bluuebunny/crossref_metadata_2025 huggingface dataset:
Photo-activated Azi-Etomidate, a General Anesthetic Photolabel, Irreversibly Enhances Gating and Desensitization of γ-Aminobutyric Acid Type A Receptors
Authors: Zhong Huijun , Rüsch Dirk , Forman Stuart A.
Published: March 2009

Background

The general anesthetic etomidate acts via gamma-aminobutyric acid type A (GABA(A)) receptors, enhancing activation at low GABA and prolonging deactivation. Azi-etomidate is a photo-reactive etomidate derivative with similar pharmacological actions, which has been used to identify putative binding sites. The authors examine the irreversible effects of azi-etomidate photo-modification on functional GABA(A) receptors in cell membranes.

Methods

GABA(A) receptors (alpha1beta2gamma2L) were expressed in both Xenopus oocytes and human embryonic kidney cells exposed to 365 nm light-activated azi-etomidate with or without GABA, then extensively washed. Receptor-mediated chloride currents were measured using voltage clamp electrophysiology to assess the ratio of peak responses at 10 microm and 1 mm GABA (I10/I1000) and deactivation time course.

Results

After azi-etomidate photo-modification, I10/I1000 ratios were persistently enhanced and deactivation was prolonged, mimicking reversible azi-etomidate actions. Azi-etomidate and ultraviolet light were required to produce irreversible receptor modulation. Adding GABA during photo-modification greatly enhanced irreversible modulation. Azi-etomidate modification also dose-dependently reduced maximal GABA-activated currents, consistent with accumulation of permanently desensitized receptors. Excess etomidate during azi-etomidate photo-modification competitively reduced permanent desensitization. Persistent channel modulation was blocked by 320-fold excess etomidate but enhanced when 32-fold excess etomidate was present.

Conclusions

Azi-etomidate efficiently photo-modifies etomidate sites on GABA(A) receptors in intact cells, producing persistent functional changes that mimic its reversible effects. The results demonstrate sequential modification at more than one etomidate site per receptor. The sites display reciprocal positive cooperativity. In combination with focal photo-activation, azi-etomidate may prove useful for studies of anesthetic actions in neural circuits.
The Effects of Mild Perioperative Hypothermia on Blood Loss and Transfusion Requirement
Authors: Rajagopalan Suman , Mascha Edward , Na Jie , Sessler Daniel I.
Published: March 2009

Background

Anesthetic-induced hypothermia is known to reduce platelet function and impair enzymes of the coagulation cascade. The objective of this meta-analysis and systematic review was to evaluate the hypothesis that mild perioperative hypothermia increases surgical blood loss and transfusion requirement.

Methods

The authors conducted a systematic search of published randomized trials that compared blood loss and/or transfusion requirements in normothermic and mildly hypothermic (34-36 degrees C) surgical patients. Results are expressed as a ratio of the means or relative risks and 95% confidence intervals (CI); P < 0.05 was considered statistically significant.

Results

Fourteen studies were included in analysis of blood loss, and 10 in the transfusion analysis. The median (quartiles) temperature difference between the normothermic and hypothermic patients among studies was 0.85 degrees C (0.60 degrees C versus 1.1 degrees C). The ratio of geometric means of total blood loss in the normothermic and hypothermic patients was 0.84 (0.74 versus 0.96), P = 0.009. Normothermia also reduced transfusion requirement, with an overall estimated relative risk of 0.78 (95% CI 0.63, 0.97), P = 0.027.

Conclusion

Even mild hypothermia (<1 degree C) significantly increases blood loss by approximately 16% (4-26%) and increases the relative risk for transfusion by approximately 22% (3-37%). Maintaining perioperative normothermia reduces blood loss and transfusion requirement by clinically important amounts.
Measuring the Body Composition of Preterm and Term Neonates: From Research to Clinical Applications
Authors: Roggero Paola , Giannì Maria Lorella , Amato Orsola , Agosti Massimo , Fumagalli Monica , Mosca Fabio
Published: March 2009

Assessment of body and weight gain composition is one of the major keys for the evaluation of nutritional requirements in preterm and term infants. The changes in body composition during the first years of life seem to play an important role in the nutritional programming of adult morbidity. Noninvasive and indirect techniques are the most suitable methods for measuring body composition in preterm and term infants. Most of these techniques are used in clinical practice, whereas others are used mainly for research.
Tegaserod Use in Children: A Single‐center Experience
Authors: Liem Olivia , Mousa Hayat M , Benninga Marc A , Di Lorenzo Carlo
Published: March 2009

Background:

Tegaserod is increasingly prescribed by pediatric gastroenterologists even though there are few published data concerning its use in children. The aim of this study was to describe the authors' experience with tegaserod in children.

Patients and Methods

: Patients treated with tegaserod from 2004 through 2006 were included in this study. Defecation and fecal incontinence frequency and global assessment of relief of symptoms were assessed.

Results:

Seventy‐two patients (44 girls) ranging in age from 1.1 to 18.3 years constitute the patient sample of this report. The median age was 10 years and the median follow‐up after initiation of tegaserod treatment was 11.3 months (range 2.3–45.2 months). Indications to prescribe tegaserod were constipation (58%) and a variety of other conditions including functional dyspepsia or inflammatory bowel disease (42%). Defecation frequency increased after tegaserod use (1 vs 7/week, P < 0.001) and presence of fecal incontinence decreased (47% vs 23%, P < 0.001) in the constipation group. Parents rated relief of constipation as moderate or significant in 71% of cases in the constipation group. In the group with other indications to start tegaserod therapy, moderate or significant relief of abdominal pain and bloating was noted in 64% and 68% of patients, respectively. The median dose of tegaserod prescribed was 0.22 mg · kg−1 · day−1 (range 0.05–0.87 mg · kg−1 · day−1). Adverse events were observed in 32% of the patients. The most common side effects were self‐limiting diarrhea (20%) and abdominal pain (8%). Only one patient discontinued tegaserod because of side effects; this patient experienced pain at his cecostomy site.

