Management of albinism: French guidelines for diagnosis and care.

Albinism is a worldwide genetic disorder caused by mutations in at least 20 genes, identified to date, that affect melanin production or transport in the skin, hair and eyes. Patients present with variable degrees of diffuse muco-cutaneous and adnexal hypopigmentation, as well as ocular features including nystagmus, misrouting of optic nerves and foveal hypoplasia. Less often, albinism is associated with blood, immunological, pulmonary, digestive and/or neurological anomalies. Clinical and molecular characterizations are essential in preventing potential complications. Disease-causing mutations remain unknown for about 25% of patients with albinism. These guidelines have been developed for the diagnosis and management of syndromic and non-syndromic forms of albinism, based on a systematic review of the scientific literature. These guidelines comprise clinical and molecular characterization, diagnosis, therapeutic approach and management.

Evaluating Disaster Damages and Operational Status of Health-Care Facilities During the Emergency Response Phase of Hurricane Maria in Puerto Rico.

On September 20, 2017, Hurricane Maria made landfall on Puerto Rico as a category 4 storm, resulting in serious widespread impact across the island, including communication and power outages, water systems impairment, and damage to life-saving infrastructure. In collaboration with the Puerto Rico Department of Health, the Public Health Branch (PHB), operating under the Department of Health and Human Services Incident Response Coordination Team, was tasked with completing assessments of health-care facilities in Puerto Rico to determine infrastructure capabilities and post-hurricane capacity. Additionally, in response to significant data entry and presentation needs, the PHB leadership worked with the Puerto Rico Planning Board to develop and test a new app-based infrastructure capacity assessment tool. Assessments of hospitals were initiated September 28, 2017, and completed November 10, 2017 (n = 64 hospitals, 97%). Assessments of health-care centers were initiated on October 7, 2017, with 186 health-care centers (87%) assessed through November 18, 2017. All hospitals had working communications; however, 9% (n = 17) of health-care centers reported no communication capabilities. For the health-care centers, 114 (61%) reported they were operational but had sustainment needs. In conclusion, health-care facility assessments indicated structural damage issues and operational capacity decreases, while health-care centers reported loss of communication capabilities post-Hurricane Maria.

[Importance of the emotional dimension when providing information to patients with obstructive sleep apnea syndrome]. / Intérêt de la dimension émotionnelle d'une information à destination des patients atteints d'un syndrome d'apnées obstructives du sommeil.

INTRODUCTION: To promote adaptation to treatment with continuous positive airway pressure, an information document was developed for people starting their treatment with continuous positive airway pressure. METHODS: Seven patients with obstructive sleep apnea took part in a focus group. This allowed the identification both of useful information and the best way that this information could be presented. RESULTS: The key specific information objectives and the best emotional register to use were as follows: (1) develop awareness about the physiological mechanisms and consequences that can occur from obstructive sleep apnea syndrome, using formulations arousing fear, (2) enable the recognition of the symptoms, risk factors and chronicity of this syndrome, (3) reassure and motivate the patient about treatment with continuous positive airway pressure. CONCLUSIONS: To promote adaptation to positive airway pressure in early care, combining different emotional tones is preferable, mixing both fear and reassurance.

Expression pattern of synaptic vesicle protein 2 (SV2) isoforms in patients with temporal lobe epilepsy and hippocampal sclerosis.

