CO2 laser vaporization for the treatment of vaginal intraepithelial neoplasia: effectiveness and predictive factors for recurrence.

Objective: To evaluate the outcome of vaginal intraepithelial neoplasia (VaIN) treatment with CO2 laser vaporization in terms of local recurrence and progression to vaginal carcinoma. Additionally, the authors investigated the predictive factors for first recurrence.

Materials And Methods: The medical records of all patients treated for VaIN with CO2 laser vaporization at Sant'Anna Hospital in Turin (1995-2012), were retrospectively reviewed.

[Cervical cancer screening in Italy: quality of colposcopy and treatment. 2010 activity].

Data were collected from organised Italian cervical screening programmes on: a) the correlation between colposcopic findings (according to the 1990 international classification) and histology, and (b) the treatment/management of screen-detected histologically-confirmed cervical intraepithelial neoplasia (CIN). Data routinely registered by organised programmes were obtained as aggregated tables. Of the 26,320 reported colposcopies, 39.

Cervical cancer screening in Italy: quality of colposcopy and treatment. 2009 activity.

We collected data from organised Italian cervical screening programmes on: a) the correlation between colposcopic findings (according to the 1990 international classification) and histology, and (b) the treatment/management of screen-detected histologically-confirmed cervical intraepithelial neoplasia (CIN). Data routinely registered by organised programmes were obtained as aggregated tables. Of the 30,049 reported colposcopies, 40.

Quality of colposcopy and treatment: data from the national survey of Italian organised cervical screening programmes. 2008 activity.

We collected data from organised Italian cervical screening programmes on (a) the correlation between colposcopic findings (according to the 1990 international classification) and histology, and (b) the treatment/management of screen-detected histologically confirmed cervical intraepithelial neoplasia (CIN). Data routinely registered by organised programmes were obtained as aggregated tables. Of the 25,932 reported colposcopies 38.

Quality of colposcopy and treatment--data from the national survey of Italian organised cervical screening programmes: 2006 activity.

We collected from Italian organised cervical screening programmes data on the correlation between colposcopic findings (according to the 1990 international classification) and histology and on the treatment/management of screen-detected histologically confirmed cervical intraepithelial neoplasia (CIN). Data routinely registered by organised programmes were provided as aggregated tables. We obtained data on colpo-histological correlation from 72 programmes.

A practical enantioselective synthesis of odanacatib, a potent Cathepsin K inhibitor, via triflate displacement of an alpha-trifluoromethylbenzyl triflate.

An enantioselective synthesis of the Cathepsin K inhibitor odanacatib (MK-0822) 1 is described. The key step involves the novel stereospecific S(N)2 triflate displacement of a chiral alpha-trifluoromethylbenzyl triflate 9a with (S)-gamma-fluoroleucine ethyl ester 3 to generate the required alpha-trifluoromethylbenzyl amino stereocenter. The triflate displacement is achieved in high yield (95%) and minimal loss of stereochemistry.

Quality of colposcopy and treatment: data from the national survey of Italian organised cervical screening programmes.

We collected from Italian organised cervical screening programmes data (a) on the correlation between colposcopic findings (according to the 1990 international classification) and histology, and (b) on the treatment/management of screen-detected histologically confirmed cervical intraepithelial neoplasia (CIN). Data routinely registered by organised programmes was provided as aggregated tables. We obtained data on colpo-histological correlation from 63 programmes.

Results at recruitment from a randomized controlled trial comparing human papillomavirus testing alone with conventional cytology as the primary cervical cancer screening test.

Background: In the first recruitment phase of a randomized trial of cervical cancer screening methods (New Technologies for Cervical Cancer Screening [NTCC] study), we compared screening with conventional cytology with screening by human papillomavirus (HPV) testing in combination with liquid-based cytology. HPV-positive women were directly referred to colposcopy if aged 35 or older; if younger, they were retested after 1 year.

