bluuebunny/crossref_metadata_2025 huggingface dataset:
Handgrip performance in relation to self-perceived fatigue, physical functioning and circulating IL-6 in elderly persons without inflammation
Authors: Bautmans Ivan , Gorus Ellen , Njemini Rose , Mets Tony
Published: March 2007

Background

Low grip strength is recognized as one of the characteristics of frailty, as are systemic inflammation and the sensation of fatigue. Contrary to maximal grip strength, the physical resistance of the muscles to fatigue is not often included in the clinical evaluation of elderly patients. The aim of this study was to investigate if the grip strength and the resistance of the handgrip muscles to fatigue are related to self-perceived fatigue, physical functioning and circulating IL-6 in independently living elderly persons.

Methods

Forty elderly subjects (15 female and 25 male, mean age 75 ± 5 years) were assessed for maximal grip strength, as well as for fatigue resistance and grip work (respectively time and work delivered until grip strength drops to 50% of its maximum during sustained contraction), self perceived fatigue (VAS-Fatigue, Mob-Tiredness scale and the energy & fatigue items of the WHOQOL-100), self rated physical functioning (domain of physical functioning on the MOS short-form) and circulating IL-6. Relationships between handgrip performance and the other outcome measures were assessed.

Results

In the male participants, fatigue resistance was negatively related to actual sensation of fatigue (VAS-F, p < .05) and positively to circulating IL-6 (p < .05). When corrected for body weight, the relations of fatigue resistance with self-perceived fatigue became stronger and also apparent in the female. Grip strength and grip work were significantly related with several items of self-perceived fatigue and with physical functioning. These relations became more visible by means of higher correlation coefficients when grip strength and grip work were corrected for body weight.

Conclusion

Well functioning elderly subjects presenting less handmuscle fatigue resistance and weaker grip strength are more fatigued, experience more tiredness during daily activities and are more bothered by fatigue sensations. Body weight seems to play an important role in the relation of muscle performance to fatigue perception. Elderly patients complaining from fatigue should be physically assessed, both evaluating maximal grip strength and fatigue resistance, allowing the calculation of grip work, which integrates both parameters. Grip work might best reflect the functional capacity resulting from the development of a certain strength level in relation to the time it can be maintained.
SOD2polymorphisms: unmasking the effect of polymorphism on splicing
Authors: Shao Jing , Chen Lishan , Marrs Brian , Lee Lin , Huang Hai , Manton Kenneth G , Martin George M , Oshima Junko
Published: March 2007

Background

The SOD2 gene encodes an antioxidant enzyme, mitochondrial superoxide dismutase. SOD2 polymorphisms are of interest because of their potential roles in the modulation of free radical-mediated macromolecular damage during aging.

Results

We identified a new splice variant of SOD2 in human lymphoblastoid cell lines (LCLs). The alternatively spliced product was originally detected by exon trapping of a minigene in order to examine the consequences of an intronic polymorphism found upstream of exon 4 (nucleotide 8136, 10T vs 9T). Examination of the transcripts derived from the endogenous loci in five LCLs with or without the intron 3 polymorphism revealed low levels of an in-frame deletion of exon 4 that were different from those detected by the exon trap assay. This suggested that exon trapping of the minigene unmasked the effect of the 10T vs 9T polymorphism on the splicing of the adjacent exon.

We also determined the frequencies of single nucleotide polymorphisms in a sample of US African-Americans and non-African-Americans ages 65 years and older who participated in the 1999 wave of the National Long Term Care Survey (NLTCS). Particularly striking differences between African-Americans and non-African-Americans were found for the frequencies of genotypes at the 10T/9T intron 3 polymorphism.

