BACKGROUND Cigarette smoking is associated with lower fecundity rates, adverse reproductive outcomes and a higher risk of IVF failures. Over the last few decades, prevalence of smoking among women of ...reproductive age has increased. This review focuses on current knowledge of the potential effects of smoke toxicants on all reproductive stages and the consequences of smoke exposure on reproductive functions. METHODS We conducted a systematic review of the scientific literature on the impact of cigarette smoking and smoke constituents on the different stages of reproductive function, including epidemiological, clinical and experimental studies. We attempted to create hypotheses and find explanations for the deleterious effects of cigarette smoke observed in experimental studies. RESULTS Cigarette smoke contains several thousand components (e.g. nicotine, polycyclic aromatic hydrocarbons and cadmium) with diverse effects. Each stage of reproductive function, folliculogenesis, steroidogenesis, embryo transport, endometrial receptivity, endometrial angiogenesis, uterine blood flow and uterine myometrium is a target for cigarette smoke components. The effects of cigarette smoke are dose-dependent and are influenced by the presence of other toxic substances and hormonal status. Individual sensitivity, dose, time and type of exposure also play a role in the impact of smoke constituents on human fertility. CONCLUSIONS All stages of reproductive functions are targets of cigarette smoke toxicants. Further studies are necessary to better understand the deleterious effects of cigarette smoke compounds on the reproductive system in order to improve health care, help to reduce cigarette smoking and provide a better knowledge of the molecular mechanisms involved in reproductive toxicology.
The impact of the first coronavirus disease 2019 (COVID-19) wave on cancer patient management was measured within the nationwide network of the Unicancer comprehensive cancer centers in France.
The ...number of patients diagnosed and treated within 17 of the 18 Unicancer centers was collected in 2020 and compared with that during the same periods between 2016 and 2019. Unicancer centers treat close to 20% of cancer patients in France yearly. The reduction in the number of patients attending the Unicancer centers was analyzed per regions and cancer types. The impact of delayed care on cancer-related deaths was calculated based on different hypotheses.
A 6.8% decrease in patients managed within Unicancer in the first 7 months of 2020 versus 2019 was observed. This reduction reached 21% during April and May, and was not compensated in June and July, nor later until November 2020. This reduction was observed only for newly diagnosed patients, while the clinical activity for previously diagnosed patients increased by 4% similar to previous years. The reduction was more pronounced in women, in breast and prostate cancers, and for patients without metastasis. Using an estimated hazard ratio of 1.06 per month of delay in diagnosis and treatment of new patients, we calculated that the delays observed in the 5-month period from March to July 2020 may result in an excess mortality due to cancer of 1000-6000 patients in coming years.
In this study, the delays in cancer patient management were observed only for newly diagnosed patients, more frequently in women, for breast cancer, prostate cancer, and nonmetastatic cancers. These delays may result is an excess risk of cancer-related deaths in the coming years.
•A reduction of the number of cancer patients attending cancer centers was observed in France from January to July 2020.•This reduction was observed only for newly diagnosed patients.•The reduction of new diagnosis was more pronounced in women, for breast cancer, and prostate cancer, and nonmetastatic cancer.•No compensation was observed for the last months of 2020. The magnitude of delays may be larger in centers within the same country.•An estimation of the excess cancer death resulting from these delays is presented.
Protracted deep coma after bromazepam poisoning Lakhal, K; Pallancher, S; Mathieu-Daude, J-C ...
International journal of clinical pharmacology and therapeutics
48, Issue:
1
Journal Article
Peer reviewed
Bromazepam intoxication is very common but surprisingly rarely reported.
We describe the case of a 73-year-old woman who suffered from a prolonged coma after acute self poisoning with bromazepam ...(serum concentration of 2,000 ng/ml at admission, 2 - 10 hours after ingestion of up to 180 mg) and zolpidem (900 ng/ml at admission). Only the former lasted at toxic concentrations. Recovery of consciousness allowed extubation on Day 16. Repeat-dose activated charcoal (25 g every 6 h from Day 14 to 16) resulted in minimal effects on bromazepam grossly estimated kinetics.
Despite its relatively low theoretic half-life, bromazepam may induce a prolonged life-threatening coma, even in the absence of renal or hepatic failure.
