Treatment-free remission following frontline nilotinib in patients with chronic myeloid leukemia in chronic phase: results from the ENESTfreedom study.

The single-arm, phase 2 ENESTfreedom trial assessed the potential for treatment-free remission (TFR; i.e., the ability to maintain a molecular response after stopping therapy) following frontline nilotinib treatment. Patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase with MR4.5 (BCR-ABL1⩽0.0032% on the International Scale (BCR-ABL1IS)) and ⩾2 years of frontline nilotinib therapy were enrolled. Patients with sustained deep molecular response during the 1-year nilotinib consolidation phase were eligible to stop treatment and enter the TFR phase. Patients with loss of major molecular response (MMR; BCR-ABL1IS⩽0.1%) during the TFR phase reinitiated nilotinib. In total, 215 patients entered the consolidation phase, of whom 190 entered the TFR phase. The median duration of nilotinib before stopping treatment was 43.5 months. At 48 weeks after stopping nilotinib, 98 patients (51.6%; 95% confidence interval, 44.2-58.9%) remained in MMR or better (primary end point). Of the 86 patients who restarted nilotinib in the treatment reinitiation phase after loss of MMR, 98.8% and 88.4%, respectively, regained MMR and MR4.5 by the data cutoff date. Consistent with prior reports of imatinib-treated patients, musculoskeletal pain-related events were reported in 24.7% of patients in the TFR phase (consolidation phase, 16.3%).

Prevalence of Oral Lesions in the Elderly.

OBJECTIVE: Geriatric dentistry refers to dealing with oral diseases including prevention and treatment in old individuals. The aim of this investigation was to examine the types and frequency of oral lesions in the elderly. SUBJECTS AND METHODS: The study involved 75 elderly persons. The clinical diagnosis was established by correlating the aetiological factor associated with the lesion and by systematic examination of the oral mucosa and classifying those alterations according to the epidemiological guidelines for the diagnosis of oral mucosal diseases. During the clinical examination, the following elements were analysed: features of the lesion, anatomical location, extension, aetiological factors or related factors, dental status, alcohol, tobacco, trauma, use of prosthesis and if such were well adapted. RESULTS: Sixty lesions were diagnosed in 75 patients. These were classified according to clinical, histopathological and microbiological diagnosis and were distributed into 15 different clinical entities. The more prevalent pathologies were inflammatory, reactive and associated with long-term use of prostheses or ill-adapted prostheses, since 67% of the patients with lesions were using prostheses. Of the lesions related to prosthesis use, denture stomatitis was the most common one, representing 20 cases (33.3%). The second most frequent lesion was erythematous candidiasis (10%). The other most frequent lesions in this study were lingua plicata, xerostomia and pseudomembranous candidiasis. CONCLUSION: Oral and perioral tissues undergo different functional and structural changes with ageing. The role of the dentist and stomatologist includes the management of systemic, nutritional and pharmacological oral manifestations in order to establish an early diagnosis and subsequent accurate treatment.

[Prosthetic rehabilitation in patient with forced class III malocclusion].

The paper presents clinical case of 63 years old edentulous patient with slight class III malocclusion. For 15 years he was using inadequately fabricated dentures causing forced severe class III malocclusion. Forced progeny was corrected by newly fabricated dentures which restored normal orofacial function and facial harmony.

[Effect of calcium hydroxide based desensitizing agent on cast crown retention].

A layer of desensitizing agent for prepared teeth was applied to tooth stump prior to the final cementation of cast crowns in order to alleviate postoperative sensibility. The aim of the study was to establish under in vitro conditions whether the application of the suspension of calcium hydroxide (Kaviner) on prepared teeth decreased the cast crown bonding strength. 40 intact human premolars were extracted for orthodontic reasons and prepared by high capacity machine using water supply cooling. Experimental crowns were made by a standard procedure using NiCrMo alloy and cemented by zinc phosphate or glass ionomer luting cements (20 in each group). Bond strength between prepared teeth and crowns was mechanically tested by using electronic dynamometer, at first without suspension of calcium hydroxide and then after its application. The results obtained pointed to decrease of bonding strength with both used luting cements: decrease of retention force with zinc phosphate cement was equal to 1.9% and with glass ionomer cement - 4.2%. However, the retention forces values obtained after the application of Kaviner for both dental cements observed were still clinically acceptable.