Conclusion

Exon trapping can unmask in vitro splicing differences caused by a 10T/9T intron 3 polymorphism. Given the recent evidence that SOD2 is in a region on chromosome 6 linked to susceptibility to hypertension, it will be of interest to investigate possible associations of this polymorphism with cardiovascular disorders.
Caveolin-1 sensitizes rat pituitary adenoma GH3 cells to bromocriptine induced apoptosis
Authors: Jiang Yan-Nian , Li Yi-Hung , Ke Meng-Wei , Tseng Ting-Yu , Tang Yueh-Bih , Huang Mu-Chiou , Cheng Winston Teng-Kuei , Ju Yu-Ten
Published: March 2007

Background

Prolactinoma is the most frequent pituitary tumor in humans. The dopamine D2 receptor agonist bromocriptine has been widely used clinically to treat human breast tumor and prolactinoma through inhibition of hyperprolactinemia and induction of tumor cell apoptosis, respectively, but the molecular mechanism of bromocriptine induction of pituitary tumor apoptosis remains unclear. Caveolin-1 is a membrane-anchored protein enriched on caveolae, inverted flask-shaped invaginations on plasma membranes where signal transduction molecules are concentrated. Currently, caveolin-1 is thought to be a negative regulator of cellular proliferation and an enhancer of apoptosis by blocking signal transduction between cell surface membrane receptors and intracellular signaling protein cascades. Rat pituitary adenoma GH3 cells, which express endogenous caveolin-1, exhibit increased apoptosis and shrinkage after exposure to bromocriptine. Hence, the GH3 cell line is an ideal model for studying the molecular action of bromocriptine on prolactinoma.

Results

The expression of endogenous caveolin-1 in GH3 cells was elevated after bromocriptine treatment. Transiently expressed mouse recombinant caveolin-1 induced apoptosis in GH3 cells by enhancing the activity of caspase 8. Significantly, caveolin-1 induction of GH3 cell apoptosis was sensitized by the administration of bromocriptine. Phosphorylation of caveolin-1 at tyrosine 14 was enhanced after bromocriptine treatment, suggesting that bromocriptine-induced phosphorylation of caveolin-1 may contribute to sensitization of apoptosis in GH3 cells exposed to bromocriptine.

Conclusion

Our results reveal that caveolin-1 increases sensitivity for apoptosis induction in pituitary adenoma GH3 cells and may contribute to tumor shrinkage after clinical bromocriptine treatment.
Solitary metastatic cancer to the thyroid: a report of five cases with fine-needle aspiration cytology
Authors: Lee Mark W , Batoroev Yuri K , Odashiro Alexandre N , Nguyen Gia-Khanh
Published: March 2007

Three men and 2 women with ages ranging from 37 to 70 years, clinically and histologically confirmed solitary, palpable metastatic cancers to the thyroid (SMCT) and preoperative cytologic investigation of their thyroid lesions by fine-needle aspiration (FNA), were reviewed. Four patients were known to have a solid cancer treated by radical surgery 1 to 4 years prior [1 bronchogenic squamous cell carcinoma, 1 parotid adenoid cystic carcinoma, 1 renal cell carcinoma (RCC) and 1 cutaneous melanoma], and 1 patient had no past history of cancer. Direct smears prepared from the patients’ thyroid FNAs were fixed in 95% ethanol and stained with the Papanicolaou method. In 3 cases, immunostaining of the aspirated tumor cells with thyroglobulin antibody was performed, and in 1 case an aspiration smear was stained with commercial HMB-45 antibody. A correct cytodiagnosis of metastatic cancer to the thyroid was made in all 5 cases. In 1 patient the thyroid FNA revealed a metastatic RCC that led to the discovery of a clinically occult RCC. All 5 patients died of metastatic disease 27 to 40 months after surgical resection of their SMCTs.
Knee meniscal extrusion in a largely non-osteoarthritic cohort: association with greater loss of cartilage volume
Authors: Ding Changhai , Martel-Pelletier Johanne , Pelletier Jean-Pierre , Abram François , Raynauld Jean-Pierre , Cicuttini Flavia , Jones Graeme
Published: March 2007