Conclusions:

Tegaserod seems to relieve a variety of functional gastrointestinal symptoms in children. Further randomized controlled studies are needed to support the specific pediatric target of prescribing tegaserod.
Simvastatin Restores Ischemic Preconditioning in the Presence of Hyperglycemia through a Nitric Oxide–mediated Mechanism
Authors: Gu Weidong , Kehl Franz , Krolikowski John G. , Pagel Paul S. , Warltier David C. , Kersten Judy R.
Published: March 2009

Background

A growing body of evidence indicates that statins decrease perioperative cardiovascular risk and that these drugs may be particularly efficacious in diabetes. Diabetes and hyperglycemia abolish the cardioprotective effects of ischemic preconditioning (IPC). The authors tested the hypothesis that simvastatin restores the beneficial effects of IPC during hyperglycemia through a nitric oxide-mediated mechanism.

Methods

Myocardial infarct size was measured in dogs (n = 76) subjected to coronary artery occlusion and reperfusion in the presence or absence of hyperglycemia (300 mg/dl) with or without IPC in separate groups. Additional dogs received simvastatin (20 mg orally daily for 3 days) in the presence or absence of IPC and hyperglycemia. Other dogs were pretreated with N-nitro-l-arginine methyl ester (30 mg intracoronary) with or without IPC, hyperglycemia, and simvastatin.

Results

Ischemic preconditioning significantly (P < 0.05) reduced infarct size (n = 7, 7 +/- 2%) as compared with control (n = 7, 29 +/- 3%). Hyperglycemia (n = 7), simvastatin (n = 7), N-nitro-l-arginine methyl ester alone (n = 7), and simvastatin with hyperglycemia (n = 6) did not alter infarct size. Hyperglycemia (n = 7, 24 +/- 2%), but not N-nitro-l-arginine methyl ester (n = 5, 10 +/- 1%), blocked the protective effects of IPC. Simvastatin restored the protective effects of IPC in the presence of hyperglycemia (n = 7, 14 +/- 1%), and this beneficial action was blocked by N-nitro-l-arginine methyl ester (n = 7, 29 +/- 4%).

Conclusions

The results indicate that simvastatin restored the cardioprotective effects of IPC during hyperglycemia by nitric oxide-mediated signaling. The results also suggest that enhanced cardioprotective signaling could be a mechanism for statin-induced decreases in perioperative cardiovascular risk.
Postoperative Bleeding in Cardiac Surgery
Authors: Iribarren Jose L. , Jimenez Juan J. , Hernández Domingo , Brouard Maitane , Riverol Debora , Lorente Leonardo , de La Llana Ramiro , Nassar Ibrahim , Perez Rosalia , Martinez Rafael , Mora Maria L.
Published: March 2009

Background

Plasminogen activator inhibitor 1 (PAI-1) attenuates the conversion of plasminogen to plasmin. Polymorphisms of the PAI-1 gene are associated with varying PAI-1 levels and risk of prothrombotic events in nonsurgical patients. The purpose of this study, a secondary analysis of a clinical trial, was to investigate whether PAI-1 genotype affects the efficacy of tranexamic acid (TA) in reducing postoperative chest tube blood loss of patients undergoing cardiopulmonary bypass.

Methods

Fifty patients were classified according to PAI-1 genotype (4G/4G, 4G/5G, or 5G/5G). Twenty-four received 2 g TA before and after cardiopulmonary bypass, whereas 26 received placebo. The authors recorded data related to coagulation, fibrinolysis, and bleeding before surgery, at admission to the intensive care unit (0 h), and 4 and 24 h later.

Results

In patients not receiving TA, those with the 5G/5G genotype had significantly higher chest tube blood loss and transfusion requirements compared with patients with the other genotypes at all time points. Patients with the 5G/5G genotype receiving TA showed significantly lower blood loss compared with the placebo group. There were no significant differences in blood loss or transfusion requirements between patients with the 4G/4G genotype when TA was used.

Conclusions

Plasminogen activator inhibitor-1 5G/5G homozygotes who did not receive TA showed significantly greater postoperative bleeding than patients with other PAI-1 genotypes. 5G/5G homozygotes who received TA showed the greatest blood-sparing benefit.
Age-related Attenuation of Isoflurane Preconditioning in Human Atrial Cardiomyocytes
Authors: Mio Yasushi , Bienengraeber Martin W. , Marinovic Jasna , Gutterman David D. , Rakic Mladen , Bosnjak Zeljko J. , Stadnicka Anna
Published: March 2009

Background

Clinical trials suggest that anesthetic-induced preconditioning (APC) produces cardioprotection in humans, but the mechanisms of APC and significance of aging for APC in humans are not well understood. Here, the impact of age on the role of two major effectors of APC, mitochondria and sarcolemmal adenosine triphosphate-sensitive potassium (sarcKATP) channels, in preconditioning of the human atrial myocardium were investigated.

