[Comorbidities of COPD]. / Les comorbidités dans la BPCO.

COPD is a slowly progressive chronic respiratory disease causing an irreversible decrease in air flow. The main cause is smoking, which provokes inflammatory phenomena in the respiratory tract. COPD is a serious public health issue, causing high morbidity, mortality and disability. Related comorbidities are linked to ageing, common risk factors and genetic predispositions. A combination of comorbidities increases healthcare costs. For instance, patients with more than two comorbidities represent a quarter of all COPD sufferers but account for half the related health costs. Our review describes different comorbidities and their impact on the COPD prognosis. The comorbidities include: cardiovascular diseases, osteoporosis, denutrition, obesity, ageing, anemia, sleeping disorders, diabetes, metabolic syndrome, anxiety-depression and lung cancer. The prognosis worsens with one or more comorbidities. Clinicians are faced with the challenge of finding practical and appropriate ways of treating these comorbidities, and there is increasing interest in developing a global, multidisciplinary approach to management. Managing this chronic disease should be based on a holistic, patient-centred approach and smoking cessation remains the key factor in the care of COPD patients.

Constipation associated with brumation? Intestinal obstruction caused by a fecalith in a wild red diamond rattlesnake (Crotalus ruber).

This report describes the fecalith-induced intestinal obstruction of a free-ranging red diamond rattlesnake (Crotalus ruber) and the snake's subsequent history following surgical removal of the fecalith. The captured snake exhibited an abnormally distended abdomen and an extremely hard mass, detected via palpation, near its vent. Coeliotomy yielded a 2.5-cm, 5-g fecalith from the large intestine. Microscopic dissection of the fecalith revealed no evidence of gastrointestinal parasitic worms. Subsequently, we implanted a radio-transmitter that allowed us to track the snake's movements for 7 months (until the radio signal vanished), indicating normal behaviour, complete recovery and good health apart from the obstruction. This observation suggests that fecalith development and intestinal obstruction represent potential risks of long-term faecal retention, an unusual physiological trait well documented among rattlesnakes and other stout, heavy-bodied terrestrial viperid snakes. Dehydration and decreased gut motility associated with brumation (≈hibernation) may predispose temperate snakes to fecalith formation. Regional drought and a small mammal diet with indigestible hairs might have also promoted fecalith formation in this specimen.

Analysis of the relationship between interictal electrical source imaging and PET hypometabolism.

The aim of this paper is to compare interictal EEG source localizations with statistical analysis of hypometabolisms in PET brain imaging. Both methods are currently used in the pre-surgical evaluation of drug-resistant partial epilepsy, but the relationship between electrical source localizations and hypometabolic areas has not been well defined yet. At the present time, these two methods have been performed on five patients in order to develop a comparative quantitative study with these first results which should be then extended to a larger patient database.

[Practical aspects of the management of patients treated by continuous positive airway pressure]. / Le suivi pratique des patients sous pression positive continue.

The therapeutic follow-up is a decisive factor of the success of a long course treatment by continuous positive airway pressure (CPAP). The effectiveness of this treatment on both symptoms and complications must be regularly verified. Polysomnography with CPAP could be necessary in order to check out the efficacy of this treatment and/or to find an associated diagnosis when symptoms persist, particularly a diurnal drowsiness, which is the main therapeutic target in obstructive sleep apnea syndrome (OSAS). The secondary effects that are likely to compromise the compliance of CPAP treatment must be resolved, particularly the nasal intolerance, which are enhanced by mask leakages and often corrected by using heated humidity with CPAP delivery systems. The efficacy of CPAP on both diurnal drowsiness and hypertension is related to the compliance of this treatment which must be regularly verified, at the same time that the clinical evaluation. The data obtained from the device's memory give information concerning the number of hours day to day, in which the CPAP device was running at the prescribed pressure. The first months with CPAP are decisive to avoid a failure of the treatment at long term. This period must be closely monitored by both the physician and the home care provider. Patients should use the CPAP at least 3-4 h by night and all possible means should be used to obtain a maximal compliance. Therapeutic educational programs could help to reach this goal.