We conducted a longitudinal study (duration 2 years), including 294 individuals (mean age 45 years, 58% female), in order to examine associations between meniscal extrusion, knee structure, radiographic changes and risk factors for osteoarthritis (OA) in a largely non-osteoarthritic cohort. Meniscal extrusion, tibiofemoral cartilage defect score and cartilage volume, and tibial plateau bone area were determined using T1-weighted fat-saturated magnetic resonance imaging. At baseline the presence of medial meniscal extrusion was significantly associated with body mass index (odds ratio [OR] per kg/m2 = 1.13, 95% confidence interval [CI] = 1.02–1.25), past knee injury (positive versus negative history: OR = 3.73, 95% CI = 1.16–11.97), medial tibial bone area (OR per cm2 = 1.37, 95% CI = 1.02–1.85), and osteophytes (OR per grade = 4.89, 95% CI = 1.59–15.02). Two-year longitudinal data revealed that medial meniscal extrusion at baseline was associated with a greater rate of loss of medial tibiofemoral cartilage volume (extrusion versus no extrusion: -1.4%/year; P < 0.05) and greater risk for increased medial femoral cartilage defects (OR = 2.59, 95% CI = 1.14–5.86) and lateral tibial cartilage defects (OR = 2.64, 95% CI = 1.03–6.76). However, the latter two associations became nonsignificant after adjustment for tibial bone area and osteophytes. This study suggests that increasing body mass index and bone size, past knee injury, and osteophytes may be causally related to meniscal extrusion. Most importantly, meniscal extrusion at baseline is associated with greater loss of knee cartilage over 2 years, and this seems to be mediated mostly by subchondral bone changes, suggesting extrusion represents one pathway between bone expansion and cartilage loss.
Altered Expression of Genes Involved in Regulation of Vitamin A Metabolism, Solute Transportation, and Cytoskeletal Function in the Androgen-Insensitive Tfm Mouse Testis
Authors: O’Shaughnessy P. J. , Abel M. , Charlton H. M. , Hu B. , Johnston H. , Baker P. J.
Published: March 2007

Androgens are essential for the development and maintenance of spermatogenesis, but the underlying mechanisms of androgen action in the testis remain unclear. To help clarify these mechanisms, gene expression was measured in testes of pubertal (20 d old), androgen-insensitive, testicular feminized (Tfm) mice and in normal controls. Using microarrays (Affymetrix chips 430A and 430B), initial data identified a large number of genes down-regulated in the Tfm testis (>4700). These genes were largely of germ cell origin, reflecting the arrest of spermatogenesis that is apparent in the 20-d-old Tfm testis. Subsequent screening in vitro and in silico of this gene set identified 20 genes of a somatic tubular origin that were significantly down-regulated in the Tfm testis and six genes that were significantly up-regulated. Altered expression of these genes was confirmed by real-time PCR, and genes down-regulated in the Tfm testis were shown to be up-regulated in testes of hypogonadal (hpg) mice treated with androgen. In a developmental study using real-time PCR most of the regulated genes showed normal expression during fetal and neonatal development and deviated from control only between 10 and 20 d. In all cases, expression was also reduced in the adult, although interpretation is more complex because of the inherent cryptorchidism in the adult Tfm mouse. Of the total number of somatic genes showing differential expression in the Tfm testis, 50% were associated with three separate groups of genes involved in regulation of vitamin A metabolism, solute transportation, and cytoskeletal function. Thus, effects of androgens on tubular function and spermatogenesis may be mediated in part through regulation of the tubular environment and control of retinoic acid concentrations.
ERK- and JNK-signalling regulate gene networks that stimulate metamorphosis and apoptosis in tail tissues of ascidian tadpoles
Authors: Chambon Jean-Philippe , Nakayama Akie , Takamura Katsumi , McDougall Alex , Satoh Noriyuki
Published: March 2007

