Early brain amyloidosis in APP/PS1 mice with serum insulin-like growth factor-I deficiency.

The influence of insulin-like growth factor I (IGF-I) on the progression of Alzheimer's disease (AD) is discussed controversially. To help clarify the role of this circulating neurotrophic factor in brain amyloidosis, the major pathological trait in AD, we analyzed plaque formation in a mouse model of AD transgenic for human APP and PS1 mutations with reduced serum IGF-I levels (LIDAD mice). We found that brain amyloidosis in LIDAD mice appeared earlier than in AD mice, at 2 months of age, while attained comparable levels at 6 months. In parallel, early microgliosis was observed in LIDAD mice also at 2 months and remained exacerbated at 6 months. Collectively, these observations suggest a role of serum IGF-I in delaying early brain amyloidosis.

Properties and applications of the average interparticle distance.

The first and second moment operators are used to define the origin invariant shape and size of a molecule or functional group, as well as expressions for the distance between two electrons and the distance between an electron and a nucleus. The measure of molecular size correlates quite well with an existing theoretical measure of molecular volume calculated from isodensity contours. Also, the measure of size is effective in predicting steric effects of substituents which have been measured experimentally. The electron-electron and electron-nuclear distances are related to components of the Hartree-Fock energy. The average distance between two-electrons can model the Coulomb energy quite well, especially in the case of localized molecular orbitals. The average distance between an electron and a nucleus is closely related to the electron-nuclear attraction energy of a molecule.

Deletion of the Coffin-Lowry syndrome gene Rsk2 in mice is associated with impaired spatial learning and reduced control of exploratory behavior.

Coffin-Lowry Syndrome (CLS) is an X-linked syndromic form of mental retardation associated with skeletal abnormalities. It is caused by mutations of the Rsk2 gene, which encodes a growth factor regulated kinase. Gene deletion studies in mice have shown an essential role for the Rsk2 gene in osteoblast differentiation and function, establishing a causal link between Rsk2 deficiency and skeletal abnormalities of CLS. Although analyses in mice have revealed prominent expression of Rsk2 in brain structures that are essential for learning and memory, evidence at the behavioral level for an involvement of Rsk2 in cognitive function is still lacking. Here, we have examined Rsk2-deficient mice in two extensive batteries of behavioral tests, which were conducted independently in two laboratories in Zurich (Switzerland) and Orsay (France). Despite the known reduction of bone mass, all parameters of motor function were normal, confirming the suitability of Rsk2-deficient mice for behavioral testing. Rsk2-deficient mice showed a mild impairment of spatial working memory, delayed acquisition of a spatial reference memory task and long-term spatial memory deficits. In contrast, associative and recognition memory, as well as the habituation of exploratory activity were normal. Our studies also revealed mild signs of disinhibition in exploratory activity, as well as a difficulty to adapt to new test environments, which likely contributed to the learning impairments displayed by Rsk2-deficient mice. The observed behavioral changes are in line with observations made in other mouse models of human mental retardation and support a role of Rsk2 in cognitive functions.

Effects of rearing conditions on sand digging efficiency in juvenile cuttlefish.

The effect of environment on the maturation of sand digging behaviour in cuttlefish was studied. Sand digging behaviour of cuttlefish individually reared on sand was daily observed in their rearing tanks (first study). Other cuttlefish were individually reared from hatching to 2 weeks of life in different conditions (Group A, on a sandy substrate and group B, without sand). At days 0, 3, 6, 9, 12 and 15, cuttlefish from Groups A and B were placed in a novel tank, the bottom of which was covered by sand (second study). The first study shows that more and more cuttlefish sand dig in their rearing tank during the first 6 days of life. The second study shows that, confronted with a novel sand bottom, cuttlefish from Group A show shorter latencies of sand digging and they cover more completely than do cuttlefish from Group B. This indicates that the developmental changes in sand digging appear not totally pre-programmed, but at least partially experience-dependent. Presence of sand in rearing tanks may allow cuttlefish to acquire experience of digging to make this behaviour more efficient.

Lower respiratory tract infections in adults: non-antibiotic prescriptions by GPs.