Methods: In the second recruitment phase of NTCC, we randomly assigned women to conventional cytology (n = 24,661) with referral to colposcopy if cytology indicated atypical squamous cells of undetermined significance or more severe abnormality or to testing for high-risk HPV DNA alone by Hybrid Capture 2 (n = 24,535) with referral to colposcopy if the test was positive at a concentration of HPV DNA 1 pg/mL or greater.

Quality of colposcopy and treatment: data from the national survey of Italian organised cervical screening programmes.

We collected from Italian organised cervical screening programmes data (a) on the correlation between colposcopic findings (according to the 1990 international classification) and histology and (b) on the treatment/management of screen-detected histologically confirmed cervical intraepithelial neoplasia (CIN). Data routinely recorded by organised programmes was provided as aggregated tables. We obtained data on colpo-histological correlation from 41 programmes.

National survey of the quality of 2nd level in screening for cervical cancer.

We collected, from the local registration systems of Italian organised cervical screening programmes, aggregated data (a) on the correlation between colposcopic grading and histology in routine colposcopies and (b) on treatment performed for screen-detected biopsy-proven cervical intraepithelial lesions (CIN). We obtained data on colpo-histological correlation from 40 programmes, reporting on 12,901 colposcopies, classified according to the 1990 international classification. Among them 37% were classified as normal and 25% as unsatisfactory (transformation zone not entirely visible).

Stereoselective syntheses of highly functionalized bicyclo[3.1.0]hexanes: a general methodology for the synthesis of potent and selective mGluR2/3 agonists.

[Chemical reaction: See text] A Et3Al mediated intramolecular epoxide opening, cyclopropanation reaction is described. The transformation provided highly functionalized bicyclo[3.1.

Practical synthesis of a neuropeptide Y antagonist via stereoselective addition to a ketene.

[Reaction: see text]. The synthesis of neuropeptide Y antagonist 1, currently under clinical investigation for the treatment of obesity, is described. The convergent synthesis from trans-spirolactone carboxylic acid intermediate 2a and aminopyrazole 3 is predicated on a stereoselective route to the former.

Palladium-catalyzed regioselective arylation of imidazo[1,2-b][1,2,4]triazine: synthesis of an alpha 2/3-selective GABA agonist.

A convergent, practical, and efficient synthesis of 2',6-difluoro-5'-[3-(1-hydroxy-1-methylethyl)imidazo[1,2-b][1,2,4]triazin-7-yl]biphenyl-2-carbonitrile (1), an orally active GABA(A) alpha(2/3)-selective agonist, is described. The seven-step, chromatography-free synthesis was demonstrated on a multi-kilogram scale and utilized biaryl bromide 6 and imidazotriazine 22 as key intermediates. Biaryl bromide 6 was prepared via a highly selective aromatic bromination.

An efficient chemoenzymatic approach to (S)-gamma-fluoroleucine ethyl ester.

[reaction: see text] An asymmetric synthesis of (S)-gamma-fluoroleucine ethyl ester 1 is described. The key transformation involves a lipase-catalyzed dynamic ring-opening of 2-(3-butenyl)azlactone 7b with EtOH to give amide ester (S)-6b in 84% enantiomeric excess. Removal of the N-pentenoyl group with N,N'-dibromodimethylhydantoin in the presence of trifluoroacetic acid afforded the titled compound, which was isolated as its hydrogen sulfate salt in 75% yield and >97% ee.

Preparation of enamides via palladium-catalyzed amidation of enol tosylates.

[reaction: see text] A Pd-catalyzed coupling of enol tosylates and amides has been developed. Ligand screening revealed dipf as the most general ligand for this transformation. A variety of enol tosylates were coupled to an array of enamides in 58-97% yield.

Unprecedented catalytic asymmetric reduction of N-H imines.

[Reaction: see text] Addition of lithium bis(trimethylsilyl)amide to perfluorinated ketones 1a-j affords (E)-N-TMS-ketimines 2a-j that are reduced in situ to afford racemic perfluoromethylated amine hydrochloride salts 3a-j in 54-97% yields. Solvolysis of the N-Si bond in MeOH leads to formation of bench-stable, isolable N-H imine Z/E isomer mixtures along with a methanol adduct. Enantioselective reduction of these three-component mixtures provides the first catalytic asymmetric synthesis of trifluoromethylated amines in 72-95% yields and 75-98% ee.

