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Org 37462 1 is the active ingredient in Orgalutran®, an innovative product that reduces the time of treatment in in vitrofertilization from four to less than two weeks. Org 37462 is a synthetic decapeptide containing several amino acids that are unnatural in stereochemistry andor in structure. The synthesis, starting with a ProtectingGroupDAlaresin, is a typical solid state synthesis. For the conduction of several metabolism studies, Org 37462 had to be labelled with carbon 14. It was decided to label D32naphthylalanine, the last amino acid to be coupled to the resin. We report the synthesis of 14C and 14C3Org 37462, starting from 2bromo14Cmethylnaphthalene and 14C2tertbutyl glycinate. Copyright © 2008 John Wiley & Sons, Ltd.

La spécificité d’un hôpital universitaire est le plus souvent abordée sous l’angle de la charge d’enseignement et de recherche. L’enquête EPAGE, outil d’aide à la décision accessible sur Internet, nous a permis de comparer le recours à un acte courant, la colonoscopie, au CHU de Clermont-Ferrand et au CH de Moulins. L’objectif a été de mettre en évidence des différences de pratique de soins entre ces 2 centres proches géographiquement, qui traduiraient une spécificité hospitalo-universitaire non prise en compte dans le mode de financement de l’hôpital.

Background: Efforts to decrease overuse of health care may result in underuse. Overuse and underuse of colonoscopy have never been simultaneously evaluated in the same patient population. Methods: In this prospective observational study, the appropriateness and necessity of referral for colonoscopy were evaluated by using explicit criteria developed by a standardized expert panel method. Inappropriate referrals constituted overuse. Patients with necessary colonoscopy indications who were not referred constituted underuse. Consecutive ambulatory patients with lower gastrointestinal (GI) symptoms from 22 general practices in Switzerland, a country with ready access to colonoscopy, were enrolled during a 4-week period. Follow-up data were obtained at 3 months for patients who did not undergo a necessary colonoscopy. Results: Eight thousand seven hundred sixty patient visits were screened for inclusion; 651 patients (7.4%) had lower GI symptoms (mean age 56.4 years, 68% women). Of these, 78 (12%) were referred for colonoscopy. Indications for colonoscopy in 11 patients (14% of colonoscopy referrals or 1.7% of all patients with lower GI symptoms) were judged inappropriate. Among 573 patients not referred for the procedure, underuse ranged between 11% and 28% of all patients with lower GI symptoms, depending on the criteria used. Conclusions: Applying criteria from an expert panel of nationally recognized experts indicates that underuse of referral for colonoscopy exceeds overuse in primary care in Switzerland. To improve quality of care, both overuse and underuse of important procedures must be addressed. (Gastrointest Endosc 2000;52:593-9.)

Background: Increasing the appropriateness of use of upper gastrointestinal (GI) endoscopy is important to improve quality of care while at the same time containing costs. This study explored whether detailed explicit appropriateness criteria significantly improve the diagnostic yield of upper GI endoscopy. Methods: Consecutive patients referred for upper GI endoscopy at 6 centers (1 university hospital, 2 district hospitals, 3 gastroenterology practices) were prospectively included over a 6-month period. After controlling for disease presentation and patient characteristics, the relationship between the appropriateness of upper GI endoscopoy, as assessed by explicit Swiss criteria developed by the RAND/UCLA panel method, and the presence of relevant endoscopic lesions was analyzed. Results: A total of 2088 patients (60% outpatients, 57% men) were included. Analysis was restricted to the 1681 patients referred for diagnostic upper GI endoscopy. Forty-six percent of upper GI endoscopies were judged to be appropriate, 15% uncertain, and 39% inappropriate by the explicit criteria. No cancer was found in upper GI endoscopies judged to be inappropriate. Upper GI endoscopies judged appropriate or uncertain yielded significantly more relevant lesions (60%) than did those judged to be inappropriate (37%; odds ratio 2.6: 95% CI [2.2, 3.2]). In multivariate analyses, the diagnostic yield of upper GI endoscopy was significantly influenced by appropriateness, patient gender and age, treatment setting, and symptoms. Conclusions: Upper GI endoscopies performed for appropriate indications resulted in detecting significantly more clinically relevant lesions than did those performed for inappropriate indications. In addition, no upper GI endoscopy that resulted in a diagnosis of cancer was judged to be inappropriate. The use of such criteria improves patient selection for upper GI endoscopy and can thus contribute to efforts aimed at enhancing the quality and efficiency of care. (Gastrointest Endosc 2000;52:333-41).

