Limb deficiency defects, MSX1, and exposure to tobacco smoke

There is increasing evidence from epidemiologic studies that genetic susceptibilities may modify the teratogenic effects of smoking. A previous study suggested that maternal smoking in the presence of a dinucleotide repeat polymorphism for MSX1 produced an almost fivefold increased risk for limb anomalies, providing evidence for a gene-environment interaction. The current study examined this potential interaction, using case-control data with several methodologic improvements, including a larger sample size and more detailed information on cigarette smoke exposures. Cases (n = 92) were ascertained from pregnancies ending in 1987-1989, and controls (n = 180) were randomly selected from eligible liveborn infants. In telephone interviews, women reported smoking behaviors during the month before pregnancy through the end of the first trimester. Odds ratios (OR) for maternal and paternal smoking ranged from 1.0 to 1.4, risk estimates were imprecise; for example, the OR for maternal smoking >or=20 cigarettes per day, versus none, was 1.3 (95% confidence interval (CI) 0.5-3.4). Relative to the homozygous wildtype, the OR was 1.5 (95% CI 0.7-3.5) for the homozygous variant genotype and 0.8 (95% CI 0.5-1.4) for the heterozygous variant genotype. There was no evidence that maternal smoking or both parents smoking, in combination with a susceptible MSX1 genotype, conferred an additional increase in risk of limb defects. This study did not find a gene-environment interaction between maternal smoking, infant MSX1 CA repeat polymorphism, and risk of limb deficiency defects. This finding contrasts with results of a previous study, which provided initial evidence for such an interaction. Several important methodological differences may have contributed to the differences in findings between the two studies.     

Periconceptional dietary intake of choline and betaine and neural tube defects in offspring

Periconceptional intake of folic acid prevents some neural tube defects (NTDs). Other nutrients may also contribute to NTD etiologies; a likely candidate is choline. Similar to folic acid, choline is involved in one-carbon metabolism for methylation of homocysteine to methionine. The authors investigated whether maternal periconceptional dietary intakes of choline and its metabolite betaine influence NTD risk. Data were derived from a case-control study of fetuses and infants with NTDs among 1989-1991 California births. In-person interviews were conducted with mothers of 424 NTD cases and with mothers of 440 nonmalformed controls. A standard 100-item food frequency questionnaire was used to assess nutrient intake. Dietary intakes of choline were associated with reduced NTD risks. Controlling for intake of supplemental folic acid, dietary folate, dietary methionine, and other covariates did not substantially influence risk estimates for choline. NTD risk estimates were lowest for women whose diets were rich in choline, betaine, and methionine. That is, for women whose intake was above the 75th percentile compared with below the 25th percentile for all three nutrients, the odds ratio was 0.17 (95% confidence interval: 0.04, 0.76). Study findings for dietary components other than folic acid offer additional clues about the complex etiologies of NTDs.     

The cardiovascular safety of high-dose intravenous granisetron in cancer patients receiving highly emetogenic chemotherapy

Objectives To assess the cardiovascular safety, tolerability and efficacy of high doses of granisetron for the treatment of nausea and vomiting in patients undergoing highly emetogenic chemotherapy.Methods Patients with histologically confirmed malignant disease were given an intravenous infusion of granisetron, 160 g/kg, over 30 min, starting 15 min after highly emetogenic chemotherapy. Patients underwent cardiac monitoring for 24 h following the granisetron infusion. Pulse, blood pressure and electrocardiogram (lead II and ambulatory) measurements were taken, and routine clinical chemistry and haematology tests performed. Blood samples for pharmacokinetic analysis were taken before the granisetron infusion, and at intervals afterwards. Adverse events were self-assessed using a symptom checklist. Self-assessment categorical rating scales were used to evaluate patient nausea, vomiting and retching.Results Ten patients (eight females and two males; average age 41.5 years) completed the trial and were included in the safety and efficacy assessments. No clinically relevant changes in electrocardiogram, pulse rate, blood pressure or laboratory parameters were observed. Furthermore, in the 7 days following dosing there were no serious adverse events leading to withdrawal from the trial. A complete response (no vomiting, retching or, at most, mild nausea) was experienced by five patients. Six patients had no, or mild, nausea and an additional two patients vomited on a maximum of two occasions. Additional antiemetic rescue medication was given to three patients during the 24-h trial period. Despite considerable interpatient variability, C_max and AUC parameters were proportionally greater than values reported for lower doses of granisetron.Conclusions Granisetron administered at four times the upper recommended dose demonstrated good efficacy and tolerability with no clinically important cardiac effects.     

