Use of prostaglandin E1 ovules in the therapeutic interruption of pregnancy in the 2d and 3d trimesters. Apropos of 46 cases

46 late interruptions of pregnancy (16 to 33 weeks of amenorrhea) were performed with the use of prostaglandins E1 ovules, of 1 mg, placed in the posterior vaginal cul-de-sac every 12 hours. It concerned 13 deaths in utero or extremely premature rupture of the membranes, 25 fetal indications (9 chromosomal abnormalities and 16 severe malformations), and 8 maternal indications. The efficacy was good either with ovules alone (84.7%) or associated with a balloon probe (5.3%). Expulsion is faster in the case of fetal deaths (average = 8 hours), than in therapeutic interruptions of pregnancy (average = 20 hours). The necessary doses did not exceed 3 mg of PgE1. There were very few side effects, essentially gastro-intestinal in nature and the course was simple. No obstetrical complication was noted. This method is therefore particularly effective with minimal side effects. Easy to use, it must be reserved for very precise indications.     

Anti-P30 IgA antibodies as prenatal markers of congenital toxoplasma infection

This study extends a previous study and confirms that the detection of anti-P30 IgA antibodies is very helpful in the diagnosis of acute acquired or congenital toxoplasmosis. Moreover, we demonstrate that an anti-P30 IgA response can be mounted in the fetuses infected by Toxoplasma gondii during their intra-uterine life as early as week 23 of gestation. A double-sandwich ELISA described in our previous work was used to detect anti-P30 IgA antibodies in 1378 human serum samples collected from 551 patients, including 162 fetuses whose mothers had been infected by T. gondii during pregnancy, 46 congenitally infected and 90 uninfected newborns and 253 women suspected of having been infected during pregnancy, including the mothers of fetuses and newborns previously described. Anti-P30 IgA antibodies were detected in all cases of acute toxoplasmosis but in no case of chronic toxoplasmosis: in the majority of cases, the IgA antibody titre fell below cut-off in 3-9 months. Among the 46 congenitally infected newborns, anti-P30 IgA antibodies were detected in sera of 41 infected newborns (38 at birth, two in the first months of life, one in the seventh month of life), while anti-P30 IgM antibodies were detected in only 30 cases at birth and in one case during the first month of life. Among 162 fetuses, anti-P30 IgA response was observed in five infected fetuses, but was not detected in either 152 uninfected fetuses or in five fetuses considered as infected. The absence or presence of anti-P30 IgA antibodies in the fetus is discussed in relation to the date of maternal infection and collection of the fetal blood. It clearly appears from our study that the combined testing of both IgM and IgA in the fetus and the newborn is essential for a more efficient diagnosis of infection.     

In vivo autofluorescence imaging of early cancers in the human tracheobronchial tree with a spectrally optimized system

The changes in the autofluorescence characteristics of the bronchial tissue is of crucial interest as a cancer diagnostic tool. Evidence exists that this native fluorescence or autofluorescence of bronchial tissues changes when they turn dysplastic and to carcinoma in situ. There is good agreement that the lesions display a decrease of autofluorescence in the green region of the spectrum under illumination with violet-light, and a relative increase in the red region of the spectrum is often reported. Imaging devices rely on this principle to detect early cancerous lesions in the bronchi. Based on a spectroscopic study, an industrial imaging prototype is developed to detect early cancerous lesions in collaboration with the firm Richard Wolf Endoskope GmbH, Germany. A preliminary clinical trial involving 20 patients with this spectrally optimized system shows that the autofluorescence can help to detect most lesions that would otherwise have remained invisible to an experienced endoscopist under white light illumination. A systematic off line analysis of the autofluorescence images pointed out that real-time decisional functions can be defined to reduce the number of false positive results. Using this method, a positive predictive value (PPV) of 75% is reached using autofluorescence only. Moreover, a PPV of 100% is obtained, when combining the white light (WL) mode and the autofluorescence (AF) mode, at the applied conditions. Furthermore, the sensitivity is estimated to be twice higher in the AF mode than in WL mode.     