We have developed criteria to determine the appropriate indications for lumbar laminectomy, using the standard procedure developed at the RAND corporation and the University of California at Los Angeles (RAND-UCLA). A panel of five surgeons and four physicians individually assessed 1000 hypothetical cases of sciatica, back pain only, symptoms of spinal stenosis, spondylolisthesis, miscellaneous indications or the need for repeat laminectomy. For the first round each member of the panel used a scale ranging from 1 (extremely inappropriate) to 9 (extremely appropriate). After discussion and condensation of the results into three categories laminectomy was considered appropriate in 11% of the 1000 theoretical scenarios, equivocal in 26% and inappropriate in 63%. There was some variation between the six categories of malalignment, but full agreement in 64% of the hypothetical cases.We applied these criteria retrospectively to the records of 196 patients who had had surgical treatment for herniated discs in one Swiss University hospital. We found that 48% of the operations were for appropriate indications, 29% for equivocal reasons and that 23% were inappropriate.The RAND-UCLA method is a feasible, useful and coherent approach to the study of the indications for laminectomy and related procedures, providing a number of important insights. Our conclusions now require validation by carefully designed prospective clinical trials, such as those which are used for new medical techniques.

To describe and compare both overuse and underuse of diagnostic upper gastrointestinal endoscopy in different settings.

It has been suggested that converting, via a process of cross-coding, the listing used by the Swiss Disability Insurance (SDI) for their statistics into codes of the International Classification of Impairments, Disabilities, and Handicaps (ICIDH) would improve the quality and international comparability of disability statistics for Switzerland. Using two different methods we tested the feasibility of this cross-coding on a consecutive sample of 204 insured persons, examined at one of the medical observation centres of the SDI. Cross-coding is impossible, for all practical purposes, in a proportion varying between 30% and 100%, depending on the method of cross-coding, the level of disablement and the required quality of the resulting codes. Failure is due to lack of validity of the SDI codes: diseases are poorly described, consequences of diseases (disability and handicap, including loss of earning capacity), insufficiently described or not at all. Assessment of disability and handicap would provide necessary information for the SDI. It is concluded that the SDI should promote the use of the ICIDH in Switzerland, especially among medical practitioners whose assessment of work capacity is the key element in the decision to award benefits or propose rehabilitation.

Optical redshifts of nine low-luminosity companions of early-type galaxies have been obtained as part of a study of the small-scale clustering properties of dwarf galaxies. The velocity differences between the low-luminosity companions and the nearest giant are typically less than 300 km s-1in the case of 'field' giants and larger for members of groups of galaxies. We speculate that early-type companions of isolated giant galaxies may be gravitationally bound satellites which can be used as dynamical probes of dark haloes, while in groups of galaxies they are free-floating in the general potential well of the group. The spectra of one nucleated dwarf elliptical and two dwarfs of composite dE and BCD morphology show evidence of recent star formation.

four IRAS galaxies. NGC 1620 is shown to have an off-center arclike structure of 3 kpc radius that may be the largest supernova-blown bubble known. UGC 2982 is an ongoing merger of two gas-rich galaxies. We show that the UGC 3004/3005 pair is not interacting despite the proximity of its components. UGC 3004 is a regular barred spiral galaxy. A second nucleus in the edge-on system UGC 3005 suggests a recent merger. Finally, IRAS 23385+0300 is one of the most infrared-luminous galaxies known.

The objective of this study was to estimate the incidence of hip fracture in the canton of Vaud, Switzerland (total population 584 000), for the period 1986–1991 using routine hospital discharge data collected by the Cantonal Service of Statistical Research and Information (SCRIS). For the survey period, the estimated average annual crude incidence rate of hip fractures was 167 per 100 000 persons aged 20 or older (241 for women and 84 for men). For the population aged 50 years or older, the crude incidence rate was 388 per 100 000 persons (546 for women and 185 for men). The average annual age-specific rates rose exponentially by successive 5-year age groups. The median age of patients at the time of the fracture was 82 years in women and 74 years in men. There was no significant difference between the total number of cervical and trochanteric fractures. Between the ages of 20 and 84 years, the cumulative risk for a woman to be admitted to hospital with a hip fracture was twice that of a man (15.8% vs 7.8%). From 1986 to 1991, the age- and sex-adjusted incidence, like the ratio of cervical to trochanteric fractures, did not show any significant trend, although it was consistent with an increase in men (p=0.09). However, the annual number of fractures rose from 644 to 776, particularly among very aged men. The mean length of stay in the acute care hospital fell from 38 days in 1986 to 25 days in 1991. Finally, the comparison of these results with those obtained in 1986 for the same population from more exhaustive sources has confirmed the provision of a consistent, although overestimated, assessment of hip fracture incidence by means of these routine hospital statistics in the canton of Vaud, Switzerland.