In ascidian tadpoles, metamorphosis is triggered by a polarized wave of apoptosis, via mechanisms that are largely unknown. We demonstrate that the MAP kinases ERK and JNK are both required for the wave of apoptosis and metamorphosis. By employing a gene-profiling-based approach, we identified the network of genes controlled by either ERK or JNK activity that stimulate the onset of apoptosis. This approach identified a gene network involved in hormonal signalling, in innate immunity, in cell-cell communication and in the extracellular matrix. Through gene silencing, we show that Ci-sushi,a cell-cell communication protein controlled by JNK activity, is required for the wave of apoptosis that precedes tail regression. These observations lead us to propose a model of metamorphosis whereby JNK activity in the CNS induces apoptosis in several adjacent tissues that compose the tail by inducing the expression of genes such as Ci-sushi.
Extended surveillance of gonorrhoea in Scotland 2003
Authors: Young Hugh , McElhinney J , Palmer H M ,   The Scottish gonococcal surveillance contributors
Published: March 2007

In 2003, a national surveillance of demographic, behavioural, clinical and laboratory data on gonorrhoea at genitourinary (GU) medicine clinics in Scotland was undertaken. The data-set represented 77% of all gonorrhoea cases. Findings were compared with data reported from England and Wales. Young women (16–19 years) and young men (20–24. years) represented the greatest proportion of heterosexual infections in Scotland (36 and 30%, respectively) and in England and Wales (37 and 32%, respectively). In Scotland (relative to England and Wales), men who have sex with men (MSM) accounted for more of the total gonorrhoea; there were more heterosexuals aged 45+ years; fewer belonged to ethnic minorities; fewer had had gonorrhoea previously; more heterosexual men had a sexual partner abroad; ciprofloxacin resistance was higher. During the year, first-line therapy changed from ciprofloxacin to a third-generation cephalosporin. Extended surveillance for gonorrhoea is vital in guiding appropriately targeted interventions as the epidemiology of gonorrhoea may differ in neighbouring countries.
Surveillance of sexually transmitted diseases in general practice: a description of trends in the Royal College of General Practitioners Weekly Returns Service between 1994 and 2001
Authors: Simms I , Fleming D M , Lowndes C M , Smith G E , Chapman R S
Published: March 2007

This paper describes the incidence of sexually transmitted infections (STIs) recorded in the Weekly Returns Service (WRS) between 1994 and 2001. There were approximately 76,500 new diagnoses of STIs (7500 males, 71,000 females) and associated syndromes. Candidiasis was the commonest condition reported in males and females followed by pelvic inflammatory disease. The ratio of males to females was 7.1 for non-specific urethritis, and 9.1 and 2.1 for Reiter's syndrome and pediculosis pubis, respectively. The incidence of anogenital warts and genital herpes changed little over time. New diagnoses of genital herpes were higher in females than in males (ratio 2.8:1), whereas the mean annual incidence of genital warts was similar in males and females. The WRS provides an insight into the burden of STI diagnoses, and diagnoses related to STIs that are managed in general practice, and as such has the potential to make a substantial contribution to STI surveillance in England.
'I'm OK?' Evaluation of a new walk-in quick-check clinic
Authors: Handy P , Pattman R S , Richards J
Published: March 2007

Following concerns about asymptomatic people having to wait 2–3 weeks for a standard appointment for screening a new 'I'm OK?' drop-in, nurse-led clinic for the worried well was devised and evaluated after the first 21 weeks (509 patients). Without overt advertising the clinic has run to near capacity and has proved popular, with 98% stating that they would attend such a clinic in the future.

The chlamydia detection rate was 9% in women and 4% in men, with one case of asymptomatic rectal gonorrhoea and two of HIV infection diagnosed allowing early treatment intervention. HIV testing was accepted by 94% of attendees and initial hepatitis B vaccination by 93% of homosexual/bisexual men.

