Randomized trial of daily versus weekly administration of 2-chlorodeoxyadenosine in patients with hairy cell leukemia: a multicenter phase III trial (SAKK 32/98)

Daily administration of 2-chlorodeoxyadenosine (Cladribine, CDA) is a standard treatment for hairy cell leukemia, but may cause severe neutropenia and neutropenic fever. This trial compared toxicity and efficacy of weekly versus daily CDA administration. One hundred patients were randomized to receive standard (CDA 0.14 mg/kg/day day 1-5 [Arm A]) or experimental treatment (CDA 0.14 mg/kg/day once weekly for 5 weeks [Arm B]). The primary endpoint was average leukocyte count within 6 weeks from randomization. Secondary endpoints included response rates, other acute hematotoxicity, acute infection rate, hospital admission, remission duration, event-free, and overall survival. There was no significant difference in average leukocyte count. Response rate (complete + partial remission) at week 10 was 78% (95% confidence interval (CI) 64-88%) in Arm A and 68% (95% CI 54-80%) in Arm B (p = 0.13). Best response rates during follow-up were identical (86%) in both arms. No significant difference was found in the rate of grade 3+4 leukocytopenia (94%vs. 84%), grade 3+4 neutropenia (90%vs. 80%), acute infection (44%vs. 40%), hospitalization (38%vs. 34%), and erythrocyte support (22%vs. 30%) within 10 weeks. Overall, these findings indicate that there are no apparent advantages in toxicity and efficacy by giving CDA weekly rather than daily.

Outcome evaluation of early placed maxillary anterior single-tooth implants using objective esthetic criteria: a cross-sectional, retrospective study in 45 patients with a 2- to 4-year follow-up using pink and white esthetic scores

BACKGROUND: To validate the concept of early implant placement for use in the esthetically sensitive anterior maxilla, clinical trials should ideally include objective esthetic criteria when assessing outcome parameters. METHODS: In this cross-sectional, retrospective 2- to 4-year study involving 45 patients treated with maxillary anterior single-tooth implants according to the concept of early implant placement, a novel comprehensive index, comprising pink esthetic score and white esthetic score (PES/WES; the highest possible combined score is 20), was applied for the objective esthetic outcome assessment of anterior single-tooth implants. RESULTS: All 45 anterior maxillary single-tooth implants fulfilled strict success criteria for dental implants with regard to osseointegration, including the absence of peri-implant radiolucency, implant mobility, suppuration, and pain. The mean total PES/WES was 14.7 +/- 1.18 (range: 11 to 18). The mean total PES of 7.8 +/- 0.88 (range: 6 to 9) documents favorable overall peri-implant soft tissue conditions. The two PES variables facial mucosa curvature (1.9 +/- 0.29) and facial mucosa level (1.8 +/- 0.42) had the highest mean values, whereas the combination variable root convexity/soft tissue color and texture (1.2 +/- 0.53) proved to be the most difficult to fully satisfy. Mean scores were 1.6 +/- 0.5 for the mesial papilla and 1.3 +/- 0.5 for the distal papilla. A mean value of 6.9 +/- 1.47 (range: 4 to 10) was calculated for WES. CONCLUSIONS: This study demonstrated that anterior maxillary single-tooth replacement, according to the concept of early implant placement, is a successful and predictable treatment modality, in general, and from an esthetic point of view, in particular. The suitability of the PES/WES index for the objective outcome assessment of the esthetic dimension of anterior single-tooth implants was confirmed. However, prospective clinical trials are needed to further validate and refine this index.