Methods for the synthesis of 5,6,7,8-tetrahydro-1,8-naphthyridine fragments for alphaVbeta3 integrin antagonists.

The preparation of 3-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)propan-1-amine 2a and 3-[(7R)-7-methyl-5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl]propan-1-amine 2b, key intermediates in the synthesis of alpha(V)beta(3) antagonists, is described. The syntheses rely on the efficient double Sonogashira reactions of 2,5-dibromopyridine 3 with acetylenic alcohols 4a/4b and protected propargylamines 10a-e followed by Chichibabin cyclizations of 3,3'-pyridine-2,5-diyldipropan-1-amines 9a/9b.

Enantioselective preparation of ring-fused 1-fluorocyclopropane-1-carboxylate derivatives: en route to mGluR 2 receptor agonist MGS0028.

[reaction: see text] An approach to the densely functionalized fluorocyclopropane 14, a key framework toward the synthesis of mGluR 2 receptor agonist MGS0028 (1) is reported. The Trost AAA reaction enantioselectively introduced the key allylic stereogenic center and the alpha-fluoroester moiety. Stereoselective epoxidation followed by intramolecular epoxide ring opening efficiently constructed the 1-fluorocyclopropane-1-carboxylate matrix.

Practical synthesis of a potent hepatitis C virus RNA replication inhibitor.

A practical, efficient synthesis of 1, a hepatitis C virus RNA replication inhibitor, is described. Starting with the inexpensive diacetone glucose, the 12-step synthesis features a novel stereoselective rearrangement to prepare the key crystalline furanose diol intermediate. This is followed by a highly selective glycosidation to couple the C-2 branched furanose epoxide with deazapurine.

An efficient asymmetric synthesis of an estrogen receptor modulator by sulfoxide-directed borane reduction.

An efficient asymmetric synthesis of a selective estrogen receptor modulator (SERM) that has a dihydrobenzoxathiin core structure bearing two stereogenic centers is reported. The stereogenic centers were established by an unprecedented chiral sulfoxide-directed stereospecific reduction of an alpha,beta-unsaturated sulfoxide to the saturated sulfide in one step. Studies to elucidate the mechanism for this reduction are reported.

An efficient synthesis of an alphavbeta3 antagonist.

A practical preparation of an alpha(v)beta(3) antagonist is reported. The antagonist consists of three key components, a tetrahydronaphthyridine moiety, a beta-alanine moiety, and a central imidazolidone moiety. The tetrahydronaphthyridine component was prepared using two different methods, both of which relied on variations of the Friedländer reaction to establish the desired regiochemistry.

Oxazolidine ring opening and isomerization to (E)-imines. Asymmetric synthesis of aryl-alpha-fluoroalkyl amino alcohols.

[reaction: see text] A base-induced ring opening/imine isomerization/diastereoselective organometallic addition sequence on 4-substituted 2-perfluoroalkyl-1,3-oxazolidines has been developed for the asymmetric synthesis of aryl alpha-perfluoroalkylamine derivatives. This practical method provides chiral amino alcohols in 60-95% yield with uniformely high diastereoselectivities ranging from 35:1 to >100:1.

Facile synthesis of 2-bromo-3-fluorobenzonitrile: an application and study of the halodeboronation of aryl boronic acids.

A scaleable synthesis of 2-bromo-3-fluorobenzonitrile via the NaOMe-catalyzed bromodeboronation of 2-cyano-6-fluorophenylboronic acid was developed. The generality of this transformation was demonstrated through the halodeboronation of a series of aryl boronic acids. Both aryl bromides and aryl chlorides were formed in good to excellent yields when the corresponding aryl boronic acid was treated with 1,3-dihalo-5,5-dimethylhydantoin and 5 mol % NaOMe.