BACKGROUND: The AIR II study is a prospective multicentre assessing management of lower respiratory tract infections (LRTIs) in adults by general practitioners (GPs). Epidemiological studies generally address the prescriptions of antibiotics. To our knowledge, little is known about the real impact of non-antibiotic therapeutic prescriptions (defined here as co-prescriptions) in LRTI. Therefore, the aim of the study was to evaluate non-antibiotic prescriptions in LRTIs. METHODS: Two thousand general practitioners (GPs) were randomly selected and asked to participate in each of 30 predefined areas covering mainland France. The patient's sociomedical record was completed by the GP during the consultation and sent to the data processing centre at the same time as an anonymous copy of his prescription. The GP also had to report the inclusion by telephone and agree to a telephone appointment with an interviewer. RESULTS: GPs (n = 3144) reported 5469 evaluable cases. Pneumonia accounted for 9.6% of diagnoses, acute exacerbations of chronic bronchitis 14.9% and acute bronchitis 72.5%. Antibiotics were prescribed to 96.5% of patients. In addition to the 5270 prescriptions of antibiotics, co-prescriptions proved to be twice as numerous as prescriptions of antibiotics (10,027 prescriptions for 5115 patients). Mucomodifiers, steroidal anti-inflammatory drugs and bronchodilators were significantly more prescribed in AECB than others. Non-steroidal anti-inflammatory drugs and antitussives were significantly more prescribed in acute bronchitis than AECB or CAP. CONCLUSIONS: Our results suggest that recommendations of management in LRTIs need to take into account co-prescriptions.

Management of lower respiratory tract infections by French general practitioners: the AIR II study. Analyse Infections Respiratoires.

The Analyse Infections Respiratoires (AIR) II study is a prospective, multicentre survey of the management of lower respiratory tract infections in patients aged 15-65 yrs by general practitioners (GPs) in France. To obtain real-time data recording, practitioners were required to submit an anonymous copy of their drug prescriptions. They were then interviewed over the telephone about the patients' sociodemographic data, signs and symptoms, as well as their presumptive diagnosis and the investigations they had decided upon. GPs (n=3,144) reported 5,469 evaluable cases. Pneumonia accounted for 9.6% of diagnoses, acute exacerbations of chronic bronchitis 14.9% and acute bronchitis 72.5%. The symptomatology covered an extremely wide range of clinical features, which, although statistically different in terms of incidence, overlapped to a large extent across diagnoses. By contrast, hospitalization, investigations or referral to a specialist were much more prevalent in pneumonia, although still very infrequent in general terms (0.5, 1.2 and 10.8%, respectively). Antibiotics were prescribed in 96.5% of patients, with minor differences between diagnoses. However, other medications such as nonsteroid, anti-inflammatory drugs, steroids, nonspecific antitussives and bronchial liquefiers accounted for two-thirds of the prescriptions. This study demonstrates the lower respiratory tract infections encountered by general practitioners are usually mild. However, antibiotic prescription was more systematic than in previous studies and the prescription of nonspecific symptomatic treatments was twice as frequent. General practitioners did not perform additional examinations or refer on a regular basis. There was a high prescription rate for symptomatic treatment.

Nonplanar aromatic compounds. 5. A atrategy for the synthesis of cis-10b,10c-dimethyl-10b,10c-dihydropyrenes. First crystal structure of a cis-10b,10c-dimethyl-10b,10c-dihydropyrene.

Through the use of a potentially removable tether, a heavily substituted 10b,10c-dimethyl-10b,10c-dihydropyrene (DMDHP), 20, was synthesized exclusively as the cis-isomer. It exists as the major component (20:1) in an equilibrium with its valence isomer syn-[2.2]metacyclophanediene 19. An X-ray crystal structure determination of 20, a cis-(2,7)-10b,10c-dihydropyrenophane, provided the first experimental measurements of the cis-DMDHP skeleton. The observed bond alternation in the [14]annulene was found to be larger than that of the corresponding trans-DMDHP framework. Prior MMPI calculations, on which previous discussion of the structure of the cis-DMDHP system had been based, are in very good agreement with the experimental results. Our own DFT calculations predict a more symmetric and more bond equalized structure than was observed in 20.

[Management of lower respiratory tract infections by general practitioners in France]. / Prise en charge des infections respiratoires basses en médecine générale en France.

OBJECTIVE: The purpose of this study was to describe the diagnostic and therapeutic strategies used by general practitioners (GPs) in patients with lower respiratory tract infections (LRTI). METHODS: Four hundred fifty GPs practicing in France participated in the study; they included 804 patients. The GP recorded social and demographic data and their prescription on a data sheet and responded to a phone questionnaire about their strategy. RESULTS: Most of the LRTI were acute bronchitis (72%); pneumonia and acute exacerbations of chronic bronchitis were observed respectively in 11% of the patients recruited. Diagnostic criteria used by the GPs were generally auscultation signs in patients with fever, cough and expectoration. Specialized advice (always a chest physician) and hospitalization were exceptional. Prescription of complementary exams was strongly related to the diagnosis of pneumonia (OR = 33.3; CI0.95: 15.48-70.4). Sick leaves were related to general symptoms (fever, asthenia). Antibiotics were prescribed in 95.7% of the patients, mainly aminopenicillin (40.4%) and macrolides (33.2%). Nonsteroidal or steroidal antiinflammatory drugs were prescribed in 72.5% of the patients irrespective of the LRTI diagnosis. DISCUSSION: The fact that GPs do not often refer patients to specialists or order hospitalization confirms their important role in setting up recommendations. It would also be necessary to develop an education program on better use of antibiotics targeted to GPs and patients.

