Topical treatment with imiquimod may induce regression of facial keratoacanthoma

Keratoacanthoma (KA) is a rapidly growing tumour histologically resembling squamous cell carcinoma. Although it may regress spontaneously, KA is routinely treated by excision or radiation therapy. Here we report on the successful therapeutic use of imiquimod for the treatment of KA. Four patients with a one to six week history of facial KA were treated with imiquimod cream 5 % every second day for four to 12 weeks. In each patient, KA fully regressed under topical treatment with imiquimod. In three of the patients, KA had disappeared within four to six weeks. In two patients, disappearance was confirmed histologically. No recurrence occurred during a four- to six-month follow-up-period. Our observations indicate that topical immunostimulation with imiquimod may induce or promote immune defence mechanisms leading to KA regression. Imiquimod might therefore prove to be an effective non-invasive treatment modality for KA that warrants more extensive evaluation by clinical studies.     

A possible influence of gingival dimensions on attachment loss and gingival recession following placement of artificial crowns

The aim of the present study was to determine the influence of gingival dimensions on the development of gingival recession following placement of artificial crowns. The study population consisted of 11 periodontally healthy patients in whom 44 maxillary anterior teeth and/or premolars had to be crowned. A total of 36 teeth (82%) had, after crown placement, a mean intracrevicular crown margin of 0.57 +/- 0.47 mm. Thirty-nine teeth without restorations served as controls. Immediately after incorporation, as well as after 3, 6, 9, and 12 months, periodontal examinations were carried out. Gingival thickness was determined sonometrically and averaged 1.25 +/- 0.40 mm. Mean periodontal probing depth was 1.80 +/- 0.54 mm. Twelve months later, crowned teeth had experienced a mean attachment loss of 0.17 +/- 0.99 mm as compared to an attachment gain of 0.18 +/- 0.46 mm at control teeth. At test teeth, the gingival margin had receded a mean of 0.43 +/- 0.74 mm. In multivariate analyses considering the correlated structure of the data employing generalized estimating equation methods, crown placement was identified as a major factor for attachment loss and development of gingival recession. In addition, a shallow probing depth and narrow band of gingiva negatively influenced the level of periodontal attachment. The present results point to the importance of a more detailed periodontal diagnosis of the dentogingival region before placement of artificial crowns.     

Surface characteristics of implants influence their bone integration after simultaneous placement of implant and GBR membrane

The purpose of this study was to evaluate the influence of titanium surface characteristics on bone integration of implants, and to describe the pattern of peri-implant tissue healing after simultaneous implant placement and guided bone regeneration. In four healthy mongrel dogs mandibular premolars were extracted. Two weeks following full mouth prophylaxis and 4 months after extractions, simultaneous membrane and implant surgeries were performed. Efforts were made to produce bony defects with dimensions of 7 x 7 x 7 mm. Into these, 24 standard ITI implants (diameter = 4.1 mm; length = 8 mm) with either a titanium plasma-sprayed (TPS) or a machined surface (MS) were placed. Although implants were inserted 4 mm into cancellous bone, difficulties in achieving optimal primary stability were encountered. All dogs were maintained on a soft diet. Chlorhexidine rinses were performed three times a week. Full mouth prophylaxis was performed every 2 weeks. In the case of membrane exposure, the membranes were removed prematurely (4-6 or 14-15 weeks after surgery). Two dogs were sacrificed at 16 weeks and two at 24 weeks after surgery. Nondecalcified histologic sections were processed and histometric analyses were carried out. When membranes were removed after 4-6 weeks, a vertical bone growth (VB) of 45-61% of the original defect was noted. After membrane removal at 14-15 weeks, similar VB was observed. However, if membranes were left in situ for 24 weeks, VB was between 79% and 96%. In this group of sites, the VB was 66% at 16 weeks and 86% at 24 weeks. Osseointegration in the regenerated bone area ranged from 12% to 32% for the TPS and from 0.0% to 3.6% for the MS implants at 16 and 24 weeks combined. Osseointegration in the pristine host bone area ranged from 16% to 35% for the TPS and from 0.0% to 11% for the MS sites at 16 and 24 weeks. In conclusion, the fraction of implant-bone integration was much higher in the pristine bone compared to that in the regenerated bone. TPS surfaces positively influenced the fraction of osseointegration in comparison to MS surfaces for both regenerated and pristine bone. Furthermore, early membrane removal negatively affected the fraction of bone defect fill.     

Effect of soluble receptors to interleukin-1 and tumor necrosis factor alpha on experimentally induced root resorption in rats

OBJECTIVE: In this study, the role of the inflammatory cytokines interleukin-1 (IL-1) and tumor necrosis factor alpha (TNFalpha) in the course of mechanically induced root resorption was investigated. METHODS: Mechanical induction of root resorption was performed on the upper left first molars in 18 male Wistar rats according to the method of Nakane and Kameyama. Starting on day minus 1, six animals received daily intraperitoneal injections of 2 ml of 1 micro g/ml soluble receptors to IL-1 (sIL-1RII) and another six animals were administered the same dose of soluble receptors to TNFalpha (sTNFalpha-RI). Six animals served as a control. On d 7 the left maxillae were prepared for histological and morphometric analysis of the extent of the root resorption that had developed. RESULTS: The qualitative and quantitative results demonstrated that in both receptor groups the amount of root resorption was significantly reduced. Especially following systemic application of sTNFalpha-RI, root resorption was nearly completely prevented. CONCLUSIONS: Our results indicate that IL-1 and more particularly TNFalpha are important for the induction and the further process of mechanically induced root resorption in the rat.     