Methods

Right atrial appendages were obtained from adult patients undergoing cardiac surgery and assigned to mid-aged (MA) and old-aged (OA) groups. APC was induced by isoflurane in isolated myocardium and isolated cardiomyocytes. Mitochondrial oxygen consumption measurements, myocyte survival testing, and patch clamp techniques were used to investigate mitochondrial respiratory function and sarcKATP channel activity.

Results

After in vitro APC with isoflurane, the respiratory function of isolated mitochondria was better preserved after hypoxia-reoxygenation stress in MA than in OA. In isolated intact myocytes, APC significantly decreased oxidative stress-induced cell death in MA but not in OA, and isoflurane protection from cell death was attenuated by the sarcKATP channel inhibitor HMR-1098. Further, the properties of single sarcKATP channels were similar in MA and OA, and isoflurane sensitivity of pinacidil-activated whole cell KATP current was no different between MA and OA myocytes.

Conclusion

Anesthetic-induced preconditioning with isoflurane decreases stress-induced cell death and preserves mitochondrial respiratory function to a greater degree in MA than in OA myocytes; however, sarcKATP channel activity is not differentially affected by isoflurane. Therefore, effectiveness of APC in humans may decrease with advancing age partly because of altered mitochondrial function of myocardial cells.
Neuromuscular Involvement in Nephrogenic Systemic Fibrosis
Authors: Keyrouz Salah , Rudnicki Stacy A
Published: March 2009

Introduction:

Nephrogenic fibrosing dermopathy causes fibrotic skin changes in the setting of renal failure. Although this condition was initially felt to be limited to the skin, recent studies have described widespread involvement, and the term nephrogenic systemic fibrosis (NSF) has been suggested.

Objective:

To describe the clinical, electrophysiologic, and pathologic findings in three NSF patients with neuromuscular involvement.

Methods:

Case report.

Results:

Three patients developed progressive hardening of the skin and underlying fascia and muscles. Strength was difficult to assess because of limited joint mobility. electromyography/nerve conduction studies suggested involvement of both nerve and muscle. Muscle biopsy demonstrated primarily myopathic changes with variable fibrosis.

Conclusion:

Neuromuscular involvement occurs in NSF and may be difficult to appreciate clinically because of joint and skin fibrosis.
Neuromuscular Features in the Camera-Marugo-Cohen Syndrome
Authors: Ohkoshi Norio , Matsuno-Yoshida Sayoko , Watanabe Masahiko , Tamaoka Akira
Published: March 2009

We describe the case of a 24-year-old Japanese man suffering from obesity, mental retardation, muscle weakness, camptodactyly, syndactyly, and a urinary tract cleft. His muscle weakness, which was slightly distally dominant in the extremities, was almost static and showed slow progression for several years. He had normal blood chromosomes (46, XY) and showed normal levels of sex hormones. A needle electromyographic examination of the upper- and lower-limb muscles revealed a reinnervation pattern with large-amplitude, long-duration motor unit potentials. A muscle biopsy also showed denervation and reinnervation patterns, with small-group atrophy and type grouping, with numerous small, angulated fibers. Our findings suggest that these neuromuscular features of the Camera-Marugo-Cohen syndrome are caused by neurogenic changes rather than myogenic changes.
A Comparison of the Effectiveness of Intravenous Immunoglobulin and Plasma Exchange as Preoperative Therapy of Myasthenia Gravis
Authors: Jensen Paul , Bril Vera
Published: March 2009

Objectives:

Immunomodulation with plasma exchange is effective in preparing patients for thymectomy. Newer forms of immunomodulation, such as intravenous immunomodulation, require evaluation in this clinical setting.

Methods:

We conducted a retrospective chart review to determine if plasma exchange and intravenous immunoglobulin had comparable effectiveness in the preoperative preparation of patients with myasthenia gravis.

Results and Conclusions:

The results show that intravenous immunoglobulin may have comparable efficacy in the preoperative preparation of patients with myasthenia gravis and that this therapy is a reasonable alternative to plasma exchange in this clinical setting.
Correction of Progressive Hearing Loss in Superior Canal Dehiscence Syndrome
Authors: Wilkinson Eric P. , Liu Gene C. , Friedman Rick A.
Published: March 2009

A 44‐year‐old woman presented with typical vestibular symptoms of superior semicircular canal dehiscence syndrome (SSCDS). In addition, the patient experienced a rapidly progressive mixed hearing loss in the affected ear prior to surgical intervention that was unresponsive to oral steroid administration. Following middle fossa craniotomy with repair of the dehiscence, the patient's mixed hearing loss resolved to normal levels with no air‐bone gap. In this report, we discuss the possible etiology of this rapidly progressive hearing loss and its implications on the differential diagnosis of patients with new onset mixed hearing losses. We also contrast the index case of progressive mixed loss with the more frequent conductive hearing loss seen in SSCDS.
Fatigue Improvement Following Endoscopic Sinus Surgery: A Systematic Review and Meta‐Analysis
Authors: Chester Alexander C. , Sindwani Raj , Smith Timothy L. , Bhattacharyya Neil
Published: March 2009

Background: Fatigue is a common symptom of chronic rhinosinusitis (CRS), yet the response of fatigue to endoscopic sinus surgery (ESS) has not been systematically evaluated.

Methods: Studies published in any language were retrieved by searching MEDLINE, EMBASE, Web of Science, Cochrane databases, and additional Web‐based sources (from 1980–2007); by examining bibliographies of retrieved articles; and by contacting investigators in the field. Studies consisting of more than 10 adult patients analyzing the response of fatigue, vitality, energy, or malaise following ESS were included. Two authors independently evaluated studies for inclusion, rated the methods, and summarized relevant data using a standardized protocol.