Liraglutide once a day versus exenatide twice a day for type 2 diabetes: a 26-week randomised, parallel-group, multinational, open-label trial (LEAD-6)

BACKGROUND: Unlike most antihyperglycaemic drugs, glucagon-like peptide-1 (GLP-1) receptor agonists have a glucose-dependent action and promote weight loss. We compared the efficacy and safety of liraglutide, a human GLP-1 analogue, with exenatide, an exendin-based GLP-1 receptor agonist. METHODS: Adults with inadequately controlled type 2 diabetes on maximally tolerated doses of metformin, sulphonylurea, or both, were stratified by previous oral antidiabetic therapy and randomly assigned to receive additional liraglutide 1.8 mg once a day (n=233) or exenatide 10 microg twice a day (n=231) in a 26-week open-label, parallel-group, multinational (15 countries) study. The primary outcome was change in glycosylated haemoglobin (HbA(1c)). Efficacy analyses were by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00518882. FINDINGS: Mean baseline HbA(1c) for the study population was 8.2%. Liraglutide reduced mean HbA(1c) significantly more than did exenatide (-1.12% [SE 0.08] vs -0.79% [0.08]; estimated treatment difference -0.33; 95% CI -0.47 to -0.18; p<0.0001) and more patients achieved a HbA(1c) value of less than 7% (54%vs 43%, respectively; odds ratio 2.02; 95% CI 1.31 to 3.11; p=0.0015). Liraglutide reduced mean fasting plasma glucose more than did exenatide (-1.61 mmol/L [SE 0.20] vs -0.60 mmol/L [0.20]; estimated treatment difference -1.01 mmol/L; 95% CI -1.37 to -0.65; p<0.0001) but postprandial glucose control was less effective after breakfast and dinner. Both drugs promoted similar weight losses (liraglutide -3.24 kg vs exenatide -2.87 kg). Both drugs were well tolerated, but nausea was less persistent (estimated treatment rate ratio 0.448, p<0.0001) and minor hypoglycaemia less frequent with liraglutide than with exenatide (1.93 vs 2.60 events per patient per year; rate ratio 0.55; 95% CI 0.34 to 0.88; p=0.0131; 25.5%vs 33.6% had minor hypoglycaemia). Two patients taking both exenatide and a sulphonylurea had a major hypoglycaemic episode. INTERPRETATION: Liraglutide once a day provided significantly greater improvements in glycaemic control than did exenatide twice a day, and was generally better tolerated. The results suggest that liraglutide might be a treatment option for type 2 diabetes, especially when weight loss and risk of hypoglycaemia are major considerations.

C-3 Alkyl /Arylalkyl-2,3-dideoxy hex-2-enopyranosides as Antitubercular Agents: Synthesis, Biological Evaluation and QSAR Study

A series of C-3 alkyl and arylalky 2,3-dideoxy hex-2-enopyranoside derivatives were synthesized by Morita-Baylis-Hillman reaction using enulosides 4, 5 and 6 and various aliphatic and aromatic aldehydes. The compounds were evaluated in vitro for the complete inhibition of growth of Mycobacterium tuberculosis H37Rv. They exhibited moderate to good activity in the range of 25-1.56 µg/mL. Among these, 4d, 4h, 5c and 4hr showed activity at minimum inhibitory concentrations, 3.12, 6.25, 1.56 and 1.56µg/mL, respectively. These compounds were safe against cytotoxicity in VERO cell line and mouse macrophage cell line J 744A.1. A QSAR analysis by CP-MLR with alignment-free 3D-descriptors indicated the relevance of structure space comparable to the minimum energy conformation (from conformational analysis) of 5c to the activity. The study indicates that the compounds attaining conformational space 5c and reflecting some symmetry, minimum eccentricity and closely placed geometric and electronegativity centers therein are favorable for activity.

Survival of bonded lingual retainers with chemical or photo polymerization over a 2-year period: a single-center, randomized controlled clinical trial

