingival crevice (see Ramamurthy & Golub 1983, McNamara et al. 1982). In an attempt to reverse this collagenolytic abnormality, we administered an appropriate antibiotic, minocycline (a semisynthetic tetracycline), to diabetic rats and humans. Adult male conventional or germfree rats were made diabetic with streptozotocin, and half of these animals were administered minocycline (20 mg per day) by tube feeding for 3–4 weeks prior to sacrifice. The buccal gingiva, entire skins, and mandibles were dissected and tested for collagenolytic enzyme activity, collagen content, and alveolar bone loss, espectively. In a preliminary study, minocycline (200 mg per day) was administered for 7 days to an insulin‐dependent diabetic adolescent human and an adult non‐diabetic human; the twin brother of the diabetic was treated with penicillin. Gingival fluid collagenase activity was measured (using [3H‐methyl] collagen as substrate in a new microassay) in 8 periodontal pockets in each subject before and after antibiotic therapy. Examination of collagenase digestion products by SDS‐polyacrylamide gel electrophoresis and fluorography was also carried out. In rats, minocycline treatment: (1) suppressed the abnormally elevated collagenolytic enzyme activity in gingiva of diabetic rats, even under germfree conditions; (2) inhibited PMN leukocyte collagenase activity in vitro, an effect that was reversed by the addition of calcium ions (penicillin‐streptomycin had no effect on the activity of this enzyme); and (3) retarded the abnormal loss of skin collagen and alveolar bone in diabetic rats. In a preliminary study on humans, minocycline therapy reduced the collagenase activity of gingival crevicular fluid, an effect not produced by penicillin. Our data suggests that (1) tetracycline therapy inhibits tissue collagenolytic enzyme activity by a mechanism al least in part unrelated to its antibacterial efficacy, and (2) this mechanism may provide a new therapeutic approach for suppressing excessive collagen resorption which occurs during periodontal disease and which can occur during other pathologic conditions.

BACKGROUNDPatients older than 55 years of age with acute myelogenous leukemia (AML) are less likely to achieve complete remission and more likely to experience toxicity with conventional induction chemotherapy than younger patients. Azacitidine administered in the outpatient setting is well tolerated and can induce complete hematological remission in patients with myelodysplastic syndromes (MDS). At higher doses, azacitidine has activity in AML.METHODSTwenty patients were retrospectively identified who had been treated with azacitidine with bone marrow blast counts between 21 and 38%. Patients with blast counts up to 29% were initially treated as MDS, but by WHO now meet criteria for AML. Patients with blast counts over 29% were treated with azacitidine after being deemed poor candidates for induction chemotherapy. Azacitidine 75 mg/m2/day was administered subcutaneously for 7 days every 4 weeks, which was defined as 1 cycle.RESULTSThe overall response rate was 60% (12/20): complete response (CR; n = 4; 20%); partial response (PR; n = 5; 25%); hematologic improvement (HI; n = 3; 15%). The median survival of responders was 15+ months compared with 2.5 months for nonresponders (P = .009). During therapy, responders had an Eastern Cooperative Oncology Group (ECOG) performance status of 1 or 0. The most common toxic event was infection (n = 8). Four patients were hospitalized during the first cycle of treatment.CONCLUSIONSAzacitidine administered in the outpatient setting can induce remission in AML. The therapy is well tolerated and might be an alternative for patients unlikely to tolerate standard induction chemotherapy. Cancer 2006. © 2006 American Cancer Society.

Oral health care professionals, especially periodontists, must recognize that gingival enlargement may represent an initial manifestation of an underlying systemic disease. Acute myelogenous leukemia is a hematological disorder with a predilection for gingival involvement.

Introduction Atypical hemolytic uremic syndrome (aHUS) is a prototypic thrombotic microangiopathy attributable to complement dysregulation. In the absence of complement inhibition, progressive clinical deterioration occurs. We postulated that a biopsy of normal skin could corroborate the diagnosis of aHUS via the demonstration of vascular deposits of C5b-9. Materials and methods Biopsies of normal skin from 22 patients with and without aHUS were processed for routine light microscopy as well as immunofluorescent studies. An assessment was made for vascular C5b-9 deposition immunohistochemically and by immunofluorescence. The biopsies were obtained primarily from the forearm and or deltoid. Results Patients with classic features of atypical HUS showed insidious microvascular changes including loose luminal platelet thrombi except in two patients in whom a striking thrombogenic vasculopathy was apparent in biopsied digital ulcers. Extensive microvascular deposits of the membrane attack complex (MAC)/ C5b-9 were identified excluding one patient in whom eculizumab was initiated prior to biopsy. In 5 of the 7 patients where follow-up was available, the patients exhibited an excellent treatment response to eculizumab. Patients without diagnostic clinical features of atypical HUS failed to show significant vascular deposits of complement except two patients with TTP including one in whom a Factor H mutation was identified. Conclusion In a clinical setting where aHUS is an important diagnostic consideration, extensive microvascular deposition of C5b-9 supports the diagnosis of either aHUS or a subset of TTP patients with concomitant complement dysregulation; significant vascular C5b-9 deposition predicts clinical responsiveness to eculizumab.