This approach deflects such routine cases, potentially allowing increased time at standard clinic sessions for those with clinical problems staffed by more experienced nurses and doctors. Its success has encouraged us to develop this concept as a cost-effective way of addressing 48-hour genitourinary medicine access.
HPLC for Simultaneous Quantification of Total Ceramide, Glucosylceramide, and Ceramide Trihexoside Concentrations in Plasma
Authors: Groener Johanna EM , Poorthuis Ben JHM , Kuiper Sijmen , Helmond Mariette TJ , Hollak Carla EM , Aerts Johannes MFG
Published: March 2007

Background: Simple, reproducible assays are needed for the quantification of sphingolipids, ceramide (Cer), and sphingoid bases. We developed an HPLC method for simultaneous quantification of total plasma concentrations of Cer, glucosylceramide (GlcCer), and ceramide trihexoside (CTH).

Methods: After addition of sphinganine as internal calibrator, we extracted lipids from 50 μL plasma. We deacylated Cer and glycosphingolipids by use of microwave-assisted hydrolysis in methanolic NaOH, followed by derivatization of the liberated amino-group with o-phthaldialdehyde. We separated the derivatized sphingoid bases and lysoglycosphingolipids by HPLC on a C18 reversed-phase column with a methanol/water mobile phase (88:12, vol/vol) and quantified them by use of a fluorescence detector at λex 340 nm and λem 435 nm.

Results: Optimal conditions in the Solids/Moisture System SAM-155 microwave oven (CEM Corp.) for the complete deacylation of Cer and neutral glycosphingolipids without decomposition were 60 min at 85% power, fan setting 7. Intra- and interassay CVs were <4% and <14%, respectively, and recovery rates were 87%–113%. The limit of quantification was 2 pmol (0.1 pmol on column), and the method was linear over the interval of 2–200 μL plasma. In samples from 40 healthy individuals, mean (SD) concentrations were 9.0 (2.3) μmol/L for Cer, 6.3 (1.9) μmol/L for GlcCer, and 1.7 (0.5) μmol/L for CTH. Plasma concentrations of GlcCer were higher in Gaucher disease patient samples and of CTH in Fabry disease patient samples.

Conclusions: HPLC enables quantification of total Cer, GlcCer, and CTH in plasma and is useful for the follow-up of patients on therapy for Gaucher or Fabry disease.
Negative-Ion Chemical Ionization Gas Chromatography–Mass Spectrometry Assay for Enantioselective Measurement of Amphetamines in Oral Fluid: Application to a Controlled Study with MDMA and Driving Under the Influence Cases
Authors: Peters Frank T , Samyn Nele , Kraemer Thomas , Riedel Wim J , Maurer Hans H
Published: March 2007

Background: Enantioselective analysis of amphetamine (AM), methamphetamine (MA), 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA), and 3,4-methylenedioxyethylamphetamine (MDEA) helps interpret toxicological results. Methods have been described for various matrices, but so far not for oral fluid, a matrix of increasing importance in testing for drugs of abuse, especially in the context of driving under the influence of drugs (DUID).

Methods: After dilution with 200 μL carbonate buffer (pH 9), oral fluid samples (10–50 μL) were derivatized with S-heptafluorobutyrylprolyl chloride. The resulting diastereomers were extracted into 100 μL of cyclohexane, separated by gas chromatography (HP-5MS column), and detected by mass spectrometry in the negative-ion chemical ionization mode (GC-NICI-MS). The method was validated and applied to samples from a controlled study with MDMA and from authentic DUID cases.

Results: The derivatized AM, MA, MDA, MDMA, and MDEA enantiomers were well separated from each other. The method was linear from 5–250 μg/L per enantiomer of MDA and from 25–1250 μg/L per enantiomer of AM, MA, MDMA, and MDEA. With the exception of MDEA, analytical recoveries, repeatability, and intermediate precision were within required limits. The analyte concentrations and enantiomer ratios in the application samples correlated only weakly with corresponding published plasma data.