AIMS: Synaptic vesicle proteins 2 (SV2) are neuronal vesicles membrane glycoproteins that appear as important targets in the treatment of partial and generalized epilepsies. Therefore, we analysed the expression of SV2 isoforms in the hippocampus of patients with temporal lobe epilepsy (TLE). METHODS: SV2A, SV2B and SV2C immunostaining and QuantiGene branched DNA assay were performed on biopsies from 31 consecutive TLE patients with mesial temporal sclerosis (MTS) and compared with 10 autopsy controls. SV2 expression was further compared with Timm's staining, and synaptophysin, Zinc transporter 3 (ZnT3), dynorphin, vesicular glutamate transporter 1 (VGLUT1) and vesicular GABA transporter (VGAT) expression. RESULTS: In TLE patients, SV2A and SV2B expression was decreased in areas of synaptic loss. SV2C, which is weakly expressed or absent in the hippocampus of controls, was overexpressed in 10/11 cases with classical MTS1A and mossy fibre sprouting but not in cases with other types of MTS. SV2C staining was located in the inner molecular layer of the dentate gyrus and colocalized with dynorphin, ZnT3 and VGLUT1, suggesting selective expression in presynaptic glutamatergic Zn(2+) -rich terminals of abnormal sprouting fibres. SV2 expression patterns correlated with histological subtypes of MTS, but not with clinical features or therapeutic regimens in this patient cohort. CONCLUSION: In classical MTS1A, the expression of SV2 isoforms is altered with a marked decrease of SV2A and SV2B paralleling synaptic loss and a selective increase of SV2C in sprouting mossy fibres. These findings suggest a different physiology of sprouting synapses and the possibility to target them with SV2C-specific strategies.

Lung function and airway inflammation monitoring after hematopoietic stem cell transplantation.

BACKGROUND: Induced sputum is a non-invasive method to investigate airway inflammation, which has been used to assess pulmonary inflammatory diseases. However, this procedure has not been studied in the context of hematopoietic stem cell transplantation (HSCT). METHODS: We monitored lung function in 182 patients who underwent HSCT and measured airway inflammation by sputum induction in 80 of them. We prospectively measured FEV1, FVC, DLCO, KCO, TLC, RV, exhaled nitric oxide (FeNO) as well as sputum cell counts before and 3, 6, 12, 24 and 36 months after HSCT. RESULTS: For the whole cohort there was a progressive decrease in TLC, which was significant after 3 years (p < 0.01). By contrast, there was no change in other lung functions parameters or in FeNO. Baseline sputum analysis revealed increased neutrophil counts in patients {Median (IQR): 63% (38-79)} compared to healthy subjects matched for age {Median (IQR): 49% (17-67), p < 0.001} but there was no significant change in any type of sputum cell counts over the three years. When comparing myeloablative (MA) vs non-myeloablative (NMA) conditioning, falls in FEV1, FVC and DLCO, and rise in RV and sputum neutrophils were more pronounced over the first year of observation in those receiving MA. CONCLUSIONS: There was a progressive loss in lung function after HSCT, featuring a restrictive pattern. Myeloablative conditioning was associated with early rise of sputum neutrophils and greater alteration in lung function over the first year.

Wnt1 and BMP2: two factors recruiting multipotent neural crest progenitors isolated from adult bone marrow.

Recent studies have shown that neural crest-derived progenitor cells can be found in diverse mammalian tissues including tissues that were not previously shown to contain neural crest derivatives, such as bone marrow. The identification of those "new" neural crest-derived progenitor cells opens new strategies for developing autologous cell replacement therapies in regenerative medicine. However, their potential use is still a challenge as only few neural crest-derived progenitor cells were found in those new accessible locations. In this study, we developed a protocol, based on wnt1 and BMP2 effects, to enrich neural crest-derived cells from adult bone marrow. Those two factors are known to maintain and stimulate the proliferation of embryonic neural crest stem cells, however, their effects have never been characterized on neural crest cells isolated from adult tissues. Using multiple strategies from microarray to 2D-DIGE proteomic analyses, we characterized those recruited neural crest-derived cells, defining their identity and their differentiating abilities.

Psychological variables as predictors of adherence to treatment by continuous positive airway pressure.