In the present paper, we report for the first time the tissue distribution of ibogaine and noribogaine, the main metabolite of ibogaine, in a 48-year-old Caucasian male, with a history of drug abuse, ...found dead at his home after a poisoning involving the ingestion of root bark from the shrub Tabernanthe iboga. Ibogaine and noribogaine were quantified in tissues and fluids using a fully validated liquid chromatography-electrospray mass spectrometry method. Apart from cardiac tissue, ibogaine and noribogaine were identified in all matrices investigated. The highest concentrations were found in spleen, liver, brain, and lung. The tissue/subclavian blood concentration ratios averaged 1.78, 3.75, 1.16, and 4.64 for ibogaine and 0.83, 2.43, 0.90, and 2.69 for noribogaine for spleen, liver, brain, and lung, respectively. Very low concentrations of the two drugs were found in the prostatic tissue. Both ibogaine and noribogaine are secreted in the bile and cross the blood-brain harrier. Four other compounds were detected in most of the studied matrices. One of them was identified as ibogamine. Unfortunately, we were not able to positively identify the other three compounds because of the unavailability of reference substances. Two of them could possibly be attributed to the following oxidation products: iboluteine and desmethoxyiboluteine. The third compound could be ibogaline.
A specific and sensitive liquid chromatography-electrospray ionization mass spectrometry (LC–ESI–MS) method was developed for the determination of free and total ropivacaine in human plasma. The ...work-up procedure involved a simple precipitation of plasma proteins with methanol. Etidocaine served as the internal standard. After microscale equilibrium-dialysis, measurement of free ropivacaine levels was performed after direct injection of the dialysate into the chromatograph. The system used a Zorbax eclipse XD8 C8 analytical column packed with 5
μm diameter particles as the stationary phase. The mobile phase consisted of a 15-min gradient (mobile phase A: 0.05% (v/v) trimethylamine in acetonitrile, mobile phase B: 2
mM ammonium formate buffer (pH 3)). Mass spectrometric data were acquired in single ion monitoring mode at
m/
z 275 for ropivacaine and
m/
z 277 for etidocaine. The drug/internal standard peak area ratios (plasma) or peak areas (dialysate) were linked via a quadratic relationship to concentrations. Precision ranged from 1 to 7.6% and accuracy was between 92.6 and 109%. The lower limits of quantitation were 1
μg/l in plasma and 2
μg/l in the dialysate. This method was found suitable for the analysis of plasma samples collected during a clinical trial performed in 30 infants undergoing epidural anaesthesia or continuous psoas compartment block.
This report, an audit requested by the French government, describes oncological patterns of care, prognostic factors, and survival for patients with newly diagnosed and histologically confirmed ...glioblastoma multiforme (GBM) in France. The French Brain Tumor DataBase, which is a national multidisciplinary (neurosurgeons, neuropathologists, radiotherapists, neurooncologists, epidemiologists, and biostatisticians) network, prospectively collected initial data for the cases of GBM in 2004, and a specific data card was used to retrospectively collect data on the management and follow-up care of these patients between January 1, 2004, and December 1, 2006. We recorded 952 cases of GBM (male/female ratio 1.6, median age 63.9 years, mean preoperative Karnofsky performance status KPS 79). Surgery consisted of resection (RS; n = 541) and biopsy (n = 411); 180 patients did not have subsequent oncological treatment. After surgery, first-line treatment (n = 772) consisted of radiotherapy (RT) and temozolomide (TMZ) concomitant +/− adjuvant in 314 patients, RT alone in 236 patients, chemotherapy (CT) alone in 157 patients, and other treatment modalities in 65 patients. Median overall survival was 286 days (95% CI, 266-314) and was significantly affected by age, KPS, and tumor location. Median survival (days, 95% CI) associated with these main strategies, when analyzed by a surgical group, were as follows: RS + RT-TMZ(
n
=224): 476 (441-506), biopsy + RT-TMZ(
n
=90): 329 (301-413), RS + RT(
n
=147): 363 (331-431), biopsy + RT(
n
=89): 178 (153-237), RS + CT(
n
=61): 245 (190-361), biopsy + CT(
n
=96): 244 (198-280), and biopsy only(
n
=118): 55 (46-71). This study illustrates the usefulness of a national brain tumor database. To our knowledge, this work is the largest report of recent GBM management in Europe.
Previous studies have described an important selenium deficiency in a mountain region (Glanle) in the west of Ivory Coast.
To assess the antioxidant capacity of subjects from a selenium deficient ...area in Ivory Coast (Glanle region).
