Vagotomy fails to block the satiating effect of food in the stomach

Normal rats and rats with bilateral subdiaphragmatic vagotomy, each equipped with a pyloric noose, ate liquid food after 3-hr food deprivation. When the noose was open, ingested food accumulated in the stomach and entered the intestine in normal fashion. When the noose was closed, ingested food was trapped in the stomach and did not enter the intestine. Normal and vagotomized rats ate the same size meal with the noose closed as they ate with the noose open and all rats displayed a postprandial sequence of satiety behavior that culminated in resting. Thus, vagotomy failed to block the satiating effect of food in the stomach. This result suggests that gastric distension mediated by vagal afferents is not a necessary stimulus for satiety elicited by food in the stomach.     

Contributions of parental alcoholism, prenatal substance exposure, and genetic transmission to child ADHD risk: a female twin study

BACKGROUND: Genetic influences have been shown to play a major role in determining the risk of attention-deficit hyperactivity disorder (ADHD). In addition, prenatal exposure to nicotine and/or alcohol has also been suggested to increase risk of the disorder. Little attention, however, has been directed to investigating the roles of genetic transmission and prenatal exposure simultaneously. METHOD: Diagnostic telephone interview data from parents of Missouri adolescent female twin pairs born during 1975-1985 were analyzed. Logistic regression models were fitted to interview data from a total of 1936 twin pairs (1091 MZ and 845 DZ pairs) to determine the relative contributions of parental smoking and drinking behavior (both during and outside of pregnancy) as risk factors for DSM-IV ADHD. Structural equation models were fitted to determine the extent of residual genetic and environmental influences on ADHD risk while controlling for effects of prenatal and parental predictors on risk. RESULTS: ADHD was more likely to be diagnosed in girls whose mothers or fathers were alcohol dependent, whose mothers reported heavy alcohol use during pregnancy, and in those with low birth weight. Controlling for other risk factors, risk was not significantly increased in those whose mothers smoked during pregnancy. After allowing for effects of prenatal and childhood predictors, 86% of the residual variance in ADHD risk was attributable to genetic effects and 14% to non-shared environmental influences. CONCLUSIONS: Prenatal and parental risk factors may not be important mediators of influences on risk with much of the association between these variables and ADHD appearing to be indirect.     

Evidence for persistence of adenovirus in the tear film a decade following conjunctivitis

Chronic papillary conjunctivitis has been described following adenoviral conjunctivitis. It is unknown however, how long adenovirus is able to persist in the tear film and conjunctiva. To determine if adenovirus persists in the ocular surface following adenoviral conjunctivitis, 304 patients with a history of adenovirus conjunctivitis from whom an adenovirus had been isolated 10 years previously were sent a questionnaire regarding persistent or recurrent symptoms and were invited to attend. Patients were examined and samples of tears and conjunctival cells were collected from both eyes using tear film washes, filter paper, and swabs, the latter for virus isolation. Extracted DNA from the ocular samples was amplified using primers for herpes simplex virus (thymidine kinase) and adenovirus (hexon) genes. Adenovirus amplicons were sequenced and compared to original serotype. Thirty patients attended, 19 of whom had persistent papillary conjunctivitis. Evidence of adenovirus DNA was detected in 17 of 30 patients, 15 of whom also had evidence of a chronic papillary conjunctivitis. Adenovirus DNA was significantly associated with papillary conjunctivitis (P = 0.03). Adenovirus amplicons were successfully sequenced from six patients. Four patients harbored type 3 adenovirus, the same serotype with which they were infected originally 10 years previously. Two patients were infected originally with adenovirus serotype 3 but the current serotype was type 4. Infection of the ocular surface with adenovirus may predispose to the development of a persistent or recurrent conjunctivitis, the presence of which, appears to be associated with evidence of long term persistence of adenovirus DNA.     