Dental erosion in gastroesophageal reflux disease

Dentists are often the first health care professionals to diagnose dental erosion in patients with gastroesophageal reflux disease (GERD). Gastroesophageal reflux (GER) is the passage of gastric contents into the esophagus, and GERD is defined as symptoms or complications of GER. Twenty-four-hour monitoring of esophageal pH is helpful in diagnosing GERD. Treatment of dental erosion resulting from GERD involves a multidisciplinary approach among family physician, dentist, prosthodontist, orthodontist and gastroenterologist. When possible, dental erosion should be treated with minimal intervention, and such treatment should include control of microflora, remineralization, adhesive restorations and use of biomimetic materials.     

Animated PowerPoint as a tool to teach anatomy

Anatomy is a visual science. For centuries, anatomic information has been conveyed through drawings that have been presented to students through every available medium. The projection of animated images from a computer is a medium that offers great promise in effecting improved communication of anatomic information. Using Microsoft PowerPoint software, we have developed animated presentations for all of our lectures in Gross and Developmental Anatomy. As a starting point, we scan pen-and-ink drawings to create a digital image. The image may be edited and manipulated in an image processing program. Next, the image is imported into a PowerPoint slide where it is labeled and otherwise enhanced (arteries overlaid with red color, veins in blue, etc.) and the enhancements are animated, as we describe here step by step. For the lecture, the file is loaded on a server that is accessible through a network from a computer in the lecture hall. The output is directed to a video projector and the PowerPoint presentation is projected in the "Slide Show" mode. We use a wireless mouse that allows us to control the presentation from anywhere in the room. Before the lecture, students are provided with the same unlabeled drawings as handouts, and during the lecture the students are actively engaged in labeling the drawings and making related notes. After the lecture, the file is saved in HTML format and posted on our course web site where students can access the slides. Evaluation by the students at the end of the course demonstrated that this style of presentation was very favorably received.     

Randomized double-blind phase II survival study comparing immunization with the anti-idiotypic monoclonal antibody 105AD7 against placebo in advanced colorectal cancer

The cancer vaccine 105AD7 is an anti-idiotypic monoclonal antibody that mimics the tumour-associated antigen 791T/gp72 (CD55, Decay Accelerating Factor) on colorectal cancer cells. Phase I studies in patients with advanced disease confirmed that 105AD7 is non-toxic, and that T cell responses could be generated. A prospective, randomized, double-blind, placebo-controlled survival study in patients with advanced colorectal cancer was performed. 162 patients were enrolled between April 1994 and October 1996. Patients attended at trial entry, and at 6 and 12 weeks, where they received 105AD7 or placebo. Study groups were comparable in terms of patient demographics, and time from diagnosis of advanced colorectal cancer (277.1 v 278.6 days). Baseline disease was similar, with 50% of patients having malignancy in at least 2 anatomic sites. Compliance with treatment was poor, with only 50% of patients receiving 3 planned vaccinations. Median survival from randomization date was 124 and 184 days in 105AD7 and placebo arms respectively (P = 0.38), and 456 and 486 days from the date of diagnosis of advanced disease (P = 0.82). 105AD7 vaccination does not prolong survival in patients with advanced colorectal cancer. The reasons for lack of efficacy are unclear, but may reflect the high tumour burden in the patient population, and poor compliance with immunization. Further vaccine studies should concentrate on patients with minimal residual disease.     