Results: Using within‐subject comparisons, 28 identified observational studies noted substantial improvement in fatigue after ESS. A subgroup analysis of 11 studies measuring outcomes using the 36‐Item Short Form Health Survey (SF‐36) demonstrated a moderate‐sized combined effect of 0.47 (95% confidence interval, 0.38–0.56; I2 = 0%), corresponding to a mean ± standard deviation improvement of 9.7 ± 3.4 units on the SF‐36 vitality domain scores. In studies measuring outcomes using symptom rating scores, the preoperative severity scores and improvement after surgery for fatigue were similar to the respective values for other pooled CRS symptoms.

Conclusions: All 28 studies described substantial improvement in fatigue following ESS based on presurgery and postsurgery comparisons. A subgroup analysis of 11 studies reporting results by the SF‐36 vitality domain scores demonstrated a moderate‐sized combined effect. Preoperative fatigue severity scores and improvement noted after surgery were similar to the respective values for other pooled CRS symptoms.
New Horizons in the Pathogenesis of Gastrointestinal Neuromuscular Disease
Authors: Knowles Charles H
Published: March 2009

The term “gastrointestinal neuromuscular disease” can be interpreted variably and encompasses a spectrum of paediatric and adult conditions including achalasia, pseudoobstruction, idiopathic constipation, irritable bowel syndrome, megacolon, and Hirschsprung disease. Although progress has been made in the understanding of the pathophysiology of some conditions, the aetiopathogenesis has been elucidated only in the rare minority. This review critically considers the available evidence for possible pathogenic mechanisms in these disorders.
Disorders of Interstitial Cells of Cajal
Authors: Burns Alan J
Published: March 2009

Interstitial cells of Cajal (ICCs) have, in the past 2 decades, been recognised as important elements in the regulation of gastrointestinal motility. Specifically, they have been shown to be critical for the generation and propagation of electrical slow waves that regulate the phasic contractile activity of gastrointestinal smooth muscle, and for mediating neurotransmission from enteric motor neurons to smooth muscle cells. These different functional roles are carried out by different phenotypic classes of ICC that have discrete distributions within the tunica muscularis. Identifying the functional roles of ICC within the gut has been facilitated by studying mutant mice deficient in ICC, either as a consequence of loss of the tyrosine kinase receptor, Kit, or its ligand, stem cell factor, both of which are necessary for normal ICC development. In humans, under certain pathophysiological conditions, loss or defects in ICC networks appear to play a role in the generation of certain motility disorders. Alterations in ICC distribution have been reported in conditions such as achalasia, chronic intestinal pseudoobstruction, Hirschsprung disease, inflammatory bowel diseases, and slow transit constipation. Molecular and genetic techniques are helping researchers to determine whether defects in ICC networks are the cause of motility disorders, or whether the disrupted ICC networks are a consequence of gut dysfunction.
Treatment and Outcome of Intestinal Failure Secondary to Enteric Neuromuscular Disease
Authors: Hill Susan
Published: March 2009

The clinical management of intestinal pseudoobstructive syndromes has, in the broadest of terms, 2 management strategies: optimisation of underlying gastrointestinal motor and absorptive function and, when this is inadequate, adequate nutritional support using enteral and intravenous nutrition to restore and maintain a good nutritional state and growth. With such support, a 10‐year survival rate of >80% can be achieved in the most severely affected individuals without recourse to intestinal transplantation.
Key Role of Aldosterone and Pericryptal Myofibroblast Growth in Colonic Permeability
Authors: Cristià Esther , Moretó Miquel , Naftalin Richard J
Published: March 2009

When sodium intake diminishes, both the kidney and distal colon contribute directly to sodium homeostasis. In response to a diet with low amounts of sodium, the body hormonal profile changes to produce different effects on crypt‐colon permeability and absorption and in the pericryptal sheath surrounding distal colonic crypts. This adaptation produces an increase in Na+ absorption, a decreased crypt‐wall permeability, and an activation of the growth of pericryptal myofibroblasts. The separate roles of the 2 main hormones implicated in the process, aldosterone and angiotensin II, until now have been unclear. Experiments conducted on adrenalectomized rats on low‐ and high‐sodium diets, implanted with osmotic pumps perfusing either aldosterone or angiotensin II, allow us to discriminate between the effects of these hormones. In the distal colon, aldosterone acts as a trophic agent on the myofibroblasts layer and is the key hormone controlling colonic permeability, but angiotensin II alone has no discernable direct role in the process.
Medium‐term Outcome of Endoluminal Gastroplication With the EndoCinch Device in Children
Authors: Thomson Mike , Antao Brice , Hall Sharon , Afzal Nadeem , Hurlstone Paul , Swain C Paul , Fritscher‐Ravens Annette
Published: March 2009

Objective:

Endoluminal gastroplication (EG) is emerging as a minimally invasive procedure for the treatment of gastroesophageal reflux disease (GERD). The aim of this study is to evaluate the medium‐term outcomes after EG in a pediatric patient population.

Patients and Methods:

Seventeen children with a median age of 12.4 years (range 6.1–15.9 years) with GERD underwent EG using a flexible endoscopic sewing device (EndoCinch) over a period of 3 years. Three plications were placed in the gastric tissue below the lower esophageal sphincter. Drug dose requirement, pH measurements, symptom severity and frequency, and validated Quality of Life in Reflux and Dyspepsia (QOLRAD) scores were compared before EG and 1 and 3 years after EG. Statistical analysis was performed using a Wilcoxon rank‐sum test and P < 0.05 was the threshold for significance.