This study involved 57 subjects, 18 to 69 years old, living in the Glanle region and 56 healthy controls living in the southern coastal region (Bodou). In the Glanle region families consume basically a vegetarian and crude palm oil diet, whereas in the Bodou region, families eat a fish-based diet with principally refined palm oil. Fasting blood samples were collected to assess the following parameters: lipid status (plasma total lipids; total-, HDL and LDL-cholesterol; triglycerides; phospholipids; fatty acid composition), plasma protein status (total protein, albumin, transthyretin, orosomucoid, CRP, transferrin), antioxidant capacity (plasma selenium, uric acid, retinol, alpha-tocopherol and tocotrienols levels, plasma seleno-glutathione peroxidase (GSHPx) activity) and oxidative stress markers (malondialdehyde (MDA) and advanced oxidation protein products (AOPP)).
The mountain region samples (Glanle) were characterized by significantly lower plasma albumin, total-, HDL- and LDL-cholesterol, retinol and selenium levels, plasma PUFA content and GSHPx activity, but significantly higher alpha-tocopherol index and total tocotrienol level, than controls from the coastal area (Bodou). These results suggest a higher exposure risk to oxidative stress for the mountain region subjects. However, the absence of oxidative damage in this group provides evidence of a selenium independent protection mechanism against oxidative stress. This protection is related to lower plasma LDL cholesterol and PUFA content, and to higher alpha-tocopherol index, delta and total tocotrienols.
The long-term consumption of crude palm oil could be considered as an effective protective factor against oxidative stress.
A specific and sensitive liquid chromatography-electrospray ionization mass spectrometry method was developed for the determination of ibogaine and noribogaine in human urine. The work-up procedure ...involved a solid phase extraction of the compounds and the internal standard (fluorescein) using Oasis HLB columns. The system used a Zorbax eclipse XDB C8 analytical column packed with 5µm diameter particles as the stationary phase. The mobile phase consisted of a 20-min gradient (mobile phase A: 0.02% (v/v) trimethylamine in acetonitrile, mobile phase B: 2 mM ammonium formate buffer (pH 3)). Mass spectrometric data were acquired in single ion monitoring mode at m/z 311.1, 297.2 and 333 for ibogaine, noribogaine and fluorescein, respectively. The drug/internal standard peak area ratios were linked via a quadratic relationship to concentrations (1.78−358 μg L⁻¹ for ibogaine; 2−400 μg L⁻¹ for noribogaine). Precision ranged from 5.8 to 14.8% and accuracy was between 93.2 and 112.9%. Mean extraction recoveries of ibogaine, noribogaine and fluorescein were 70.0, 81.7 and 94.8%, respectively. The extraction efficiency was independent of concentration over the range studied. The lower limits of quantitation were 1.78 μg L⁻¹ for ibogaine and 2 μg L⁻¹ for noribogaine. In this paper, extensive stability testing was undertaken using a wide range of storage conditions. This method was found suitable for urine analysis of a poisoning involving ingestion of drink made from powdered root of shrub Tabernanthe iboga.
The POLA study (June 1995 through July 1997) is a population-based study on cataract and age-related macular degeneration (AMD) and their risk factors in 2584 residents of Séte (South of France), ...aged 60-95 years. Classification of AMD was performed on 50° fundus photographs, according to an international classification. The presence of cardiovascular disease and its risk factors was determined by interviewer-based questionnaire, clinical examination (anthropometry, blood pressure) and fasting plasma measurements. Using a logistic model adjusted for age and gender, late AMD was not significantly associated with a history of cardiovascular disease, diabetes, use of hypocholesterolemic drugs, hypertension, blood pressure or plasma lipids. Obese subjects (body mass index greater than 30 kg/m 2 ) had a 2.29-fold (95% confidence interval (CI): 1.00-5.23) and 1.54-fold (CI: 1.05-2.26) increased risk of late AMD and pigmentary abnormalities in comparison with lean subjects. Finally, the risk of soft drusen was decreased in those subjects with a history of cardiovascular disease (odds-ratio (OR) = 0.72, CI: 0.54-0.97), and increased with increasing levels of HDL-cholesterol (OR = 1.52, CI: 1.14-2.02). None of these results were modified by further adjustments for smoking, educational level and plasma alpha-tocopherol. These results need to be confirmed by other studies, which ideally should be longitudinal and prospective.
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