Endo-exo and facial stereoselectivity in the Diels-Alder reactions of 3-substituted cyclopropenes with butadiene.

A computational examination of the four modes of addition in the Diels-Alder reactions of 3-substituted cyclopropene derivatives (substituents: BH(2), CH(3), SiH(3), NH(2), PH(2), OH, SH, F, and Cl) with butadiene have been carried out at the B3LYP/6-31++G(d)//HF/6-31++G(d) level. The degree of stabilization of these derivatives at the ground state correlates with the electronegativity of the substituent. This attenuation of reactivity and differences in steric interactions are the only factors needed to explain both the high facial selectivity and the differences in the endo-exo selectivity seen in these reactions. Furthermore, evidence is presented that indicates that stabilization by an interaction involving the syn C-3 hydrogen of cyclopropene and butadiene is small or irrelevant in controlling the endo-exo selectivity of the Diels-Alder reaction.

Phase II trial of paclitaxel and carboplatin in metastatic small-cell lung cancer: a Groupe Français de Pneumo-Cancérologie study.

PURPOSE: To evaluate the efficacy and safety of paclitaxel and carboplatin in the treatment of previously untreated patients with metastatic small-cell lung cancer (SCLC). PATIENTS AND METHODS: Eligible patients were aged 18 to 75 years with an Eastern Cooperative Oncology Group (ECOG) score < or = 2 and life expectancy > or = 12 weeks. Paclitaxel (200 mg/m(2)) was infused over 3 hours, before carboplatin (area under the curve [AUC] 6; Calvert formula) infused over 1 hour, once every 3 weeks for six cycles maximum. Prednisolone, dexchlorpheniramine, and ranitidine were standard premedication. Response to treatment was assessed every two cycles, and nonresponding patients were withdrawn from the trial to receive standard chemotherapy. RESULTS: Of the 50 patients entering the study, 48 and 46 patients were assessable for toxicity and response, respectively. The overall response rate was 65%, with complete responses in three patients. Five patients had stable disease (11%) and 11 patients experienced progressive disease (24%). Median survival was 38 weeks, and median duration of response was 20 weeks. One-year survival was 22.5%. For a total of 232 cycles, grade 3 and 4 toxicity was 33% for neutropenia, 3.5% for thrombocytopenia, and 4% for anemia. Four patients had neutropenic fever (one toxic death). Nonhematologic toxicity was mainly grade 1 and 2 paresthesia (21% of patients); grade 3 myalgia/arthralgia was observed in 6.5% of patients. CONCLUSION: First-line chemotherapy with paclitaxel and carboplatin in metastatic SCLC achieved a response rate and survival similar to standard regimens. With 1-day administration and a tolerable toxicity profile, this combination merits further investigation.

Use of binaural beat tapes for treatment of anxiety: a pilot study of tape preference and outcomes.

CONTEXT: Recent studies and anecdotal reports suggest that binaural auditory beats can affect mood, performance on vigilance tasks, and anxiety. OBJECTIVE: To determine whether mildly anxious people would report decreased anxiety after listening daily for 1 month to tapes imbedded with tones that create binaural beats, and whether they would show a definite tape preference among 3 tapes. DESIGN: A 1-group pre-posttest pilot study. SETTING: Patients' homes. PARTICIPANTS: A volunteer sample of 15 mildly anxious patients seen in the Clinique Psyché, Montreal, Quebec. INTERVENTION: Participants were asked to listen at least 5 times weekly for 4 weeks to 1 or more of 3 music tapes containing tones that produce binaural beats in the electroencephalogram delta/theta frequency range. Participants also were asked to record tape usage, tape preference, and anxiety ratings in a journal before and after listening to the tape or tapes. MAIN OUTCOME MEASURES: Anxiety ratings before and after tape listening, pre- and post-study State-Trait Anxiety Inventory scores, and tape preferences documented in daily journals. RESULTS: Listening to the binaural beat tapes resulted in a significant reduction in the anxiety score reported daily in patients' diaries. The number of times participants listened to the tapes in 4 weeks ranged from 10 to 17 (an average of 1.4 to 2.4 times per week) for approximately 30 minutes per session. End-of-study tape preferences indicated that slightly more participants preferred tape B, with its pronounced and extended patterns of binaural beats, over tapes A and C. Changes in pre- and posttest listening State-Trait Anxiety Inventory scores trended toward a reduction of anxiety, but these differences were not statistically significant. CONCLUSIONS: Listening to binaural beat tapes in the delta/theta electroencephalogram range may be beneficial in reducing mild anxiety. Future studies should account for music preference among participants and include age as a factor in outcomes, incentives to foster tape listening, and a physiologic measure of anxiety reduction. A controlled trial that includes binaural beat tapes as an adjunctive treatment to conventional therapy for mild anxiety may be warranted.