Results:

All patients showed an immediate posttreatment improvement in symptom severity, symptom frequency, and quality of life scores. Completed 1‐ and 3‐year data were obtained from 16 patients. Four cases (25%) required a repeat procedure as a result of recurrence of symptoms after 2 to 24 months. Fourteen patients (88%) at 1 year and 9 patients (56%) at 3 years remained without a need for any antireflux medication. A sustained improvement in heartburn (P = 0.004), regurgitation (P = 0.017), and vomiting (P = 0.018) was seen at 3 years. The total QOLRAD score (maximum of 175) improved from a median of 87 (range 69–142) to 156 (range 111–175) at 1 year (P < 0.0001) and 153.5 (range 55–174) at 3 years (P = 0.002).

Conclusions:

EG is an effective and safe procedure in children. It is a viable option for the treatment of GERD refractory to or dependent on antireflux medications.
Enteral Erythropoietin and Iron Stimulate Erythropoiesis in Suckling Rats
Authors: Kling Pamela J , Willeitner Andrea , Dvorak Bohuslav , Blohowiak Sharon E
Published: March 2009

Objectives:

A primary objective was to evaluate whether addition of enteral iron supplementation will facilitate a systemic erythropoietic effect when feeding erythropoietin (Epo) to suckling rats. A secondary objective was to confirm that iron does not alter the previous finding that enteral Epo exerts local trophic effects on the small intestine.

Methods:

Four‐day‐old Sprague‐Dawley rats underwent gastrostomy and were fed a cow's milk–based rat milk substitute for 8 days. We studied rats fed rat milk substitute alone (control), enteral Epo 425 U · kg−1· day−1, and enteral Epo 1700 U · kg−1· day−1, and the effects of oral iron sulfate (Fe) therapy (6 mg · kg−1· day−1). Blood was collected to measure hemoglobin (Hb), reticulocytes, red cell indices, and zinc protoporphyrin/heme. To confirm previous work describing trophic effects of enteral Epo on the intestine, duodenal villous height was measured.

Results:

Hb levels in control (84 ± 1 g/L) were similar to Epo 425 (87 ± 1 g/L). Hb levels in control+Fe (97 ± 1 g/L), Epo 425+Fe (97 ± 1 g/L), and Epo 1700 (94 ± 1 g/L) were higher than control,P< 0.001, but mean Hb level in Epo 1700+Fe was higher (105 ± 1 g/L) than the other groups,P< 0.003. Mean cell volume was higher in rats receiving iron supplementation, compared with those without iron,P< 0.005. Duodenal villous height was taller in Epo 1700+Fe compared with control + Fe,P< 0.01.

Conclusions:

If combined with sufficient iron supplementation, high‐dose Epo artificially fed to suckling rats exerted a systemic erythropoietic effect in addition to the previously reported local trophic effects.
Neonatal Sublingual Vaccination with Salmonella Proteins and Adjuvant Cholera Toxin or CpG Oligodeoxynucleotides Induces Mucosal and Systemic Immunity in Mice
Authors: Huang Ching‐Feng , Wang Chih‐Chien , Wu Tzee‐Chung , Wu Keh‐Gong , Lee Chin‐Cheng , Peng Ho‐Jen
Published: March 2009

Objectives:

Salmonella enteritidis is one of the most common enteric pathogens that cause acute gastroenteritis. A vaccine that can induce systemic and mucosal immune responses by a simple, noninvasive pathway and provide protection against this mucosal pathogen is needed.

Materials and Methods:

Newborn BALB/c mice were sublingually vaccinated daily for the first 3 days with sonicated Salmonella proteins (SSP) only, or SSP combined with adjuvant CpG or cholera toxin (CT). A booster vaccination was given 7 weeks after the last treatment. Serum and saliva antibody responses, cytokine profiles of spleen cells, survival rate, and intestinal morphology after live S enteritidis challenge were investigated.

Results:

Saliva‐specific secretory IgA (SIgA) antibody responses were markedly enhanced by neonatal sublingual vaccination with SSP together with adjuvant CpG or CT. Whereas vaccination with SSP and CpG enhanced spleen cell interferon‐γ production and serum‐specific IgG2a antibody responses, vaccination with SSP and CT increased spleen cell interleukin (IL)‐4, IL‐5, IL‐6, and interferon‐γ production and serum‐specific IgG1 and IgG2a antibody responses. Vaccination with SSP and CpG or CT protected against intestinal necrosis and was associated with a higher survival rate after oral challenge with live S enteritidis. The vaccinated mice with higher specific IgG and saliva‐specific secretory IgA antibody levels had a better survival rate.