STUDY OBJECTIVES: We examined whether psychological variables enable us to predict adherence to CPAP in order to construct a predictive model to identify patients at risk of abandoning treatment. METHOD: One hundred and twenty-two Obstructive Sleep Apnoea (OSA) patients were studied before and one month after beginning CPAP treatment. All patients completed four psychological evaluation instruments before CPAP treatment: a health perception questionnaire (Nottingham Health Profile: NHP), a mental health rating scale (Hospital Anxiety and Depression Scale: HADS) and two disease-specific questionnaires that measure the patient's understanding of OSA and its treatment (Apnea Knowledge Test: AKT) and his attitudes to OSA and CPAP (Apnea Beliefs Scale: ABS). RESULTS: Thirty percent of the participants were non-adherent at one month. Decision-tree analysis indicated that it was possible to correctly classify 85.7% of non-adherent patients using three baseline factors (Emotional reactions score [NHP], age, and total score on ABS). Logistic regression analyses confirmed these two psychological variables as independent predictors of adherence. CONCLUSION: Assessing psychological well-being and subjective health status at onset of CPAP enables the identification of patients at risk of abandoning CPAP treatment. This subgroup could then be targeted early to receive supportive and educational measures to improve adherence rates.

[An unusual complication of thoracostomy]. / Une complication inhabituelle d'une thoracostomie.

INTRODUCTION: Post pneumonectomy infection is a well-described surgical complication. Treatment usually involves thoracostomy and requires local treatments. We report here an unusual complication of this situation. CASE REPORT: A 62 year old man had a pneumonectomy for non-small cell lung cancer. Following this he required a thoracostomy to treat a thoracic empyema and this was treated with local anti-septic agents. Subsequently he developed asthenia and a diagnosis of hyperthyroidism was made secondary to local disinfectant treatment with iodine agents. CONCLUSIONS: We describe an original case of thyroxicosis occurring in a patient following treatment for post-pneumonectomy empyema. We would recommend monitoring thyroid function in this context.

[Subcutaneous myiasis. A case report]. / Myase sous-cutanée. A propos d'un cas.

UNLABELLED: Although myiasis or hypodermiasis is a parasitic disease that theoretically has practically been eradicated, a new case has recently been reported in Lower Normandy, in a bovine husbandry region. CASE REPORT: A seven-year-old-girl was hospitalized in November 1998 for an edema of variable size on the right eyelid, which was not painful and non-inflammatory, with accompanying ptosis. A number of subcutaneous nodules were found on the forehead above the right eye socket. The right eye itself was unaffected. The symptoms had evolved over a ten-day period. Further examination did not detect any sign of eosinophilia, and the hypodermiasis and toxocariasis serologies were negative. The clinical evolution was characterized by the regression and reappearance of the edema on several occasions, after which the edematous mass became progressively larger, more swollen and painful, so that it was no longer possible to open the eye. The subcutaneous nodules partially disappeared when the edema increased in size. Six weeks after the onset of clinical signs, eosinophilia was observed and the hypodermiasis serology was positive. Due to the limitation of the visual field as a result of the edema, a short-term steroid treatment (seven days) was orally administered. The patient recovered, and no further edematous signs were noted. However, contrary to what had been reported in the literature, the larvae did not appear on the surface of the skin. CONCLUSION: In conclusion, in bovine husbandry regions the diagnosis of hypodermiasis should always be kept in mind in the event of clinical signs indicative of larval migration, even in the initial absence of eosinophilia, and even with an initially negative hypodermiasis serology. This disease should soon be eradicated, as regional bovine treatment programs have been set up to systematically treat the cattle and eliminate the larvae.

Stereochemical aspects of 1,3-butadiene metabolism and toxicity in rat and mouse liver microsomes and freshly isolated rat hepatocytes.