Forebrain osmotic regulation of the sympathetic nervous system

1. Accumulating evidence in both humans and animals indicates that acute increases in plasma osmolality elevate sympathetic nerve activity (SNA). In addition, plasma hyperosmolality (or hypernatraemia) can produce sustained increases in SNA and arterial blood pressure (ABP) through stimulation of forebrain osmoreceptors. 2. Although an abundance of information exists regarding the osmoregulatory circuits for thirst and secretion of antidiuretic hormone, much less is known about those pathways and synaptic mechanisms linking osmotic perturbations and SNA. To date, the available evidence suggests that osmosensitive sites within the forebrain lamina terminalis, such as the organum vasculosum of the lamina terminalis, are key elements that link plasma hypertonicity to elevated SNA. 3. The major efferent target of osmosensitive regions in the forebrain lamina terminalis is the hypothalamic paraventricular nucleus (PVH). Evidence from a number of studies indicates that the PVH contributes to both acute and chronic osmotically driven increases in SNA. In turn, PVH neurons increase SNA through a direct vasopressinergic spinal pathway and/or a glutamatergic pathway to bulbospinal sympathetic neurons of the rostral ventrolateral medulla. 4. Future studies are needed to: (i) define the contribution of various osmosensitive regions of the forebrain lamina terminalis to acute and chronic osmotically driven increases in SNA; (ii) identify the cellular mechanisms and neural circuitry linking plasma osmolality and SNA; and (iii) define whether such mechanisms contribute to elevated SNA in salt-sensitive hypertension.     

A Combination of Essential Fatty Acids,Panax Ginseng Extract,and Green Tea Catechins Modifies Brain fMRI Signals in Healthy Older Adults

Objectives

To assess the effects of a combination of omega 3 essential fatty acids, green tea catechins, and ginsenosides on cognition and brain functioning in healthy older adults.

Design

Double-blind, placebo-controlled, crossover design randomized controlled trial with 26-day intervention phases and a 30-day washout period.

Setting

The Institute for Dementia Research and Prevention at the Pennington Biomedical Research Center.

Participants

Ten independently-living, cognitively-healthy older adults (mean age: 67.3 + 2.01 years). Intervention: Daily consumption of an investigational product (trade name “Cerbella TM”) consisting of an emulsified liquid combination of standardized fish oil, panax ginseng extract, and green tea catechins in a flavored base of lecithin phospholipids optimized to maximize bioavailability of the active ingredients.

Measurements

Before and after supplementation with the investigational product or placebo, participants completed cognitive tests including the Mini Mental State Exam (MMSE), Stroop test, Digit Symbol Substitution Test (DSST), and Immediate and Delayed Recall tests, as well as functional magnetic resonance imaging (fMRI) during a standard cognitive task switching paradigm.

Results

Performance on the MMSE, Stroop test, and DSST increased significantly over one month of supplementation with the investigational product (one-sample t tests, p<.05) although differences between these changes and corresponding changes during supplementation with placebo were not significant (two-sample t tests, p>.05). During supplementation with the investigational product, brain activation during task performance increased significantly more than during supplementation with placebo in brain regions known to be activated by this task (anterior and posterior cingulate cortex). Functional connectivity during task execution between task regions (middle frontal gyrus and anterior cingulate cortex) increased significantly during supplementation with the investigational product, relative to placebo. Functional connectivity during rest between task regions (precentral gyrus and middle frontal gyrus) and default mode network regions (medial frontal gyrus and precuneus) decreased during supplementation with the investigational product relative to placebo, suggesting greater segregation of task and rest related brain activity.

Conclusion

One-month supplementation with a combination of omega 3 essential fatty acids, green tea catechins, and ginsenosides was associated with suggestive changes in cognitive functioning as well as modification of brain activation and brain functional connectivity in cognitively healthy older adults.

     

European guidelines for workplace drug testing in oral fluid

These guidelines for Legally Defensible Workplace Drug Testing have been prepared and updated by the European Workplace Drug Testing Society (EWDTS). The European Guidelines are designed to establish best practice procedures whilst allowing individual countries to operate within the requirements of national customs and legislation. The EWDTS recommends that all European laboratories that undertake legally defensible workplace drug testing should use these guidelines as a template for accreditation. These guidelines are relevant to laboratory‐based testing only. These guidelines follow current best practices and are constantly under review.     

Marble bone disease: a review of osteopetrosis and its oral health implications for dentists

Osteopetrosis is one cause of osteosclerosis and may result in such serious oral complications as osteomyelitis and exposed necrotic bone. Dentists should be aware of patients with the disease because of its effect on osteoclast function, which results in impaired wound healing. The purpose of this paper is to review the causes, pathogenesis and differential diagnosis of osteopetrosis and to provide guidance to dentists on the management of patients with osteopetrosis.