Glucose determination in human aqueous humor with Raman spectroscopy

It has been suggested that spectroscopic analysis of the aqueous humor of the eye could be used to indirectly predict blood glucose levels in diabetics noninvasively. We have been investigating this potential using Raman spectroscopy in combination with partial least squares (PLS) analysis. We have determined that glucose at clinically relevant concentrations can be accurately predicted in human aqueous humor in vitro using a PLS model based on artificial aqueous humor. We have further determined that with proper instrument design, the light energy necessary to achieve clinically acceptable prediction of glucose does not damage the retinas of rabbits and can be delivered at powers below internationally acceptable safety limits. Herein we summarize our current results and address our strategies to improve instrument design.     

Asthma deaths during sports: report of a 7-year experience

BACKGROUND: Asthma mortality and the mortality of athletes during sports have been described separately in detail in the medical literature. However, asthma has not been reported as a cause of death in competitive athletes. OBJECTIVE: The object of this study was to raise the awareness of physicians, coaches, trainers, and parents that children and adults can have fatal asthma exacerbations during and immediately after participating in sports. METHODS: The Temple Sports Asthma Research Center identified athletes from 1993 until 2000 who died during or after sporting activity by using the nationwide Burrell's Information Service. Once a possible asthma-related sports death was identified, the autopsy report was requested from the coroner or medical examiner, and an attempt was made to contact the family. Contact with the family was limited to information about the death, medical history, sports involvement, and any medication usage by the person who had died. Secondary sources, including news reports, were used to confirm whether the subject died of asthma during or immediately after a sporting activity. RESULTS: Two hundred sixty-three possible cases were identified. Sixty-one deaths met the criteria for study inclusion. White deaths outnumbered black deaths by 2 to 1. Deaths among male subjects predominated. Most subjects were younger than the age of 20 years, with the most prevalent age group being between 10 to 14 years old. Fifty-one percent (18 of 35) of the competitive athletes had their fatal event while participating in organized sport, 14 in a practice situation and 4 deaths during a game or meet setting. Basketball and track were the 2 most frequent activities performed at the time of the fatal event. CONCLUSION: The subjects who had fatal asthma exacerbations were usually white male subjects between the ages of 10 and 20 years. Mild intermittent or persistent asthma by history was commonly identified. Sudden fatal asthma exacerbations occur in both competitive and recreational athletes and can be precipitated by sporting activity.     

Enduring effects of prenatal cocaine exposure on selective attention and reactivity to errors: evidence from an animal model

Adult Long-Evans rats, exposed prenatally to 1 of 4 doses of cocaine (0.0,0.5,1.0, or 3.0 mg/kg iv), were tested on a 3-choice visual attention task with an olfactory distractor presented unpredictably on one third of the trials. The performance of all 3 cocaine-exposed groups was significantly more disrupted than that of controls by the presentation of distractors. Results demonstrate that prenatal cocaine exposure increases susceptibility to distractors, using a task specifically designed to measure this function. In addition, the present study revealed that individuals exposed to cocaine in utero exhibit greater performance disruption after an error than controls, in certain types of tasks. Both areas of dysfunction, impaired selective attention and impaired arousal regulation, have important functional consequences in humans, possibly affecting the school performance and social development of cocaine-exposed children.     

TAP genes and immunity

The transporter associated with antigen processing (TAP) is a member of the ATP-binding cassette transporter family that specializes in delivering cytosolic peptides to class I molecules in the endoplasmic reticulum. The TAP is a major target of genetic alteration in tumours and disruption by viral inhibitors. In some species, TAP genes have co-evolved with MHC class I molecules to deliver peptides that are customised for particular alleles. In humans, MHC class I polymorphism determines the level of tapasin-mediated association with TAP and subsequent peptide optimisation within the peptide-loading complex (PLC). MHC class I molecules that still load peptides without complexing to the TAP might be more resistant to viral interference of the PLC and less sensitive to competition for TAP by other class I allotypes.     