1,3-Butadiene (BD) is a gas used heavily in the rubber and plastics industry. BD and its epoxide metabolites have been shown to be carcinogenic and mutagenic in rodents, and BD has been classified by IARC as a group 2A carcinogen. We have examined the role of stereochemistry in species-dependent metabolism and toxicity of BD. Diastereo- and enantioselective synthetic routes to butadiene monoxide (BMO), butadiene bisoxide (BBO), and 3,4-epoxybutane-1,2-diol isomers have been developed. These routes have allowed the development of chiral gas chromatographic and GC/MS analytical procedures for quantitation of these metabolites in biological experiments. We have utilized hepatic microsomes from male B6C3F1 mice and hepatic microsomes and intact hepatocytes from male Sprague-Dawley rats as experimental systems. At 30 min, BMO production from BD was two times higher in mouse hepatic microsomes than in rats, and stereoselective analysis was used to determine the relative formation of (R)- and (S)-BMO. Formation of BBO from both (R)- and (S)-BMO was characterized in rat and mouse microsomal systems. As expected, more BBO was formed in mouse hepatic microsomes (3-4-fold) than in rat hepatic microsomes. No difference in total BBO formed from either isomer was observed in rat microsomes, but in mouse microsomes significantly more BBO was produced from (S)-BMO than from (R)-BMO. The cytotoxicity of each BMO and BBO enantiomer was examined in freshly isolated rat hepatocytes. (R)-BMO showed greater cytotoxicity than (S)-BMO. Stereospecific cytotoxicity was also observed using BBO enantiomers and (meso)-BBO was more cytotoxic than either the (R:R) or the (S:S)-BBO. The results show that stereochemistry plays an important role in BD metabolism and cytotoxicity and for the purposes of risk assessment needs to be compared across species.

Metabolism of 1,3-butadiene to butadiene monoxide in mouse and human bone marrow cells.

1,3-Butadiene (BD), a gas used in the production of rubber and plastics, induces a high incidence of leukemias and lymphomas in B6C3F1 mice. Because of the potential involvement of the hematopoietic system in response to BD, we have examined metabolism of BD by B6C3F1 mouse and human bone marrow and by purified human myeloperoxidase (MPO), an enzyme rich in bone marrow. BD was metabolized to butadiene monoxide (BMO) by MPO and by mouse and human bone marrow cells. In all of these systems metabolism was stimulated by hydrogen peroxide suggesting a peroxidase-mediated process. In B6C3F1 mouse bone marrow cell lysates, hydrogen peroxide but not NADPH stimulated metabolism suggesting that cytochrome P450 was not involved in BMO formation. Metabolism of BD to BMO in hydrogen peroxide-fortified mouse bone marrow cell lysates was more than two orders of magnitude lower than in either NADPH-fortified rat or mouse hepatic microsomes. Experiments using both mouse and human bone marrow cells showed that cells from both sources could generate BMO from BD. These data show that BD can be converted to BMO in a target organ of BD carcinogenicity.

Solvolytic formation of 1,2-dichloro-3,4-epoxybutane from butadiene monoxide under physiological conditions.

Butadiene monoxide, a presumed carcinogenic metabolite of butadiene, is stable in water or phosphate buffer, but was found to rapidly disappear from the headspace of solutions (10(-6) to 10(-4) M) in phosphate-buffered saline incubated at 37 degrees C. The process was first order with respect to monoxide concentration, with an apparent rate constant of 6.6 x 10(-4) sec-1. Mass spectrometric examination of the major product formed indicated it to be 1,2-dichloro-3,4-epoxybutane, which was confirmed by synthesis. Formation of the dichloro epoxide was linearly dependent on chloride ion concentration of the medium, but independent of dissolved oxygen. The formation of the dichloro epoxide is explained by slow solvolytic formation of a chloronium ion from butadiene monoxide, which is followed by attack of chloride ion to generate chlorine and butadiene. The chlorine is than rapidly trapped by second molecule of butadiene monoxide. This was confirmed by competitive trapping of generated chlorine by inclusion of crotyl alcohol in the incubation. A similar pathway has recently been demonstrated for reversible formation of bromine from solvolytically generated bromonium ions. The facile formation of dichloroepoxybutane under physiological conditions may be of significance in the toxicity of butadiene.