Meta-analysis of the association of beta2-adrenergic receptor polymorphisms with asthma phenotypes

BACKGROUND: Two common polymorphisms of the beta2-adrenergic receptor gene (Arg16Gly and Gln27Glu ) have been extensively studied for their possible association with asthma-related phenotypes, but the results of individual studies have been inconclusive. OBJECTIVE: We aimed to integrate quantitatively the available evidence on the association of the Arg16Gly and the Gln27Glu polymorphisms with asthma, nocturnal asthma, asthma severity, and bronchial hyperresponsiveness. METHODS: Meta-analysis of case-control and cohort studies using random effects models. RESULTS: A total of 28 studies were included in the meta-analysis. The summary estimates suggested that neither the Gly16 nor the Glu27 allele contributes to asthma susceptibility overall (odds ratio [OR], 1.01; 95% CI, 0.90-1.13; and OR, 0.95; 95% CI, 0.83-1.09, respectively) or to bronchial hyperresponsiveness (OR, 0.90; 95% CI, 0.77-1.05; and OR, 1.07; 95% CI, 0.94-1.22, respectively). There was a strong association of Gly16 with nocturnal asthma (OR, 2.20; 95% CI, 1.56-3.11) and a less strong association with severe or moderate rather than milder asthma (OR, 1.42; 95% CI, 1.04-1.94). No such effects were seen for the Glu27 allele (OR, 1.02; 95% CI, 0.74-1.40; and OR, 0.82; 95% CI, 0.59-1.14, respectively). Moreover, there was evidence that Gly16 homozygotes had a much higher risk for nocturnal asthma (OR, 5.15; 95% CI, 2.44-10.84) and asthma severity (OR, 2.84; 95% CI, 1.62-4.96) than the Arg16 homozygotes. CONCLUSION: The Gly16 allele of the beta2-adrenergic receptor gene predisposes to nocturnal asthma, and this may also explain the association with asthma severity. Neither polymorphism modulates the risk for bronchial hyperresponsiveness or mild asthma.     

Reporting of conflicts of interest in guidelines of preventive and therapeutic interventions

Background

Guidelines published in major medical journals are very influential in determining clinical practice. It would be essential to evaluate whether conflicts of interests are disclosed in these publications. We evaluated the reporting of conflicts of interest and the factors that may affect such disclosure in a sample of 191 guidelines on therapeutic and/or preventive measures published in 6 major clinical journals (Annals of Internal Medicine, BMJ, JAMA, Lancet, New England Journal of Medicine, Pediatrics) in 1979, 1984, 1989, 1994 and 1999.

Results

Only 7 guidelines (3.7%) mentioned conflicts of interest and all were published in 1999 (17.5% (7/40) of guidelines published in 1999 alone). Reporting of conflicts of interest differed significantly by journal (p=0.026), availability of disclosure policy by the journal (p=0.043), source of funding (p < 0.001) and number of authors (p=0.004). In the entire database of 191 guidelines, a mere 18 authors disclosed a total of 24 potential conflicts of interest and most pertained to minor issues.

Conclusions

Despite some recent improvement, reporting of conflicts of interest in clinical guidelines published in influential journals is largely neglected.

     

In vivo autofluorescence spectroscopy of human bronchial tissue to optimize the detection and imaging of early cancers

We are developing an imaging system to detect pre-/early cancers in the tracheo-bronchial tree. Autofluorescence might be useful but many features remain suboptimal. We have studied the autofluorescence of human healthy, metaplastic and dysplastic/CIS bronchial tissue, covering excitation wavelengths from 350 to 480 nm. These measurements are performed with a spectrofluorometer whose distal end is designed to simulate the spectroscopic response of an imaging system using routine bronchoscopes. Our data provide information about the excitation and emission spectral ranges to be used in a dual range detection imaging system to maximize the tumor vs healthy and the tumor vs. inflammatory/metaplastic contrast in detecting pre-/early malignant lesions. We find that the excitation wavelengths yielding the highest contrasts are between 400 and 480 nm with a peak at 405 nm. We also find that the shape of the spectra of healthy tissue is similar to that of its inflammatory/metaplastic counterpart. Finally we find that, when the spectra are normalized, the region of divergence between the tumor and the nontumor spectra is consistently between 600 and 800 nm and that the transition wavelength between the two spectral regions is around 590 nm for all the spectra regardless of the excitation wavelength, thus suggesting that there might be one absorber or one fluorophore. The use of backscattered red light enhances the autofluorescence contrast.     