[Transition from pediatric to adult care: experience of a cystic fibrosis care center]. / Passage de l'enfant à l'adulte: l'exemple d'un centre de ressources et de compétences pour la mucoviscidose.

BACKGROUND AND OBJECTIVE: Even though patients with cystic fibrosis (CF) are continuously improving their life expectancy, guidelines for transition to adult services have not been clearly determined yet. The aim of this study was to analyze the management of this transition in the CF care center of Angers, France. PATIENTS AND METHOD: From their medical files, we analyzed the transfer of 22 patients with CF from pediatric to adult care. The perceptions of patients and caregivers regarding this transition were evaluated using anonymous questionnaires. RESULTS: The initial objective was to transfer patients around 18 years of age, offering them 3 or 4 joint consultations with a pediatrician and adult lung specialist. The median age of transfer was 22 years and the median duration of the transition period was 9 months. Half of the patients had only 1 joint transfer consultation during transition. The patient reaching the age of 18 and maturity were the most common criteria mentioned for transfer. All highlighted problems leaving the pediatric team they had grown attached to and its familiar environment. Caregivers described the transfer as a success, whereas half of the patients were dissatisfied with it, with both patients and caregivers indicating that the transition was too short without enough joint consultations. CONCLUSIONS: This study shows that this period is a major life event for the patient with CF. The transition process must be organized with the patient and independent behaviors should be encouraged. Adult and pediatric teams need to cooperate. Based on this experience and former medical data, we suggest a transition program for patients with CF.

Influence of toxic endophyte-infected fescue on sperm characteristics and endocrine factors of yearling Brahman-influenced bulls.

Sixteen (mean age = 1.1 +/- 0.1 yr; mean BW = 478 +/- 34 kg) Brahman-influenced bulls were used to determine the influence of fescue type on sperm characteristics and serum concentrations of prolactin, cortisol, and testosterone. Bulls were blocked by BW, scrotal circumference (SC), and pregrazing sperm characteristics and randomly assigned to graze toxic endophyte-infected (EI; 4 bulls/pasture; 2 pastures) or novel endophyte-infected (NE; 4 bulls/pasture; 2 pastures) tall fescue for 121 d. Semen was collected by electroejaculation, and SC was measured and blood samples collected monthly. Sperm were evaluated for motility and morphology with an integrated visual optical system. Overall mean concentration of prolactin was decreased more (P < 0.01) in EI bulls than NE bulls from May to August. Scrotal circumference was not affected by fescue type (P = 0.58); overall SC averaged 36.7 +/- 2.3 cm. Percentage of live sperm was not different (P = 0.24) between NE bulls (80%) than EI bulls (67%) in July and August. Bulls grazing NE fescue had more (P < 0.06) motile sperm than EI bulls in July and August. Percentages of progressive (57 vs. 38%, NE and EI, respectively; P < 0.06) and rapid (67 vs. 46%, NE and EI, respectively; P = 0.04) sperm were greater from bulls grazing NE than EI bulls in July and August. Average velocity of the smoothed sperm path and progressive velocity in a straight line from the beginning to the end of the sperm track were slower (P < 0.09) in EI bulls than NE bulls and were slower (P = 0.04) in August compared with July. Mean width of head oscillation as the sperm swims was less (P < 0.06) in August than July. Concentrations of cortisol and testosterone were not (P > 0.10) influenced by fescue type. Semen from bulls grazing EI had reduced motility and morphology than bulls grazing NE. Detrimental effects of toxic fescue may not be mediated by cortisol, testosterone, or both. Semen quality of bulls grazing toxic EI tall fescue was decreased with increased maximum ambient temperatures.

[Drug-induced pneumonitis in a patient treated with venlafaxine and propanolol]. / Pneumopathie médicamenteuse sous traitement par venlafaxine et propranolol.