Conclusions: This sensitive, reliable, and fast GC-NICI-MS assay enantioselectively measures AM, MA, MDA, and MDMA in oral fluid samples. Prediction of plasma concentrations and enantiomer ratios from respective oral fluid data is not possible.
Vom (Un-)Sinn der Schreibvarianten
Authors: Jacobs Joachim
Published: March 2007

The paper analyses systematic variations in the way words are separated by spaces (WS variations) in German. In particular, WS variations in the traditional German orthography are compared with WS variations after the spelling reform of 1996. Based on a general distinction between four different kinds of spelling variants and an analysis of the WS system before and after the reform in the framework of Optimality Theory, it is shown how and why the spelling reform lead to a drastic reduction of the possibilities to express semantic differences by WS variations. Furthermore it is argued that two recent revisions of the spelling reform, although they reintroduced many WS variants that were originally banned by the spelling reform, did not succeed in restoring these possibilities.
Infant Care Patterns at Epidemiologic Study of Cystic Fibrosis Sites That Achieve Superior Childhood Lung Function
Authors: Padman Raj , McColley Susanna A. , Miller Dave P. , Konstan Michael W. , Morgan Wayne J. , Schechter Michael S. , Ren Clement L. , Wagener Jeffrey S. ,   for the Investigators and Coordinators of the Epidemiologic Study of Cystic Fibrosis
Published: March 2007

OBJECTIVE. Previous analyses of the Epidemiologic Study of Cystic Fibrosis database revealed that sites with the highest average patient lung function monitor patients and treat with antibiotics more aggressively than those where average lung function is lowest. The aim of this study was to assess whether patterns of care for infants at cystic fibrosis sites with superior average lung function in 6- to 12-year-old children showed any differences from those at the lowest outcome sites.

METHODS. We divided cystic fibrosis sites with ≥20 patients who were 6 to 12 years of age into quartiles on the basis of median forced expiratory volume in 1 second of that age group in 2003 and compared demographic and clinical characteristics and treatment patterns during the first year of enrollment for patients who were aged 0 to 3 years at those sites in 1994 to 1999. The analysis included 755 infants from 12 upper quartile sites and 743 infants from 12 lower quartile sites.

RESULTS. Upper quartile sites had more infants whose disease was diagnosed by family history or newborn screening, fewer infants with symptoms at diagnosis, higher weight for age at enrollment, more white patients, and more ΔF508 homozygotes. Medical conditions and respiratory tract microbiology differed between sites. Infants at upper quartile sites had more office and sick visits; more respiratory tract cultures; and more frequent use of intravenous antibiotics, oral corticosteroids, mast cell stabilizers, and mucolytics; but they received less chest physiotherapy, inhaled bronchodilators, oral nutritional supplements, and pancreatic enzymes.

CONCLUSIONS. Both enrollment characteristics and infant care patterns are associated with lung function outcomes in later childhood. Our analysis suggests that pulmonary function of older children may be improved through specific interventions during the first 3 years of life.
Internet-Based Home Monitoring and Education of Children With Asthma Is Comparable to Ideal Office-Based Care: Results of a 1-Year Asthma In-Home Monitoring Trial
Authors: Chan Debora S. , Callahan Charles W. , Hatch-Pigott Virginia B. , Lawless Annette , Proffitt H. Lorraine , Manning Nola E. , Schweikert Mary , Malone Francis J.
Published: March 2007

OBJECTIVE. The goal was to determine whether home asthma telemonitoring with store-and-forward technology improved outcomes, compared with in-person, office-based visits.

METHODS. A total of 120 patients, 6 to 17 years of age, with persistent asthma were assigned randomly to the office-based or virtual group. The 2 groups followed the same ambulatory clinical pathway for 12 months. Office-based group patients received traditional in-person education and case management. Virtual group patients received computers, Internet connections, and in-home, Internet-based case management and received education through the study Web site. Disease control outcome measures included quality of life, utilization of services, and symptom control.