[Maxillary osteonecrosis caused by toxic effect of zinc-oxide-eugenol paste].

Zinc-oxide powder mixed with eugenol or cariofillorum oil and sterilized cotton is frequently used in dental practice as surgical bandage for eliminating or dry socket. Osteonecrosis of alveolar bone caused by free eugenol is rare but possible complication. The aim of this paper is to present a patient with maxillary osteonecrosis complicated with maxillary sinusitis caused by a surgical paste of zinc-oxide. A 47-year-old female patient was admitted to our department after unsuccessful treatment of dry socket with a paste of zinc-oxide. Intense use of zinc-oxide paste as bandage over the extraction sockets caused two separately osteonecrosis of maxillary alveolar bone. Surgical resection of necrotic bone, extraction of adjacent teeth and revision surgery of maxillary sinus was treatment of choice. Postoperative course was uneventful and 6 months postoperatively there weren't present further signs of maxillary necrosis. In preparation of a paste of zinc-oxide as surgical bandage it is necessary that all the powder be filled up with intense mixing with liquid. In present case osteonecrosis was caused by free eugenol in surgical zinc-oxide bandage as well as due to the long term and frequently used of zinc-oxide. In resistant dry sockets we recommended combined method of treatment and not only the use of zinc-oxide paste especially if there was no analgesic and therapeutic effects.

[The significance of the size and type of surface of prepared teeth for retention of permanent dentures fixed with zinc-phosphate cement]. / Znachenie razmera i kharaktera poverkhnosti preparirovannykh zubov dlia retentsii nes"emnykh protezov, zafiksirovannykh tsink-fosfatnym tsementom.

The purpose of this paper was to establish, in vitro, the impact of different sizes and prepared teeth roughness on the adhesion strength with cast crowns. Twenty human intact premolars were used in the experiment. They were prepared and divided into two groups depending on the fineness of diamond prepared instrumentation. Sizes of prepared teeth were calculated mathematically, while the dentine roughness was measured by a profile meter. The cast crowns were made by a standard method for each group. The crowns were then cemented with a zinc phosphate cement. After seven days, testing of prepared teeth and cast crowns bonding strength was carried out mechanically in an electronic dynamometer. On the basis of the obtained results the relationship between the size and the accomplished roughness with the obtained values of the retention forces is observed. At the constant convergence angle of the stamp the retention is proportional to the stamp size and the roughness profile.

Perinatal changes in choroidal 15-hydroxyprostaglandin dehydrogenase: implications for prostaglandin removal from brain.

We have previously shown in the sheep fetus at 0.7 and 0.9 gestation that the choroid plexus, unlike brain parenchyma, catabolizes prostaglandins (PGs). Peculiarly, in the choroid plexus, PGE(2) catabolism persists throughout the neonatal period to abate in the adult, while PGF(2alpha) catabolism abates shortly after birth. To explain this differential behavior and elucidate the function of catabolic enzymes, we examined the cellular location and activity of the rate-limiting enzyme for PGE(2) and PGF(2alpha) catabolism, 15-hydroxyprostaglandin dehydrogenase (15-PGDH). Immunofluorescence histochemistry and immunogold electronmicroscopy revealed abundant 15-PGDH expression in the epithelial cytosol close to the brush-border membrane at 0.7 and 0.9 gestation. In contrast, at 5 and 15 days postnatal, 15-PGDH was found throughout the cytosol of stromal fibroblasts. No staining was observed at either location in pregnant adults. PGF(2alpha) catabolism was minimal in the total homogenate and 100000xg supernatant of the fetal choroid plexus at 0.7 and 0.9 gestation, while PGE(2) catabolism was evident at 0.7 gestation only. In contrast, both PGs were catabolized in minced specimens at either age. In conclusion, our study shows immunoreactive 15-PGDH in the choroid plexus from fetal and neonatal, but not pregnant adult, sheep. Results suggest that PGE(2) catabolism is not as critically dependent as that of PGF(2alpha) on tissue integrity and 15-PGDH location. Given the key role being assigned to the choroid plexus in PG removal from brain, we speculate that persistence of PGE(2) catabolism into the early postnatal period protects against central respiratory depression caused by the compound during this susceptible stage of development.