INTRODUCTION: Venlafaxine and propranolol have rarely been identified as causes of pulmonary pathology. We describe a case of drug-induced pneumonitis occurring in a patient treated with these two medications. CASE REPORT: A 55 years old woman with liver cirrhosis treated with venlafaxine for 1 year and propranolol for 1 month was admitted to the intensive care unit because of acute respiratory failure. A Mycoplasma pneumoniae pneumonitis was diagnosed. After initial improvement under antibiotics, a new deterioration of respiratory status was observed 4 days after the reintroduction of venlafaxine and propranolol. Spontaneous recovery occurred after these treatments were withheld. Co administration of venlafaxine and propranolol, 2 drugs with affinity for the same cytochrome P450 isoenzyme (CYP2D6), may have contributed to drug accumulation and pulmonary toxicity. The liver cirrhosis of our patient may also have contributed to decreased cytochrome P450 enzymatic activity. CONCLUSIONS: Venlafaxine and propranolol share the same metabolic pathway and their co-administration may be complicated by drug induced pneumonitis.

[Long term use of nCPAP therapy in sleep apnoea patients]. / Acceptation a long terme du traitement par pression positive continue.

INTRODUCTION: Although obstructive sleep apnoea syndrome (OSAS) is usually a lifelong condition, little is known about compliance with nasal continuous positive airway pressure (nCPAP) over longer periods of follow up. METHODS: Long term acceptance of nCPAP was evaluated retrospectively using a survival analysis in 137 consecutive patients who started nCPAP therapy for OSAS between 1985 and 1993. RESULTS: During a mean follow-up of 9.2 +/- 4.7 years, 30 patients died, 5 were lost of follow-up and 30 patients stopped their treatment most of them during the first 5 years. In compliant patients, the median value of daily nCPAP use was 7.5 hours. Kaplan Meier analysis showed that 82% of patients were still using nCPAP at 5 years, 77% at 10 years and 61% at 15 years. Multivariate analysis showed that OSAS severity was an independent predictor of long-term nCPAP use. The rate of nCPAP acceptance at 10 years was 82% in patients with an apnoea-hypopnoea index (AHI) > or = 30 compared to 58% in patients with AHI < 30. CONCLUSION: nCPAP is a suitable long-term therapy for OSAS, particularly in patients with more severe disease, with more than 80% of patients continuing to be compliant with treatment at 10 years.

Economic arguments for the immediate management of moderate-to-severe obstructive sleep apnoea syndrome.

The objective of this study was to measure the impact of a 6-month delay in the diagnosis and treatment of patients with moderate obstructive sleep apnoea syndrome (OSAS) (apnoea/hypopnoea index (AHI) < 30) or severe OSAS (AHI > or = 30) on daytime sleepiness, cognitive functions, quality of life and healthcare expenditure (hospitalisations, medical visits, complementary tests, biological tests and drug prescriptions). In addition, this study aimed to analyse the incremental cost effectiveness ratios related to daytime sleepiness or quality of life following immediate introduction of treatment in these two populations. This study was conducted as a multicentre randomised controlled trial and carried out at two teaching hospitals in France. A total of 171 patients were followed for 6 months, with 82 patients randomised to group 1 "immediate polysomnography" and 89 in group 2 "polysomnography within 6 months". Patients with severe OSAS were deprived of a significant improvement of their daytime sleepiness (5.1 +/- 5.0 at the Epworth Sleepiness Scale score in group 1 versus 0.2 +/- 3.4 in group 2) and quality of life (12.4 +/- 13.3 at the Nottingham Health Profile score in group 1 versus 0.7 +/- 10.1 in group 2) during the waiting time. The impact of delayed management in subjects with less severe OSAS only concerned daytime sleepiness (1.1 +/- 3.3 in group 1 versus 0.3 +/- 4.3 in group 2). Delayed treatment did not affect cognitive functions or healthcare expenditure regardless of the severity of the disease. Incremental cost effectiveness ratios related to rapid introduction of treatment were significantly lower in the patients with more severe OSAS. These results provide fairly clear medical and economic arguments in favour of early management of patients with more severe forms of obstructive sleep apnoea syndrome.

Impaired glucose-insulin metabolism in males with obstructive sleep apnoea syndrome.

