Dose-dependent effectiveness of acellular pertussis vaccine in infants: A population-based case-control study.

BACKGROUND: Pertussis is a vaccine-preventable disease which is most severe in young infants. More than two decades after the introduction of acelluar pertussis vaccines (aPV) in national immunization programs in many countries worldwide, a resurgence of pertussis has been recognized. Suboptimal effectiveness of aPV has been blamed as one major reason but only few studies have evaluated dose-dependent vaccine effectiveness (VE) provided by aPV in current practice. METHODS: We performed a population-based retrospective case-control study by comparing pertussis immunization data of children 2.5 months to 2 years of age hospitalized for pertussis and residing in Switzerland with immunization data of a random control sample of children aged 2 years and residing in Switzerland. VE was defined as the percentage of hospitalizations avoided by number of aPV doses. It was calculated as 1-infection rate ratio (IRR)*100. IRR was calculated by dividing infection rates of vaccinated children and infection rates of unvaccinated children. To get dose specific VE,infection rates were stratified by number doses received. RESULTS: VE against hospitalization due to pertussis increased significantly with each consecutive aPV dose in a "3 + 1" primary course in infants: 42.1% (95% CI: 11.3-62.6), 83.9% (70.2-92.1), 98.2% (96.1-99.3), and 100% (97.9-100) after the 1st, 2nd, 3rd, and 4th dose, respectively. CONCLUSION: Acellular pertussis vaccines continue to demonstrate protection against hospitalization due to pertussis in infants and young children. Therefore, together with advancing immunization of pregnant women and household contacts, better control of severe pertussis in young infants can be achieved by timely initiation of immunization.

Gastric ghrelin, GOAT, leptin, and leptinR expression as well as peripheral serotonin are dysregulated in humans with obesity.

BACKGROUND: Gastrointestinal hormone release and the regulation of appetite and body weight are thought to be dysbalanced in obesity. However, human data investigating the expression of gastrointestinal hormones in the obese are rare. We studied the expression of ghrelin, leptin, and the serotonergic system in stomach tissue and serum of obese and non-obese individuals. METHODS: Gastric tissue and serum were collected from 29 adult obese (BMI 48.7 ± 10.6 kg/m(2) ; mean ± SD) who underwent laparoscopic sleeve gastrectomy. Gastric biopsies, surgery specimen or serum was obtained from 35 adult non-obese humans (BMI 22.7 ± 1.9 kg/m(2) ). Ghrelin, ghrelin O-acyl transferase (GOAT), leptin, leptin receptor, and tryptophan hydroxylase 1 (TPH1) mRNA expression were measured by qRT-PCR. Serotonin (5HT) and leptin protein concentration were quantified in tissue extracts and serum; GOAT and ghrelin-positive cells were immunohistologically quantified in tissue. Additionally, 21 blood immune markers were analyzed. KEY RESULTS: In gastric tissue, GOAT-positive cells were reduced (p < 0.01), but ghrelin-positive cells and mRNA were increased (both p < 0.05) in obese compared with non-obese individuals. Gastric leptin (p < 0.001) and leptin receptor (p < 0.001) mRNA expression, as well as leptin concentrations in serum (p < 0.001), were increased in obese compared with non-obese individuals. Serum 5HT was reduced (p < 0.05), while tissue 5HT and TPH1 mRNA were reduced only by trend. Interleukin 1 receptor a (IL1Ra), IL-8, IL-12, and monocyte chemoattractant protein 1 (IL1Ra) were increased and IL1Ra correlated negatively with serum leptin. CONCLUSIONS & INFERENCES: Our data indicate that obesity causes a dysregulation of gastrointestinal hormones at the tissue level and serum, including a negative correlation with an increased marker of subclinical inflammation.

Expression and secretion of RANTES (CCL5) in human adipocytes in response to immunological stimuli and hypoxia.

Obesity and related disorders represent states of systemic low-grade inflammation. Chemokine secretion by adipocytes may initiate leukocyte infiltration in obese adipose tissue and thus mediate an important step in the establishment of chronic immune activation. The chemokine RANTES (regulated upon activation normal T cell expressed and secreted)/CCL5 is a chemoattractant for various leukocyte subsets. This study was designed to examine whether RANTES is expressed and released by human adipocytes and how its expression is regulated. RANTES expression under basal conditions was studied in mature adipocytes. Cells were therefore challenged with lipopolysaccharide (LPS), interferon (IFN)-gamma, interleukin (IL)-4, monocyte chemoattractant protein (MCP)-1 or exposed to low oxygen pressure. RANTES was expressed and secreted constitutively in most samples of mature adipocytes from the omental and the subcutaneous depot. RANTES release was dependent on adipocyte size and also seemed to be higher from cells of obese donors. Hypoxia (4% O (2)) caused an approximately 36% increase of RANTES release. Human adipocytes express the chemokine RANTES and are thus identified as a novel cellular source of this immune mediator. LPS and IFNgamma do not seem to play a significant role for the expression of RANTES in contrast to moderate hypoxia, which points to a distinct role in the innate immune system.

Modafinil, d-amphetamine and placebo during 64 hours of sustained mental work. I. Effects on mood, fatigue, cognitive performance and body temperature.

Modafinil is an alerting substance that is considered safer than amphetamine with fewer side effects. Although modafinil has been used successfully to treat narcolepsy, relatively little is known about its ability to ameliorate fatigue and declines in mental performance due to sleep deprivation (SD) in a normal population. Forty-one military subjects received either 300 mg of modafinil, 20 mg of d-amphetamine, or placebo on 3 separate occasions during 64 hours of continuous cognitive work and sleep loss. Three drug treatments were given: at 23.30 hours and 05.30 hours during the first and second SD nights, respectively, and once at 15.30 hours during the third day of continuous work. Subjective estimates of mood, fatigue and sleepiness, as well as objective measures of reaction time, logical reasoning and short-term memory clearly showed better performance with both modafinil and amphetamine relative to placebo. Both modafinil and amphetamine maintained or increased body temperature compared to the natural circadian cycle observed in the placebo group. Also, from subject debriefs at the end of the study, modafinil elicited fewer side-effects than amphetamine, although more than the placebo group. Modafinil appears to be a good alternative to amphetamine for counteracting the debilitating mood and cognitive effects of sleep loss during sustained operations.