Early improvement under mirtazapine and paroxetine predicts later stable response and remission with high sensitivity in patients with major depression

OBJECTIVE: Current clinical knowledge holds that antidepressants have a delayed onset of efficacy. However, the delayed onset hypothesis has been questioned recently by survival analytical approaches. We aimed to test whether early improvement under antidepressant treatment is a clinically useful predictor of later stable response and remission. METHOD: We analyzed data from a randomized double-blind controlled trial with mirtazapine and paroxetine in patients with major depression (DSM-IV). Improvement was defined as a 17-item Hamilton Rating Scale for Depression (HAM-D-17) score reduction of > or = 20%. Stable response was defined as > or = 50% HAM-D-17 score reduction at week 4 and week 6, and stable remission as a HAM-D-17 score of < or = 7 at week 4 and week 6. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. RESULTS: Improvement occurred in a majority of the analyzed patients within 2 weeks (mirtazapine: 72.7% of 109 patients; paroxetine: 64.9% of 103 patients). Early improvement was a highly sensitive predictor of later stable response or stable remission for both drugs. NPV approached maximum values as early as week 2 for mirtazapine and week 3 for paroxetine. After 2 weeks of treatment with mirtazapine and 3 weeks with paroxetine, almost none of the patients who had not yet improved became a stable responder or stable remitter in the later course. CONCLUSION: Our results strongly suggest that early improvement predicts later stable response with high sensitivity. These empirically derived data question the delayed onset hypothesis for both antidepressants tested and provide important clinical clues for an individually tailored antidepressant treatment.     

Subchronic inhalation neurotoxicity studies of ethyl acetate in rats

Rats were exposed to 0, 350, 750 or 1500 ppm of ethyl acetate by inhalation for 6 h per day, 5 days per week for 13 weeks. Functional observational battery (FOB) and motor activity tests occurred on non-exposure days during weeks 4, 8 and 13, after which tissues were microscopically examined for neuropathology. A subset of rats was monitored during a 4-week recovery period. Exposure to 750 and 1500 ppm, diminished behavioral responses to unexpected auditory stimuli during the exposure session and appeared to be an acute sedative effect. There were no signs of acute intoxication 30 min after exposure sessions ended. Rats exposed to 750 and 1500 ppm had reduced body weight, body weight gain, feed consumption, and feed efficiency, which fully or partially recovered within 4 weeks. Reductions in body weight gain and feed efficiency were observed in male rats exposed to 350 ppm. The principal behavioral effect of subchronic exposure was reduced motor activity in the 1500 ppm females, an effect that was not present after the 4-week recovery period. All other FOB and motor activity parameters were unaffected, and no pathology was observed in nervous system tissues. Operant sessions were conducted in another set of male rats preconditioned to a stable operant baseline under a multiple fixed ratio-fixed interval (FR-FI) schedule of food reinforcement. FR response rate, FR post-reinforcement pause duration, and the pattern of FI responding were not affected during or after the exposure series. In contrast, within-group FI rate for the treatment groups increased over time whereas those of the controls decreased. A historical control group, however, also showed a similar pattern of increase, indicating that these changes did not clearly represent a treatment-related effect. Results from these studies indicate a LOEL of 350 ppm for systemic toxicity based on the decreased body weight gain in male rats, and a LOEL of 1500 ppm for neurotoxicity based on the transient reduction in motor activity in female rats. In conclusion, there was no evidence that subchronic exposure up to 1500 ppm ethyl acetate produced any enduring neurotoxic effects in rats.     

Hemostatic complications in bone marrow transplantation: a retrospective analysis of 447 patients

BACKGROUND: Hemostatic complications are not uncommon after bone marrow transplantation (BMT). However, little is known about the frequency, localization, determinants, and outcome of hemostatic events in autologous and allogeneic BMT. METHODS: Four hundred forty-seven patients (364 allogeneic, 83 autologous transplants) were evaluated retrospectively for the presence of hemostatic complications (bleeding, thrombosis, hepatic veno-occlusive disease [VOD], microangiopathic hemolytic anemia) from the start of conditioning therapy until June 2000. RESULTS: A total of 83.2% of the patients presented with at least one hemostatic complication during the investigational period. Most bleeding episodes occurred within the first 4 weeks after transplantation and were relatively mild. However, 27.1% of the patients hemorrhaged severely, generally doubling the overall mortality of the BMT recipients. Fatal gastrointestinal or intracerebral hemorrhages contributed to 1.1% of the events. Bleeding was strongly associated with prolonged thrombocytopenia and graft-versus-host disease (GVHD). Hemorrhagic cystitis may additionally have been triggered by the preceding conditioning regimens containing cyclophosphamide. Thromboembolic events occurred most frequently in allogeneic transplant recipients, for whom the incidence was 14.6%. Chronic GVHD and treatment with steroids were the major determining factors. The incidence of hepatic VOD in 4.7% of the allogeneic transplant recipients was associated with a high fatality rate. Busulfan conditioning increased the VOD risk 2.6-fold. Moderate or severe microangiopathic hemolytic anemia was associated with GVHD and occurred in 14.6% of the allogeneic transplant recipients, leading to an increased overall mortality. CONCLUSION: Hemostatic disturbances, commonly found in the course of transplantation, are associated with a high transplantation risk and closely related to thrombocytopenia and immunologic complications.