Experimental Neurology By Prof Paul Glees Pp xii + 532 (Oxford: Clarendon Press; London: Oxford University Press, 1961) 75s net

The Nervous System

The prevalence of obstructive sleep apnea (OSA) defined at an apnea-hypopnea index (AHI) ≥5 was a mean of 22% (range, 9-37%) in men and 17% (range, 4-50%) in women in eleven published epidemiological studies published between 1993 and 2013. OSA with excessive daytime sleepiness occurred in 6% (range, 3-18%) of men and in 4% (range, 1-17%) of women. The prevalence increased with time and OSA was reported in 37% of men and in 50% of women in studies from 2008 and 2013 respectively. OSA is more prevalent in men than in women and increases with age and obesity. Smoking and alcohol consumption are also suggested as risk factors, but the results are conflicting. Excessive daytime sleepiness is suggested as the most important symptom of OSA, but only a fraction of subjects with AHI >5 report daytime sleepiness and one study did not find any relationship between daytime sleepiness and sleep apnea in women. Stroke and hypertension and coronary artery disease are associated with sleep apnea. Cross-sectional studies indicate an association between OSA and diabetes mellitus. Patients younger than 70 years run an increased risk of early death if they suffer from OSA. It is concluded that OSA is highly prevalent in the population. It is related to age and obesity. Only a part of subjects with OSA in the population have symptoms of daytime sleepiness. The prevalence of OSA has increased in epidemiological studies over time. Differences and the increase in prevalence of sleep apnea are probably due to different diagnostic equipment, definitions, study design and characteristics of included subjects including effects of the obesity epidemic. Cardiovascular disease, especially stroke is related to OSA, and subjects under the age of 70 run an increased risk of early death if they suffer from OSA.

/pdf/obstructive-sleep-apnea-is-a-common-disorder-in-the-4vhoq138wo.pdf

Obstructive sleep apnea is a common disorder in the population-a review on the epidemiology of sleep apnea.

This book provides a series of reviews about pathophysiology, treatment, and, especially, diagnostic testing of clinical syndromes of autonomie failure. The book is organized into sections about integration of sympathetic and parasympathetic function, progressive autonomie failure, and syndromes of autonomie failure. Even cursory examination of the table of contents reveals a lack of consensus about the proper classification for the several conditions involving autonomie failure, reflecting our relative ignorance about pathophysiology in this new discipline in neurology. The chapter authors are well-chosen experts, the quality of writing is generally good, and the chapters fit together well. Several typographical errors are annoying or misleading (eg, description of prazosin as an ot-2 adrenoceptor blocker, page 164). The book is a worthwhile compilation for cardiologists, neurologists, endocrinologiste, and internists who evaluate patients with suspected autonomie failure and need to know the relevant diagnostic tests. Medical students, medical residents, and fellows should benefit from

https://jamanetwork.com/HttpHandlers/ArticlePdfHandler.ashx?journal=intemed&articleId=605447&pdfFileName=archinte_145_3_006.pdf

Autonomic Failure: A Textbook of Clinical Disorders of the Autonomic Nervous System

Obstructive sleep apnea and type 2 diabetes: interacting epidemics.

Type 2 diabetes and obstructive sleep apnea (OSA) are diseases with high prevalence and major public health impact. There is evidence that regular snoring and OSA are independently associated with alterations in glucose metabolism. Thus, OSA might be a risk factor for the development of type 2 diabetes. Possible causes might be intermittent hypoxia and sleep fragmentation, which are typical features of OSA. OSA might also be a reason of ineffective treatment of type 2 diabetes. There is further evidence that the treatment of OSA by continuous positive airway pressure (CPAP) therapy might correct metabolic abnormalities in glucose metabolism. It is assumed that this depends on therapy compliance to CPAP. On the other hand, there are also hints in the literature that type 2 diabetes per se might induce sleep apnea, especially in patients with autonomic neuropathy. Pathophysiological considerations open up new insights into that problem. Based on the current scientific data, clinicians have to be aware of the relations between the two diseases, both from the sleep medical and the diabetological point of view. The paper summarizes the most important issues concerning the different associations of OSA and type 2 diabetes.