Predictors of physical outcomes in pediatric bone marrow transplantation.

The purpose of the present study was to investigate the hypothesis that family factors, in conjunction with clinical factors, are associated with physical outcomes in pediatric BMT. A prospective study of 68 pediatric patients (mean age = 7.5 years; ranging from 4 months to 18 years) undergoing BMT was carried out over a 6.5 year period. Physicians rated initial prognosis on a (0-5) scale which incorporated the child's diagnosis, known risk factors, and type of donor. Both parents individually completed two psychometrically sound questionnaires assessing family well-being and marital satisfaction. Cox proportional hazards survival analyses were performed to determine predictors of death (44% of the patients died). Potential predictor variables included were: initial prognosis, type of transplant, patient's age, socioeconomic status, marital satisfaction and family status, and family stress. Initial prognosis, as estimated by the physician, (RR = 0.62, 95% CI = 0.40, 0.97) was the best predictor of survival. Initial clinical factors are clearly critical in outcomes for pediatric BMT patients.

[Pristinamycin in the treatment of acute communicable pneumopathies in adults]. / La place de la pristinamycine dans les pneumopathies aiguës communautaires de l'adulte.

ALTERNATIVE TO BETA-LACTAMS: Due to the rapid and increasing development of resistance in the two main bacteria, S. pneumoniae and H. influenzae, it is important to determine whether pristinamycin, with known efficacy against these germs, could be a useful alternative to beta-lactams for the treatment of adult acute community-acquired pneumonia. PRISTINAMYCIN VS AMOXICILLIN/CLAVULANIC ACID: A double-blind placebo-controlled randomized multicentric study with two treatment arms enrolling hospitalized patients was conducted. Pristinamycin, 1 g b.i.d., demonstrated an efficacy equivalent to that of the amoxicillin/clavulanic acid combination, 500 mg x 4/d. IN CLINICAL PRACTICE: Pristinamycin is effective for the treatment of community-acquired pneumonia. Comparative studies including a large number of penicillin-resistant pneumococci remain to be performed, but the first intention use of pristinamycin is already fully warranted in patients at risk treated in an outpatient setting.

[Draft of the Aix-en Provence pollen calendar]. / Ebauche du calendrier pollinique d'Aix-en-Provence.

Because of some divergences between the pathologics of Aix and the pollinic accounts found by the spore-trap of Marseilles, a spore-trap has been installed since the beginning of 1997 in Aix hospital to prove that these two sites are specific for pollen identification and dates of pollinisation as well. After three years of measures, the correlation between the vegetation of Aix and the pathological symptoms is established. They are coherent with those published in other sound European countries and confirm the "mediterreean" feature of Aix.

Carboplatin as radiosensitizer in non-small cell lung cancer after cisplatin containing chemotherapy. A phase I study of a groupe francais de pneumo-cancerologie (G.F.P.C.).

A Phase I trial of carboplatin therapy was performed on patients with locally advanced non-small cell lung cancer who had been previously treated with cisplatin, mitomycin and a vinca aklaloïd. This was administered as a daily bolus infusion or as a continuous infusion for 6 weeks with concurrent daily thoracic radiation. All patients had to be objective responders or to show no change after chemotherapy. The carboplatin was started at 10 mg/m2 per day, and increased to 15 mg/m2 per day and 20 mg/m2 per day, if treatment was feasible in successive cohorts of at least six patients. The radiation therapy consisted of 62-66 Gray on the tumor and the ipsilateral mediastinal nodes, 50 Gray on the mediastinum and 40-45 Gray on the supraclavicular lymph nodes. Twenty-nine patients took part in this study. Thrombocytopenia was the principal dose-limiting toxicity, with 15 mg/m2 per day of bolus or continuous infusion. Other toxicities included a fall in haemoglobin level, a fall in white-blood cell count, nausea and vomiting. The median survival time was 12 months, but the response rate cannot be determined among patients selected on the basis of response to chemotherapy. The recommended Phase II dose for patients previously treated with cisplatin containing chemotherapy, is 10 mg/m2 per day of either a bolus or continuous infusion.