Reflections on the place of polygraphic recordings in the study of hypnotic drugs

Polygraphic recordings are important for studying a new hypnotic molecule. Night recordings are used in the assessment of the objective hypnotic effect over short and long-term periods. They show sleep architecture modifications caused by the hypnotic drug and quantify rebound insomnia following abrupt withdrawal. The comparative usefulness of sleep laboratory recordings and ambulatory monitoring is discussed. Polygraphic recordings also allow to evaluate diurnal residual effect upon vigilance. Twenty-four-hour recordings as well as multiple sleep latency test (MSLT) are used.     

Quinine overdose: review of toxicity and treatment

Quinine sulfate is a commonly prescribed remedy for idiopathic nocturnal leg cramps and is now available "over the counter." A 24-year-old man ingested 8 g (a commonly dispensed quantity) of quinine sulfate in a suicide attempt. Despite hemoperfusion begun 10 h after ingestion, the patient died. This report reviews the toxic manifestations of quinine and the currently available modes of treatment.     

Head and Facial Injuries in Interscholastic Women's Lacrosse

The Purpose of this study was to determine the advisability of protective headgear for interscholastic women playing lacrosse by recording the occurrence of head and facial injuries. During this 3-year study, the head and facial region was the most frequently injured individual area (5.4/100 athletes) of all body structures. The three areas of the head and face that were injured the most were: the head (36%), the eye (23%), and the nose (18%). Being struck by an opponent's stick or the ball were the two most common mechanisms of injury, with contusions (63%), lacerations (14%), and concussions (10%) being the most frequent injuries. Athletes were most often in the act of catching the ball or being stick-checked when the injury occurred to the head and facial area. Twice as many head and facial injuries occurred during game play than practice, with on-goal and midfield play being the most hazardous situations. Over the 3-year study, 75% of the athletes who sustained a head or facial injury were incapacitated for 0 to 1 day. Due to the lack of severity of injuries, we concluded that helmets were not necessary for interscholastic women.     

The V599E BRAF mutation is uncommon in biliary tract cancers.

Activating point mutations of the BRAF oncogene have been identified in several solid tumors, most commonly in cutaneous melanomas and papillary carcinomas of the thyroid. A specific point mutation--V599E--accounts for the overwhelming majority of these mutational events. We explored the frequency of the V599E BRAF mutation in biliary tract cancers. In all, 62 archival biliary tract cancers, including 15 gallbladder cancers, 15 extrahepatic, and 10 intrahepatic cholangiocarcinomas from the United States, and 22 gallbladder carcinomas from Chile were analyzed for the V599E mutation of the BRAF gene using three distinct methods: direct sequencing, a primer extension method (Mutector assay), and the highly sensitive quantitative Gap Ligase Chain Reaction. The common V599E mutation was not identified in any of the 62 biliary cancer samples using these three methods of detection. The V599E somatic mutation of the BRAF gene is absent in biliary tract cancers, at least in the two geographic populations (United States and Chile) examined. Activation of the RAS/RAF/MAP kinase pathway in biliary tract cancers is likely to be secondary to oncogenic RAS mutations, or due to mutations of the BRAF gene at nucleotide positions not explored in the current study.     

Digital peer‐to‐peer information seeking and sharing: Opportunities for education and collaboration in newborn screening

Parents use the internet to connect with their peers and access information about a multitude of health topics, including newborn screening (NBS). As the NBS system evolves, education about NBS must be evaluated and updated to remain accessible and beneficial to parents. In this article, we aim to describe parents' current NBS educational needs and highlight areas to improve newborn screening education by detailing an analysis of NBS posts on an online parenting discussion platform. We analyzed a total of 317 discussion posts on BabyCenter®, finding that parents had questions about and desired support around many aspects of NBS including processes, results, and follow‐up. As a result of this analysis, three recommendations to improve NBS education were developed. Through collaboration and by leveraging technology, we can provide parents with accessible, timely, and desired NBS informational and social support.     

The Association of Teachers of Preventive Medicine's recommendations for postgraduate education in prevention

The Guide to Clinical Preventive Services, prepared in 1989 by the U.S. Preventive Services Task Force, assesses the effectiveness of 169 types of preventive interventions. In 1990, the Association of Teachers of Preventive Medicine formed a panel to review the guide and recommend ways it could be used to enhance both undergraduate and postgraduate medical education. This paper outlines the panel's recommendations of the types of knowledge and attitudes on which postgraduate medical education in prevention should be built. Detailed recommendations are presented, based on the summary findings of the guide, for residency education in prevention. Implementation of these recommendations will integrate preventive services into the continuum of medical care. These recommendations are presented to achieve the goal of educating physicians to approach the total patient, putting the patient's health rather than the disease process in the forefront of primary medical care.     