Examine the reproducibility of the RAND method for developing criteria for the appropriateness of medical procedures.

Quality of medical assessment of work incapacity has been poorly investigated, despite the enormous costs engendered by transient incapacity of work and permanent disability. This study examined some indices of quality from a stratified, random sample (n = 120) of assessments performed by expert assessors of the Swiss disability insurance. The distribution of work incapacity (WI) percentages over a 100% scale showed a clustering around key values significantly associated with financial disability benefits. The precision of WI, expressed as the level of quantitative exactness, was found to be high in 74% (95% CI: 66-82%) of current WI assessments, and in 62% (95% CI: 53-71%) of maximal WI assessments. Disagreement was observed in 17% of cases when comparing two ways of expressing WI by the same physician (95% CI: 10-23%). This exploratory study is limited by the general lack of objective criteria and standards. Further theoretical and empirical developments are needed to determine standardized criteria and clear guidelines for medical assessments of WI, as well as for evaluating their quality.

The structure of the title compound, C16H22O4, was determined by X-rays atT=290 K.Mr=264.320, triclinic, space groupP¯1,a=8.4857(9),b=10.0613(5),c=10.1499(7) Å,a=122.019(5)°,ß=107.049(8)°,?=74.892(9)°,Vc=696.5 Å3,Z=2,Dx=1.260 Mg m-3. MoKa radiation (graphite crystal monochromator,?=0.70926 Å),µ(MoKa)=7.03 cm-1. Final conventionalR-factor=0.058,Rw=0.088 for 2223 unique reflections and 247 variables. The structure was solved usingMultan andDirdif. The alkylation step in the synthetic preparation of clerodane-like compounds results in an equatorial position of the dioxolan group.

During a redshift survey of an infrared complete sample of galaxies recorded by the Infra-Red Astronomical Satellite (IRAS) we have identified the IRAS source 00275–2859 as a quasar with a redshift of z = 0.28. The object looks stellar on both blue and red photographic plates, with an apparent optical magnitude J = 17.1 mag. It is a radio source. Its far infrared luminosity is 1.5 ×lO12L ⊙, which exceeds both its optical and radio luminosity. This IRAS source is the second previously unidentified quasar selected through its infrared emission after IRAS source 13349 +24381. This suggests that the IRAS data contain a new class of quasars with strong internal reddening that possibly share the violent star formation activity of the most luminous IRAS objects.

A patient-oriented survey was conducted in Switzerland with the aim to establishing the distribution of medical X-ray examinations among the population. A sample of 1235 people aged between 15 and 74 y (589 males and 637 females) was contacted. The participants were asked to give the number of medical X-ray examinations performed during the previous 12 months. Three-fourths of the sample did not undergo any medical X-ray examination during a 12 month-period, and 10% of the population underwent more than 1 medical X-ray examination in a year. These results were independent of the geographic region. The age distributions of the participants who did not undergo any medical X-ray examination and those who underwent one medical X-ray examination were similar. On the other hand, the age distribution of the participants who underwent more than one medical X-ray examination was characterised by a higher contribution from the elderly.

The cyclic enones (I) and (V) are converted to the β‐phenylthio ketones (III) or (VI) which are then chlorinated and directly dehydrochlorinated to produce the β‐phenylthio α,β‐unsaturated cycloalkanones (IV) or (VII).

The aldehyde (XV) is considered as the key intermediate in the synthesis of dihydroclerodin (XVI).

Starting from the bromoethanol (I), the furofuran (VIII) possessing the relative stereochemistry of the natural insect antifeedant clerodanes is prepared, the key step being the reaction of the α‐lithio nitrile derived from (IV) with the oxirane (V).

The title compounds (X) and (XI) are prepared starting from γ‐butyrolactone (I).