Differential uptake and catabolism of prostaglandin (PG)E(2) versus PGF(2alpha) in the sheep choroid plexus during development.

The early postnatal decrease in prostaglandin (PG)E(2) levels in cerebrospinal fluid (CSF) likely contributes to the establishment of continuous breathing. To elucidate mechanisms underlying this event, choroid plexuses from lateral (L-CP) and third/fourth (III/IV-CP) ventricles were incubated with [3H]-PGE(2) and label uptake (tissue-to-medium ratio for radioactivity, T/M) and catabolism (%radioactivity associated with metabolites, PGM) were measured. [3H]-PGF(2alpha) was a reference. Uptake of [3H]-PGE(2) was lower than [3H]-PGF(2alpha) in the term fetus (L-CP: 5.9+/-0.5 vs. 9.6+/-0. 9, n=11; III/IV-CP: 2.7+/-0.4 vs. 7.7+/-1.0, n=5) and 17 d lamb (L-CP: 5.3+/-0.8 vs. 11.0+/-1.2, n=7; III/IV-CP: 3.1+/-0.2 vs. 11. 6+/-2.8, n=3 and 4, respectively). This difference was not significant in the pregnant adult. Release of the two compounds was similar and did not change with age. [3H]-PGE(2) uptake was reduced by probenecid (1 mM) and excess PG (60 microM PGE(2) or PGF(2alpha)). Excess PG also reduced catabolism in the fetus, which was extensive for [3H]-PGE(2) and [3H]-PGF(2alpha)60%). In the lamb, catabolism remained high for [3H]-PGE(2) (L-CP: 64+/-4%, n=7; III/IV-CP: 41+/-4%, n=3), but not [3H]-PGF(2alpha) (L-CP: 26+/-4%, n=7; III/IV-CP: 4+/-1%, n=4). In the pregnant adult, catabolism was above background only for [3H]-PGE(2) in the L-CP (26+/-5%, n=11). Unlike the perinatal animal, this catabolism was reduced by probenecid. In conclusion, PGE(2) uptake and catabolism operate independently in the choroid plexus from perinatal sheep. Differences between PGE(2) and PGF(2alpha) are developmentally-regulated for both mechanisms. While neither process explains the postnatal decrease in CSF PGE(2), both may help keep CSF levels low during early postnatal development.

Prostaglandin uptake and catabolism by the choroid plexus during development in sheep.

We have previously reported that prostaglandin(PG) E2 levels in sheep cerebrospinal fluid (CSF) are high prenatally and abate rapidly after birth. This event may contribute to the establishment of continuous breathing. To explain this change, we have examined PG disposal mechanisms in the perinatal and adult (pregnant and non-pregnant animal) sheep brain by measuring the capacity of the isolated choroid plexus to concentrate [3H]PGF2alpha and [3H]PGE2. At 0.9 gestation, [3H]PGF2alpha uptake (expressed as the tissue-to-medium ratio, T/M) attained a steady-state by 15 min and was maintained thereafter (T/M at 60 min, 5.6 +/- 0.6; n = 16). Likewise, [3H]PGE2 was taken up by the tissue, but the actual accumulation was smaller (T/M at 60 min, 2.6 +/- 0.2; n = 8). Thin-layer radiochromatographic analysis of the tissue following incubation with [3H]PGF2alpha showed that 55 +/- 4% (n = 10) of radioactivity migrated as the 15-keto-13,14-dihydro metabolite. [3H]PGF2alpha uptake decreased upon treatment with probenecid (1 mM) (T/M, 2.5 +/- 0.2; n = 10) or after adding unlabelled PGF2alpha to the medium (1-60 microM) (T/M at 60 microM, 1.8 +/- 0.1; n = 13). The yield of labelled metabolite was also lower when using excess PGF2alpha (14% of control at 60 microM; n = 13), while it was not affected by probenecid. Uptake of both PGs did not change through development, from 0.7 gestation to day 18 postnatal, and attained higher values in the pregnant adult. Conversely, PGF2alpha catabolism decreased postnatally and became negligible by adult age. We conclude that during the perinatal period PGs can be removed from CSF by two distinct processes in the choroid plexus, active transport and catabolism. Neither process, however, can account for the birth-related change in CSF PGE2.