Conclusions:

Neonatal sublingual vaccination with adjuvant CpG or CT can induce both mucosal and systemic immunity and may play a crucial role in protection against enteric pathogens.
Ursodeoxycholic Acid Treatment in Preterm Infants: A Pilot Study for the Prevention of Cholestasis Associated With Total Parenteral Nutrition
Authors: Arslanoglu Sertac , Moro Guido E , Tauschel Horst‐Dietmar , Boehm Gunther
Published: March 2009

In a prospective, double‐blind, placebo‐controlled trial, the efficacy and safety of ursodeoxycholic acid (UDCA) was evaluated in preterm infants, in terms of its potential impact on fat absorption, advancement of enteral feeding, development of cholestasis, growth, nutritional status, and metabolic status. Although fecal fat excretion slightly decreased and achievement of full enteral feeding was earlier in the UDCA group, these differences were not significant. Interestingly, whereas serum γ‐glutamyl transferase activity increased during the parenteral nutrition period in the placebo group, we observed a constant and significant decrease in the UDCA group. This observation warrants further investigation to determine the utility of prophylactic UDCA in preventing cholestasis in infants with prolonged parenteral nutrition.
Gastric Emptying of Solids Is Slower in Functional Dyspepsia Unrelated to Helicobacter pylori Infection in Female Children and Teenagers
Authors: Strehl Machado Rodrigo , Reber Marialice , da Silva Patrício Francy Reis , Kawakami Elisabete
Published: March 2009

Aim:

To evaluate gastric emptying of solids in children and adolescents with functional dyspepsia with and without Helicobacter pylori infection.

Patients and Methods:

The study included 27 female patients (mean age 13.38 ± 2.81 y) with functional dyspepsia according to Rome II criteria who were selected after upper gastrointestinal endoscopy found no major mucosal abnormality. Fragments were collected from the esophagus, gastric antrum, and gastric body for histological examination and rapid urease test. H pylori infection was diagnosed according to the rapid urease test and histological appearance. The histological appearance of the gastric mucosa was evaluated according to modified Sydney criteria. A 13C‐octanoic breath test was performed after a test meal (2 slices of toasted bread, 10 g margarine, and 1 egg with 100 μLof the tracer dipped in the yolk) with 13 points of air collection in 4 hours.

Results:

Infection with H pylori was observed in 12 of 27 patients (44.4%). The gastric emptying half‐time was shorter in infected patients than in uninfected patients (mean ± SD 153.4 ± 20.0 min vs 179.2 ± 32.2 min; P = 0.019), as was the lag phase (106.3 ± 22.6 vs 126.6 ± 22.7 min; P = 0.038). There was no relationship between gastric emptying (half‐time and lag phase) and degree of histological abnormality. Vomiting and nausea were associated with slower gastric emptying in patients without H pylori gastritis more often than in infected patients.

Conclusions:

The study suggests that delayed gastric emptying can play an important role in a subgroup of dyspeptic patients, particularly those without H pylori infection who have nausea and vomiting.
Intima‐Media Thickness of Carotid Artery and Susceptibility to Atherosclerosis in Obese Children With Nonalcoholic Fatty Liver Disease
Authors: Demircioğlu Fatih , Koçyiğit Ali , Arslan Nur , Çakmakçı Handan , Hızlı Şamil , Sedat Alparslan Tuncel
Published: March 2009

Objective:

To test, via prospective case‐control study, whether measurements of carotid artery intima‐media thickness (cIMT) reflect the susceptibility to atherosclerosis in obese children with nonalcoholic fatty liver disease.

Patients and Methods:

In all, 80 obese asymptomatic normotensive adolescents (body mass index [BMI], 29.12 ± 5.13; 8.5–17.5 years) and 30 age‐ and sex‐matched nonobese healthy children (BMI 18.55 ± 2.24). Children were analysed in 4 groups: Controls formed group 1, 26 children with obesity without hepatosteatosis formed group 2, 32 children with grade 1 hepatosteatosis formed group 3, and 22 children with grade 2 or 3 hepatosteatosis formed group 4. The key parameters were BMI, liver function tests, lipid profiles, glucose, hepatic ultrasonography, and IMT of common carotid artery (CCA), left carotid bulbus (CB), and left internal carotid artery (ICA).

Results:

Comparisons of IMT measurements of left CCA, left CB, and left ICA between controls and obesity group revealed statistically significant differences (each segment P < 0.0001). There was an increase in the mean of IMT of each segment with the increase in hepatosteatosis grade (each segment P < 0.0001). The relation between the mean of IMT of left CCA, left CB, and left ICA with BMI (P = 0.001, r = 0.318), alanine aminotransferase (P = 0.007, r = 0.256), and hepatosteatosis (P < 0.0001, r = 0.470) was significant. Multiple regression analysis between left CCA, left CB, and left ICA, and age, sex, relative weight, alanine aminotransferase, total cholesterol, obesity, and hepatosteatosis grade was significant for only hepatosteatosis grade.

Conclusions:

The cIMT is significantly higher, increasing susceptibility to atherosclerosis, in obese children with hepatosteatosis than in healthy children or obese children without hepatosteatosis.
Nutritional Therapy for Glycogen Storage Diseases
Authors: Heller Solange , Worona Liliana , Consuelo Alejandra
Published: March 2009

Glycogen storage diseases (GSDs) are a group of inherited disorders characterized by enzyme defects that affect the glycogen synthesis and degradation cycle, classified according to the enzyme deficiency and the affected tissue. The understanding of GSD has increased in recent decades, and nutritional management of some GSDs has allowed better control of hypoglycemia and metabolic complications. However, growth failure and liver, renal, and other complications are frequent problems in the long‐term outcome. Hypoglycemia is the main biochemical consequence of GSD type I and some of the other GSDs. The basis of dietary therapy is nutritional manipulation to prevent hypoglycemia and improve metabolic dysfunction, with the use of continuous nocturnal intragastric feeding or cornstarch therapy at night and foods rich in starches with low concentrations of galactose and fructose during the day and to prevent hypoglycemia during the night.
Early Life Origins of Obesity: Role of Hypothalamic Programming
Authors: Bouret Sebastien G
Published: March 2009