INTRODUCTION The objective of this trial was to compare the survival rates of mandibular lingual retainers bonded with either chemically cured or light-cured adhesive after orthodontic treatment. METHODS Patients having undergone orthodontic treatment at a private orthodontic office were randomly allocated to fixed retainers placed with chemically cured composite or light-cured composite. Eligibility criteria included no active caries, restorations, or fractures on the mandibular anterior teeth, and adequate oral hygiene. The main outcome was any type of first-time lingual retainer breakage; pattern of failure (adapted adhesive remnant index scores) was a secondary outcome. Randomization was accomplished with random permuted blocks of 20 patients with allocation concealed in sequentially numbered, opaque, sealed envelopes. Blinding was applicable for outcome assessment only. Patients were reviewed at 1, 3, and 6 months and then every 6 months after placement of the retainer until completion of the study. Data were analyzed using survival analysis including Cox regression; sensitivity analysis was carried out after data imputation for subjects lost to follow-up. RESULTS Two hundred twenty patients (median age, 16 years; interquartile range, 2; range, 12-47 years) were randomized in a 1:1 ratio to either chemical or light curing. Baseline characteristics were similar between groups, the median follow-up period was 2.19 years (range, 0.003-3.64 years), and 16 patients were lost to follow-up. At a minimum follow-up of 2 years, 47 of 110 (42.7%) and 55 of 110 (50.0%) retainers had some type of failure with chemically cured and light-cured adhesive, respectively (log-rank test, P = 0.35). Data were analyzed on an intention-to-treat basis, and the hazard ratio (HR) was 1.15 (95% confidence interval [CI], 0.88-1.70; P = 0.47). There was weak evidence that age is a significant predictor for lingual retainer failures (HR, 0.96; 95% CI, 0.93-1.00; P = 0.08). Adhesive remnant index scoring was possible for only 66 of the 102 (64.7%) failures and did not differ between composites (Fisher exact test, P = 0.16). No serious harm was observed other than gingivitis associated with plaque accumulation. CONCLUSIONS The results of this study indicated no evidence that survival of mandibular lingual retainers differs between chemically and light-cured adhesives. The overall failure rate was 46.4%; however, this included any type of failure, which may have exaggerated the overall failure rate.

Der Austritt aus der Synagogengemeinde : das Gesetz u. dessen Berathung im Hause d. Abgeordneten in 1., 2. u. 3. Lesung, nach d. stenogr. Berichten d. Abgeordnetenhauses zsgest. u. mit e. Vorw. vers.

von S. Meyer

Ms. hebr. oct. 88 - Mivḥar ha-maʼamarim

Vorbesitzer: Eljāqīm Carmoly; Abraham Merzbacher

Ms. Barth. 88 - Juristische Sammelhandschrift

Vorbesitzer: Johannes Usingen; Bartholomaeusstift Frankfurt am Main

Creating Useful Products From Connecticut's 2000 LIDAR Data Set JHR 08-314 Project 07-2

The State of Connecticut owns a LIght Detection and Ranging (LIDAR) data set that was collected in 2000 as part of the State’s periodic aerial reconnaissance missions. Although collected eight years ago, these data are just now becoming ready to be made available to the public. These data constitute a massive “point cloud”, being a long list of east-north-up triplets in the State Plane Coordinate System Zone 0600 (SPCS83 0600), orthometric heights (NAVD 88) in US Survey feet. Unfortunately, point clouds have no structure or organization, and consequently they are not as useful as Triangulated Irregular Networks (TINs), digital elevation models (DEMs), contour maps, slope and aspect layers, curvature layers, among others. The goal of this project was to provide the computational infrastructure to create a first cut of these products and to serve them to the public via the World Wide Web. The products are available at http://clear.uconn.edu/data/ct_lidar/index.htm.

Ms. Praed. 88 - [Sammelband in 5 Teilen: Konvolut aus Handschriften und Inkunabeln]

Vorbesitzer: Dominikanerkloster Frankfurt am Main

Ms. lat. oct. 113 (mit Ausst. 88) - Rituale exorcismorum

Vorbesitzer: Oswaldus, Pleban in Ostheim (Vorbesitzer?), Karmeliterkloster Frankfurt am Main

Dem verehrten Freunde als kleine Erinnerung an die Bewohnerinnen Anna und Helene Stahr, u. an den theuren Meister Franz Liszt, der alljährlich in dem Häuschen Weimar Schwanseestr. 5 ein und aus ging zum 14ten Oct. 88.

Signatur des Originals: S 36/F10915

Ms.Ff.F.Stoltze 3. 88 - Brief von Wilhelm August Gaertner an Friedrich Stoltze

Bittbrief, Persönliche Nachrichten, Johann Albrecht Vogtherr, Seydewitz, Prüning, Leopold Sonnemann, Carl Holthof, Oppel, Miquel