The aim of this cross-sectional study was to evaluate the frequency of type-2 diabetes and impaired glucose tolerance (IGT) in a large clinic-based male population presenting various degrees of obstructive sleep apnoea syndrome (OSAS) and to analyse the relationship between OSAS and glucose-insulin metabolism. Male patients (n=595) with suspected OSAS underwent both nocturnal polysomnography and a 2-h oral glucose-tolerance test with measurements of fasting and postload blood glucose and plasma insulin. Insulin sensitivity was evaluated by the ratio of fasting glucose to fasting insulin. OSAS was diagnosed in 494 patients, while 101 patients were nonapnoeic snorers. Type-2 diabetes was present in 30.1% of OSAS patients and 13.9% of nonapnoeic snorers. IGT was diagnosed in 20.0% of OSAS patients and 13.9% of nonapnoeic snorers. Fasting and postload blood glucose increased with severity of sleep apnoea. Insulin sensitivity decreased with increasing severity of sleep apnoea. In addition to body mass index and age, the apnoea/hypopnoea index independently influenced postload blood glucose and insulin sensitivity. The authors conclude that in a clinic-based sample of patients, obstructive sleep apnoea syndrome is associated with a high frequency of type-2 diabetes and impaired glucose tolerance. The relationship between sleep-disordered breathing and impaired glucose-insulin metabolism is independent of obesity and age.

The making of a supermodel.

This model serves as a mechanism for improved care delivery and ensures consistent patient care experience at each affiliate.

A computational role for dopamine delivery in human decision-making.

Recent work suggests that fluctuations in dopamine delivery at target structures represent an evaluation of future events that can be used to direct learning and decision-making. To examine the behavioral consequences of this interpretation, we gave simple decision-making tasks to 66 human subjects and to a network based on a predictive model of mesencephalic dopamine systems. The human subjects displayed behavior similar to the network behavior in terms of choice allocation and the character of deliberation times. The agreement between human and model performances suggests a direct relationship between biases in human decision strategies and fluctuating dopamine delivery. We also show that the model offers a new interpretation of deficits that result when dopamine levels are increased or decreased through disease or pharmacological interventions. The bottom-up approach presented here also suggests that a variety of behavioral strategies may result from the expression of relatively simple neural mechanisms in different behavioral contexts.

Determination of SK&F 108566 (Teveten) in human plasma by reversed-phase high-performance liquid chromatography.

A sensitive, selective and rugged analytical method was developed for the determination of SK&F 108566 (eprosartan, Teveten) in human plasma. The new method employs a simple solid-phase extraction procedure to isolate the drug and its internal standard (SB-200062) from plasma samples. The assay is based on analysis by reversed-phase high-performance liquid chromatography with ultraviolet absorbance detection. The dynamic range of the assay is from 10.0 to 5000 ng/ml, based on 0.5-ml aliquots of plasma. No interference from the endogenous components of plasma, the anticoagulant, or sample collection devices have been noted. The assay has been fully validated. The mean within-run precision (6.5%), between-run precision (4.0%), accuracy (106%) and recovery (71.8%) of the method were considered acceptable. Additionally, SK&F 108566 was found to be stable in plasma under the storage and sample preparation conditions used. This assay has been successfully employed to provide pharmacokinetic data from clinical trials.

Disruption and sequence identification of 2,000 genes in mouse embryonic stem cells.

The dramatic increase in sequence information in the form of expressed sequence tags (ESTs) and genomic sequence has created a 'gene function gap' with the identification of new genes far outpacing the rate at which their function can be identified. The ability to create mutations in embryonic stem (ES) cells on a large scale by tagged random mutagenesis provides a powerful approach for determining gene function in a mammalian system; this approach is well established in lower organisms. Here we describe a high-throughput mutagenesis method based on gene trapping that allows the automated identification of sequence tags from the mutated genes. This method traps and mutates genes regardless of their expression status in ES cells. To facilitate the study of gene function on a large scale, we are using these techniques to create a library of ES cells called Omnibank, from which sequence-tagged mutations in 2,000 genes are described.