Metformin during pregnancy reduces insulin, insulin resistance, insulin secretion, weight, testosterone and development of gestational diabetes: prospective longitudinal assessment of women with polycystic ovary syndrome from preconception throughout pregnancy

BACKGROUND: In a prospective observational study of 42 pregnancies in 39 Caucasian women (age 30 +/- 4 years) with polycystic ovary syndrome (PCOS), we examined effects of metformin on maternal insulin, insulin resistance (IR), insulin secretion (IS), weight gain, development of gestational diabetes (GD), testosterone and plasminogen activator inhibitor activity. We assessed the hypothesis that diet-metformin (MET) lessens the physiological gestational increase in IR and reduces gestational weight gain, thus reducing GD. METHODS: Preconception, in an out-patient clinical research centre, MET 1.5 (eight pregnancies) to 2.55 g/day (34 pregnancies) was started. Women with body mass index <25 or >or=25 kg/m(2) were given a 2000 or 1500 calorie/day, high-protein (26% of calories), low-carbohydrate (44%) diet. Calorie restrictions were dropped after conception. RESULTS: On MET, GD developed in three out of 42 pregnancies (7.1%). Median entry weight (94.5 kg) fell to 82.7 on MET at the last preconception visit (P = 0.0001), fell further to 81.6 during the first trimester, was 83.6 in the second trimester, and 89.1 kg in the third trimester. Median weight gain during pregnancy was 3.5 kg. The median percentage reduction in serum insulin was 40% on MET at the last preconception visit; insulin did not increase in the first or second trimesters (P > 0.05), and rose 10% in the third trimester. The median percentage reduction in HOMA IR was 46% on MET at the last preconception visit; IR did not increase (P > 0.05) in the first, second or third trimesters. HOMA insulin secretion fell 45% on MET at the last preconception visit, did not increase in the first trimester, rose 24% in the second trimester, and rose 109% in the third trimester. Testosterone fell 30% on MET at the last preconception visit (P = 0.01) and then rose 74, 61 and 95% during trimesters 1, 2 and 3; median testosterone during the third trimester did not differ from pre-treatment levels. CONCLUSIONS: By reducing preconception weight, insulin, IR, insulin secretion and testosterone, and by maintaining these insulin-sensitizing effects throughout pregnancy, MET-diet reduces the likelihood of developing GD, and prevents androgen excess for the fetus.     

Screening for cognitive impairment in the elderly using the mini-mental state examination

The use by non-medical staff of a brief screening instrument (the mini-mental state examination) to detect cognitive impairment among the elderly in primary care is described. Patients aged 75 years and over registered with nine general practices in north and north west London were invited by their general practitioners to take part in the study and 1170 patients participated, a response rate of 90%. The prevalence of possible or probable cognitive impairment (score below 25 on the mini-mental state examination) was 12.8%. Six per cent of patients scored below 19, at which score a high probability of dementia exists, although less than a third of this group had a diagnosis of dementia in their medical records. There was no significant difference between men and women or by social class in the proportion of patients with low scores, but the proportion with dementia rose from 2.5% in those aged 75-79 years to 29.0% among those aged 90 years and over. Under the new general practitioner contract there is a requirement to provide annual services to the elderly, including a 'mental assessment'. In a practice with a list size of 2000 around 130 patients are likely to be aged 75 years and over. Of these around 17 would require further assessment for possible dementia on the basis of results obtained using the mini-mental state examination.     

Grandparental genotyping enhances exome variant interpretation

Trio exome sequencing is a powerful tool in the molecular investigation of monogenic disorders and provides an incremental diagnostic yield over proband‐only sequencing, mainly due to the rapid identification of de novo disease‐causing variants. However, heterozygous variants inherited from unaffected parents may be inadvertently dismissed, although multiple explanations are available for such scenarios including mosaicism in the parent, incomplete penetrance, imprinting, or skewed X‐inactivation. We report three probands, in which a pathogenic or likely pathogenic variant was identified upon exome sequencing, yet was inherited from an unaffected parent. Segregation of the variants (in NOTCH1, PHF6, and SOX10) in the grandparent generation revealed that the variant was de novo in each case. Additionally, one proband had skewed X‐inactivation. We discuss the possible genetic mechanism in each case, and urge caution in data interpretation of exome sequencing data. We illustrate the utility of expanding segregation studies to the grandparent generation and demonstrate the impact on exome interpretation strategies, by showing that objective genotype data can overcome subjective parental report of lack of symptoms.     

Preliminary findings in the evaluation of hepatic malignancies by radioimmunodetection,X-ray computed tomography,and magnetic resonance imaging

In 12 consecutive patients with suspected metastatic carcinoma of the liver, we evaluated the sensitivity of radiolabeled antibodies to tumor antigens, magnetic resonance imaging, and X-ray computed tomography imaging in the detection of hepatic malignancies. Studies were performed with ¹³¹I labeled antibodies to CEA and/or CSAp; polyclonal, monoclonal and F(ab)₂ antibodies were used. Nontarget radioactivity was diminished by administration of ^99mTc reagents simulating nontumor distribution and use of a computer substraction method. In nine patients with confirmed liver neoplasms, radioimunodetection disclosed the foci of hepatic malignancies. In three patients with suspected liver neoplasms, the antibody studies were positive, but at this time have not been confirmed. X-ray computed tomography each disclosed mass lesions in five patients and magnetic resonance in three. These findings suggest that radioimmunodetection provides greater accuracy in the detection and localization of cancer than other diagnostic modalities currently used.This research was supported in part by NIH Grants CA37408, CA37409, CA37412, and CA39841