Glucose and free fatty acid utilization during prolonged exercise in prepubertal boys in relation to catecholamine responses

Summary Ten prepubertal boys performed 60-min cycle exercise at about 60% of their maximal oxygen uptake as previously measured. To measure packed cell volume, plasma glucose, free fatty acids (FFA), glycerol and catecholamines, blood samples were drawn at rest using a heparinized cathether and at the 15th, 30th and 60th min of the exercise and after 30 min of recovery. At rest, the blood glucose concentrations were at the lowest values for normal. Exercise induced a small decrease of blood glucose which was combined with an abrupt increase of the noradrenaline concentration during the first 15 min. The FFA and glycerol concentrations increased throughout the exercise linearly with that of adrenaline. Compared to adults, the FFA uptake expressed per minute and per litre of oxygen uptake was greater in children. These results suggested that it is difficult for children to maintain a constant blood glucose concentration and that prolonged exercise provided a real stimulus to hypoglycaemia. An immediate and large increase in noradrenaline concentration during exercise and a greater utilization of FFA was probably used by children to prevent hypoglycaemia.     

Factors That Predict 1-Year Incident Hip and Non-Hip Fractures for Home Care Recipients: A Linked-Data Retrospective Cohort Study

ObjectivesThe purpose of our study was to identify factors that predict 1-year incident hip and major osteoporotic non-hip fractures (ie, wrist, spine, pelvis, humerus) for home care recipients while accounting for the competing risk of death.DesignWe conducted a retrospective cohort study with linked population data.Setting and ParticipantsAll home care recipients in Ontario, Canada, receiving services for more than 6 months with an admission assessment between April 1, 2011, and March 31, 2015, were included.MethodsClinical data from the Resident Assessment Instrument Home Care were linked to fracture data from the Discharge Abstract Database and the National Acute Care Reporting System. Competing risk proportional hazard regressions using the Fine and Grey method were performed to model the association between potential risk factors and fracture.ResultsPrevious fall, previous fracture, cognitive impairment, unsteady gait, alcohol use, tobacco use, and Parkinson disease were consistently associated with all fracture types. Cognitive impairment (hazard ratio 2.09; 95% confidence interval 1.86–2.36) and wandering [1.66 (1.06–1.27)] were most predictive of hip fractures and being female [1.86 (1.76–1.98)] and experiencing a previous fracture [1.86 (1.76–1.98)] were most predictive of non-hip fractures. Risk factors unique to non-hip fractures as compared with hip fractures were locomotion ability outdoors and psychotropic medication use.Conclusions and ImplicationsOur results indicate that, in addition to typical fracture risk factors, home care recipients have unique characteristics that increase their risk. Fracture risk assessment tools and subsequent prevention strategies should be modified to accurately identify home care recipients at risk for imminent 1-year fracture.     

Two-stage Study of Familial Prostate Cancer by Whole-exome Sequencing and Custom Capture Identifies 10 Novel Genes Associated with the Risk of Prostate Cancer

BackgroundFamily history of prostate cancer (PCa) is a well-known risk factor, and both common and rare genetic variants are associated with the disease.ObjectiveTo detect new genetic variants associated with PCa, capitalizing on the role of family history and more aggressive PCa.Design, setting, and participantsA two-stage design was used. In stage one, whole-exome sequencing was used to identify potential risk alleles among affected men with a strong family history of disease or with more aggressive disease (491 cases and 429 controls). Aggressive disease was based on a sum of scores for Gleason score, node status, metastasis, tumor stage, prostate-specific antigen at diagnosis, systemic recurrence, and time to PCa death. Genes identified in stage one were screened in stage two using a custom-capture design in an independent set of 2917 cases and 1899 controls.Outcome measurements and statistical analysisFrequencies of genetic variants (singly or jointly in a gene) were compared between cases and controls.Results and limitationsEleven genes previously reported to be associated with PCa were detected (ATM, BRCA2, HOXB13, FAM111A, EMSY, HNF1B, KLK3, MSMB, PCAT1, PRSS3, and TERT), as well as an additional 10 novel genes (PABPC1, QK1, FAM114A1, MUC6, MYCBP2, RAPGEF4, RNASEH2B, ULK4, XPO7, and THAP3). Of these 10 novel genes, all but PABPC1 and ULK4 were primarily associated with the risk of aggressive PCa.ConclusionsOur approach demonstrates the advantage of gene sequencing in the search for genetic variants associated with PCa and the benefits of sampling patients with a strong family history of disease or an aggressive form of disease.Patient summaryMultiple genes are associated with prostate cancer (PCa) among men with a strong family history of this disease or among men with an aggressive form of PCa.