The incidence of obesity is increasing at an alarming rate and this worldwide epidemic represents an ominous predictor of increases in diseases such as type 2 diabetes and metabolic syndrome. Epidemiological and animals studies suggest that maternal obesity and alterations in postnatal nutrition are associated with increased risks for obesity, hypertension, and type 2 diabetes in the offspring. Furthermore, there is also growing appreciation that developmental programming of neuroendocrine systems by the perinatal environment represents a possible cause for these diseases. This review article provides a synthesis of recent evidence concerning the actions of perinatal hormones and nutrition in programming the development and organization of hypothalamic circuits that regulate body weight and energy balance. Particular attention is given to the neurodevelopmental actions of insulin and leptin.
Sleep and Neurofunctions Throughout Child Development: Lasting Effects of Early Iron Deficiency
Authors: Peirano Patricio D , Algarín Cecilia R , Chamorro Rodrigo , Reyes Sussanne , Garrido Marcelo I , Duran Samuel , Lozoff Betsy
Published: March 2009

Iron‐deficiency anemia (IDA) continues to be the most common single nutrient deficiency in the world. Infants are at particular risk due to rapid growth and limited dietary sources of iron. An estimated 20% to 25% of the world's infants have IDA, with at least as many having iron deficiency without anemia. High prevalence is found primarily in developing countries, but also among poor, minority, and immigrant groups in developed ones. Infants with IDA test lower in mental and motor development assessments and show affective differences. After iron therapy, follow‐up studies point to long‐lasting differences in several domains. Neurofunctional studies showed slower neural transmission in the auditory system despite 1 year of iron therapy in IDA infants; they still had slower transmission in both the auditory and visual systems at preschool age. Different motor activity patterning in all sleep‐waking states and several differences in sleep states organization were reported. Persistent sleep and neurofunctional effects could contribute to reduced potential for optimal behavioral and cognitive outcomes in children with a history of IDA.
Omega‐3 Fatty Acids and Neural Development to 2 Years of Age: Do We Know Enough for Dietary Recommendations?
Authors: Innis Sheila M
Published: March 2009

The omega (ω)‐3 fatty acids are essential nutrients, explained by the absence of a Δ‐15 desaturase in mammalian cells. The ω‐3 fatty acids are found in the diet as α‐linolenic acid (18:3ω‐3) and eicosapentaenoic acid (20:5ω‐3), as well as docosahexaenoic acid (DHA), with different functions of each of the ω‐3 fatty acids in different cells. One essential role of the ω‐3 fatty acids is fulfilled by the 22 carbon DHA (22:6ω‐3). Depletion of DHA from brain and retina interferes with normal neurogenesis and neurological function, and visual signaling pathways. Observation and intervention studies with pregnant and lactating women, and with infants fed some formulas show that dietary DHA is associated with higher scores on tests of visual and neural development in infants and children. The estimated average requirement and variability in requirement among individuals both of which are needed to set dietary recommended intakes (DRIs) for the different ω‐3 fatty acids are unknown. However, because ω‐3 fatty acids are essential, adequate intakes to minimize risk of poor neural development and function can be justified, but dose‐response data to provide a safe upper limit with different ω‐6 fatty acid intakes are needed. Dietary recommendations do affect the food supply and supplements and are used in labeling, all impacting population health. When scientific information is incomplete, consideration must be given to the implications of recommendations that focus on individual nutrients, rather than dietary patterns such as breast‐feeding and consuming fish that promote health and minimize disease risk.
Integrating siRNA and protein–protein interaction data to identify an expanded insulin signaling network
Authors: Tu Zhidong , Argmann Carmen , Wong Kenny K. , Mitnaul Lyndon J. , Edwards Stephen , Sach Iliana C. , Zhu Jun , Schadt Eric E.
Published: March 2009

Insulin resistance is one of the dominant symptoms of type 2 diabetes (T2D). Although the molecular mechanisms leading to this resistance are largely unknown, experimental data support that the insulin signaling pathway is impaired in patients who are insulin resistant. To identify novel components/modulators of the insulin signaling pathway, we designed siRNAs targeting over 300 genes and tested the effects of knocking down these genes in an insulin-dependent, anti-lipolysis assay in 3T3-L1 adipocytes. For 126 genes, significant changes in free fatty acid release were observed. However, due to off-target effects (in addition to other limitations), high-throughput RNAi-based screens in cell-based systems generate significant amounts of noise. Therefore, to obtain a more reliable set of genes from the siRNA hits in our screen, we developed and applied a novel network-based approach that elucidates the mechanisms of action for the true positive siRNA hits. Our analysis results in the identification of a core network underlying the insulin signaling pathway that is more significantly enriched for genes previously associated with insulin resistance than the set of genes annotated in the KEGG database as belonging to the insulin signaling pathway. We experimentally validated one of the predictions, S1pr2, as a novel candidate gene for T2D.
Practitioner assessments of ‘good enough’ parenting: factorial survey
Authors: Taylor Julie , Lauder William , Moy Maxine , Corlett Jo
Published: March 2009

Aim.  The aim of this study was to measure health visitors’ professional judgements on ‘good enough’ parenting and identify what factors and combinations of these are important when making such judgements.

Background.  The relationship between parenting and child health is unclear. Whilst agreement exists that ‘good enough’ parenting requires boundary setting, consistency and putting the child’s needs first, attempting to define ‘good enough’ parenting in precise terms is complex. When faced with a complex situation, practitioners rely on relatively few factors to form judgements.

Design.  Factorial survey methods were employed using vignette techniques.