Ethical issues concerning genetic testing and screening in public health

Genetic testing (predictive analysis that determines genetic alterations in individuals for clinical purposes) and screening (programs that identify persons within a subpopulation who may be at a higher risk for a genetic disease or condition) are increasingly utilized to promote and improve the public's health. The proliferate use of genetic testing and screening may improve public health outcomes, but it also implicates significant ethical, legal, and social concerns. Within the context of conflicting ethical values from the individual and public health perspectives, individual values such as informed consent and privacy and discrimination protections must be respected. Legal and ethical attempts to exceptionalize genetic tests and information (as compared to other health information) to protect privacy and prevent discrimination are well intended, but can also be unjust and impractical. Respect for individual ethical rights has limits. Principles of public health ethics justify voluntary genetic testing and screening and sharing of data for population-based health purposes. Thus, individual rights should not always trump the use of genetic tests or screening programs (or information derived therefrom) for legitimate public health purposes.     

Anti-idiotypes to oxidized LDL antibodies in intravenous immunoglobulin preparations--possible immunomodulation of atherosclerosis

OBJECTIVE: The aim of this study was to examine whether intravenous immunoglobulin (IVIg) preparations contain anti-oxLDL and anti-anti-oxLDL antibodies. BACKGROUND: Oxidized low-density lipoprotein (oxLDL) is one of the major players in atherogenesis. IVIg can reduce atherosclerosis in experimental animal models. METHODS: Six commercial IVIg preparations were tested for the presence of anti-oxLDL antibodies by EIA. Inhibition studies were performed with the different IVIg preparations and IgGs purified from a pool of sera from patients with high anti-oxLDL antibody levels. Absorption assays were carried out to evaluate the presence of anti-idiotypes against anti-oxLDL antibodies in IVIg preparations. RESULTS: IVIg preparations tested had various degrees of reactivity towards oxLDL. Absorption experiments suggested that the reactivity was specific because it could be effectively absorbed by oxLDL and not by an irrelevant antigen PPD. The reactivity was smaller than that observed with the IgG from the pool with high anti-oxLDL antibody levels. Inhibition studies with IVIg demonstrated 20-45% inhibition of anti-oxLDL binding to oxLDL, compared to 76% inhibition by the pool with high anti-oxLDL levels. To investigate the presence of anti-idiotypes against anti-oxLDL antibodies within IVIg, F(ab')2 fragments of IVIg IgG were used to absorb IgG F(ab')2 fragments from the pool of sera with high anti-oxLDL levels. The decreased binding to oxLDL of the absorbed supernatants shows that IgG F(ab')2 fragments of the IVIg preparations had high inhibitory capacities ranging from 65 to 90%. CONCLUSIONS: IVIg preparations contain both anti-oxLDL and anti-anti-oxLDL activity. This finding may explain the immunomodulating effect of IVIg in atherosclerosis.     

Conventional tube agglutination with polyethylene glycol versus Red Cell Affinity Column Technology (ReACT): a comparison of antibody detection methods

A procedure for antibody detection and identification that utilizes affinity microcolumns to isolate IgG antibodies in a gel matrix containing Protein G and Protein A was commercially available in recent years. We evaluated this method (ReACT, Red Cell Affinity Column Technology, Immucor Co., Norcross, GA) as an alternative to standard tube agglutination testing, in an effort to minimize subjectivity and increase consistency of antibody identification in our hospital blood banks. Although the ReACT kit was withdrawn from the market soon after completion of our study, the advantages and limitations of the procedure warrant consideration should a similar product be reintroduced. The performance of the ReACT method was compared to conventional antibody detection by a standard tube agglutination technique that uses polyethylene glycol (PEG) potentiator (Dominion Biologicals Ltd., Dartmouth, Nova Scotia, Canada). Of 685 serum or plasma samples that were screened for antibodies, 96 samples were found by the PEG procedure to contain clinically significant (n = 70) and insignificant antibodies (n = 26). In contrast, 48 of the samples were found by the ReACT procedure to contain clinically significant (n = 39) and clinically insignificant antibodies (n = 9). For the ReACT method, the sensitivity was 48.8% (95% CI = 37.8%, 58.0%) and the specificity was 99.6% (95% CI = 97.5%, 99.9%), compared to the PEG procedure. While the ReACT microcolumn system was designed to limit detection of clinically insignificant antibodies, this study documents a loss of sensitivity for detection of clinically significant antibodies.