/pdf/obstructive-sleep-apnea-and-type-2-diabetes-qzqhzo13vm.pdf

Obstructive sleep apnea and type 2 diabetes

The embryonic stem cell test (EST) is a validated in vitro embryotoxicity test; however, as the inhibition of cardiac differentiation alone is used as a differentiation endpoint in the EST, it may not be a useful test to screen embryotoxic chemicals that affect the differentiation of noncardiac tissues. Previously, methylmercury (MeHg), cadmium and arsenic compounds, which are heavy metals that induce developmental neurotoxicity in vivo, were misclassified as nonembryotoxic with the EST. The aim of this study was to improve the EST to correctly screen such developmental neurotoxicants. We developed a neuronal endpoint (Tuj-1 ID50) using flow cytometry analysis of Tuj-1-positive cells to screen developmental neurotoxicants (MeHg, valproic acid, sodium arsenate and sodium arsenite) correctly using an adherent monoculture differentiation method. Using Tuj-1 ID50 in the EST instead of cardiac ID50, all of the tested chemicals were classified as embryotoxic, while the negative controls were correctly classified as nonembryotoxic. To support the validity of Tuj-1 ID50, we compared the results from two experimenters who independently tested MeHg using our modified EST. An additional neuronal endpoint (MAP2 ID50), obtained by analyzing the relative quantity of MAP2 mRNA, was used to classify the same chemicals. There were no significant differences in the three endpoint values of the two experimenters or in the classification results, except for isoniazid. In conclusion, our results indicate that Tuj-1 ID50 can be used as a surrogate endpoint of the traditional EST to screen developmental neurotoxicants correctly and it can also be applied to other chemicals. Copyright © 2011 John Wiley & Sons, Ltd.

Embryotoxicity assessment of developmental neurotoxicants using a neuronal endpoint in the embryonic stem cell test.

Heterocyclic amines (HCAs) are naturally produced during common cooking processes for meats and fish. HCAs are metabolized by various enzymes, including cytochromes P450, N-acetyl transferases, and sulfotransferases, and their bioactivated metabolites are considered to bind to DNA or protein to show carcinogenic effects. More than 20 HCAs have been identified, of which 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is classified as 'reasonably anticipated to be a human carcinogen' to develop cancers in breast, colon and prostate. The purpose of this study was to evaluate human exposure levels of PhIP and to understand the role of genetic polymorphisms of enzymes on PhIP metabolism. Urine samples were collected from subjects (n = 100) before 3-day meat-restricted diets. Subjects consumed grilled chicken, and their blood and urine were collected before and after the administration of the chickens to investigate genetic polymorphisms and PhIP levels. The mean PhIP levels were 4.22 ± 0.12, 0.61 ± 0.19 and 22.64 ± 1.00 pg ml(-1) in urine under normal conditions and before and after chicken administration, respectively. Among 21 Single-nucleotide polymorphisms (SNP) of CYP1A1, CYP1A2, NATs and UGTs investigated in this study, genotypic groups of CYP1A1/T6235C (MSP I) and CYP1A2/-2467delT showed significant differences in PhIP excretion (P < 0.05). These results suggest that genetic polymorphisms might affect PhIP metabolism, which could improve understanding of populations subject to PhIP-derived health risk.

Genetic polymorphisms in metabolism of 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine

Hemoglobin A1c (HbA1c) is an indicator of long-term glycemic control. The purpose of this study was to determine whether habitual snoring is associated with increased HbA1c levels in non-obese and normoglycemic middle-aged men and women. A total of 6981 subjects (3362 men and 3619 women) aged 40–69 years from the Korean Health and Genome Study were examined for the study. Each participant received a comprehensive physical examination as well as a set of questions pertaining to demographic characteristics and snoring frequency. Habitual snoring was defined as a snoring frequency of ≥4 days week−1. After adjusting for age, abdominal obesity, and other confounding covariates, male habitual snorers showed a 1.69-fold excess [95% confidence interval (CI) 1.30–2.19] odds of having a high HbA1c level. Similarly, premenopausal women with habitual snoring had a 2.31 times (95% CI 1.22–4.39) significantly higher odds of having elevated HbA1clevels compared with non-snorers. This association was not found in postmenopausal women. Multivariate analysis revealed that male habitual snorers aged 40–50 had a 2.08-fold excess (95% CI 1.40–3.09) risk of having an elevated HbA1c level. In male habitual snores over 50, the strength of association was attenuated. Our findings based on cross-sectional data support a hypothesis that habitual snoring is associated with impaired glucose tolerance even in non-obese and normoglycemic men and premenopausal women. However, as waist circumference as an index of abdominal obesity (visceral adiposity) in the present study may only partially represent the effect of visceral fat, there may be a residual confounding from visceral obesity in our result. Longitudinal follow-up studies are necessary to confirm the association between sleep-disordered breathing and impaired glucose tolerance and to examine the causal relationship in a healthy population without obesity and diabetes.

Habitual snoring is associated with elevated hemoglobin A1c levels in non-obese middle-aged adults

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Embryotoxicity assessment of developmental neurotoxicants using a neuronal endpoint in the embryonic stem cell test.

Genetic polymorphisms in metabolism of 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine

Habitual snoring is associated with elevated hemoglobin A1c levels in non-obese middle-aged adults