Methods.  Vignettes were constructed using previous research on those variables, which may influence nurses’ judgements, for example, accommodation and child dentition. The level of factors was randomly varied. Two thousand vignettes were administered to a sample of 200 health visitors in two Health Boards who then made a judgement about this scenario.

Analysis.  Data were analysed through multiple regression with dummy variables and one‐way analysis of variance. Regression equations for both good enough mothering and good enough parenting are reported.

Results.  The models used are significant predictors of parenting and mothering. Significant predictors on health visitor judgements’ were boundary setting in sleep behaviours, type of housing inhabited and health behaviours. Although parenting and mothering are often conflated, health visitors appear to separate these aspects when making judgements based on type of housing.

Conclusions.  Most professionals can articulate what makes a ‘good’ parent, equally they may have strong views regarding what constitutes ‘poor’ parenting. The difficulty is in determining when parenting is ‘good enough’ to provide a child with a nurturing environment.

Relevance to clinical practice.  This study suggests that practitioners move their thresholds of what is ‘good enough’ depending on a narrow range of factors. Awareness of the factors, which influence individuals’ judgements is important in safeguarding children.
Validity of the symptomatic approach used by nurses in diagnosing vaginal infections
Authors: Kisa Sezer , Taskin Lale
Published: March 2009

Aims and objectives.  To examine the validity and effectiveness of a symptomatic approach based on symptoms, administered by a nurse working in women’s health area, in identifying vaginal infections in women with or without vaginal discharge.

Design.  Survey.

Methods.  Between November 2005–August 2006, 300 married women were included. A questionnaire and vaginal discharge assessment form were used for data collection. The modified algorithm of a symptomatic approach without speculum examination was used to manage participants. Three diagnoses were made for each participant. The first diagnosis was made by the research nurse using the vaginal discharge assessment form; the second diagnosis is the clinical diagnosis which was made after the gynaecological examination by a physician; and the third diagnosis is the microscopic diagnosis made by the physician when assessing the collected specimens.

Results.  In the methodological part of this study, the sensitivity, specificity, positive predictive value and negative predictive value of the symptomatic approach were 91·5, 69·7, 87·7 and 77·5%, respectively. The symptomatic approach had 27·7% sensitivity for bacterial vaginosis, 16·6% for trichomonas vaginalis and 62·8% for candida albicans, compared to the microscopic results. The sensitivity of the approach was higher for the identification of candidiasis compared to bacterial vaginosis and trichomonas vaginalis.

Conclusion.  From the results, it is suggested that the symptomatic approach model can be used by nurses who work in women’s health area to diagnose vaginal infections.

Relevance to clinical practice.  This study showed that trained clinician nurses will be able to diagnose and manage vaginal infections – especially candidiasis – by using the symptomatic approach. Moreover, the symptomatic approach will encourage women not to delay or fail to seek treatment for their health problems, especially for vaginal infections in conservative societies.
The influence of environment and life‐history traits on the distribution of genes and individuals: a comparative study of 11 rainforest trees
Authors: ROSSETTO M. , CRAYN D. , FORD A. , MELLICK R. , SOMMERVILLE K.
Published: March 2009

This study investigates patterns of genetic connectivity among 11 co‐distributed tropical rainforest tree species from the genusElaeocarpusacross a biogeographic barrier, the Black Mountain Corridor (BMC) in the Australian Wet Tropics (AWT). We analysed a combination of allelic and flanking region sequence data from microsatellite markers, and evaluated the relative influence of environmental preferences and functional traits on genetic diversity and gene flow. The results indicate that only in three species geographic structuring of haplotype distribution reflects a north vs. south of the BMC pattern. Environmental factors linked with altitude were recognized as affecting genetic trends, but the selective processes operating on upland species appear to be associated with competitiveness and regeneration opportunities on poor soil types rather than climate variables alone. In contrast to previous observations within southeastern Australian rainforests, genetic differentiation in the AWT appears to be associated with small‐fruited rather than large‐fruited species, highlighting how external factors can influence the dispersal dimension. Overall, this study emphasizes the importance of considering functional and environmental factors when attempting generalizations on landscape‐level patterns of genetic variation. Understanding how plant functional groups respond to environmental and climatic heterogeneity can help us predict responses to future change.
Absence of Tyrosinase‐Related Protein‐2/Dopachrome Tautomerase Transcripts in PBMCs from Vitiligo Patients
Authors: Bam M. , Bagchi T.
Published: March 2009

Tolerance is achieved by mechanisms occurring in both the thymus and periphery. Several reports have shown that presence of an antigen in the peripheral circulation results in tolerance induction. These reports imply that absence of a self‐antigen can lead to induction of autoimmunity. Here, we show that tyrosinase‐related protein 2 (TRP‐2) transcript is not detected in the peripheral blood mononuclear cells (PBMC) of vitiligo patients but is detected in healthy controls. Our result indicates that probably due to lack of expression in the PBMC, TRP‐2 is not available for induction and maintenance of peripheral tolerance in vitiligo patients. It is also reported by others that co‐stimulatory molecules are required for the initiation of autoimmune diseases in experimental models. We therefore analysed the transcript levels of these costimulatory molecules in vitiligo patients and healthy controls. We observed that the transcripts of B7.2 and CD40 molecules are more or less similar in both patients and controls. We could not detect B7.1 in any of the human subjects. Thus, we conclude that the antigen presenting cells (APC) are not in an activated state and that constitutively activated APC are possibly not required for the progression of the disease once it has been initiated.