RESULTS. A total of 120 volunteers (45 female) were enrolled. The groups were clinically comparable (office-based: 22 female/38 male; mean age: 9.0 ± 3.0 years; virtual: 23 female/37 male; mean age: 10.2 ± 3.1 years). Virtual patients had higher metered-dose inhaler with valved holding chamber technique scores than did the office-based group at 52 weeks (94% vs 89%), had greater adherence to daily asthma symptom diary submission (35.4% vs 20.8%), had less participant time (636 vs 713 patient-months), and were older. Caregivers in both groups perceived an increase in quality of life and an increase in asthma knowledge scores from baseline. There were no other differences in therapeutic or disease control outcome measures.

CONCLUSIONS. Virtual group patients achieved excellent asthma therapeutic and disease control outcomes. Compared with those who received standardized office-based care, they were more adherent to diary submission and had better inhaler scores at 52 weeks. Store-and-forward telemedicine technology and case management provide additional tools to assist in the management of children with persistent asthma.
Recurrent Expressive Aphasia as a Presentation of Cat-Scratch Encephalopathy
Authors: Fox James W. , Studley Joanna K. , Cohen Daniel M.
Published: March 2007

Cat-scratch disease is a common disease, occurring in an estimated 24000 patients annually in the United States, and is one of the most common causes of chronic lymphadenitis in children. A wide array of neurologic complications occurs as a result of cat-scratch disease. However, there have been no reports of acute-onset, self-resolving, recurrent, expressive aphasia, as we report here in an adolescent boy. In our case, establishing the diagnosis of cat-scratch encephalopathy saved time and resources and afforded the family a benign diagnosis. Cat-scratch encephalopathy must be considered in the differential diagnoses when pediatric patients present with unusual neurologic symptoms.
Screening for Depression in an Urban Pediatric Primary Care Clinic
Authors: Dubowitz Howard , Feigelman Susan , Lane Wendy , Prescott Leslie , Blackman Kenneth , Grube Lawrie , Meyer Walter , Tracy J. Kathleen
Published: March 2007

OBJECTIVES. The goals were to estimate the prevalence of parental depressive symptoms among parents at a pediatric primary care clinic and to evaluate the stability, sensitivity, specificity, and positive and negative predictive values of a very brief screen for parental depression.

METHODS. A total of 216 mothers (because 96% of caregivers were mothers, we use this term) bringing in children <6 years of age for child health supervision completed a parent screening questionnaire in a primary care clinic. The parent screening questionnaire, a brief screen for psychosocial problems developed for the study, includes 2 questions on depressive symptoms. Mothers then completed the computerized study protocol within 2 months. This included the parent screening questionnaire as well as the Beck Depression Inventory II. Different combinations of the depression questions were evaluated against Beck Depression Inventory II clinical cutoff values.

RESULTS. Twelve percent of the mothers met the Beck Depression Inventory II clinical cutoff value for at least moderate depressive symptoms. There was moderate stability of the screening questions. When a positive response to either or both of the 2 questions was considered, the sensitivity was 74%, the specificity was 80%, the positive predictive value was 36%, and the negative predictive value was 95%.

CONCLUSIONS. Maternal depressive symptoms are prevalent. A very brief screen can identify reasonably those who could benefit from additional evaluation and possible treatment. This should benefit mothers, families, and children.
Bisphosphonates: Mode of Action and Pharmacology
Authors: Russell R. Graham G.
Published: March 2007

The profound effects of the bisphosphonates on calcium metabolism were discovered over 30 years ago, and they are now well established as the major drugs used for the treatment of bone diseases associated with excessive resorption. Their principal uses are for Paget disease of bone, myeloma, bone metastases, and osteoporosis in adults, but there has been increasing and successful application in pediatric bone diseases, notably osteogenesis imperfecta. Bisphosphonates are structural analogues of inorganic pyrophosphate but are resistant to enzymatic and chemical breakdown. Bisphosphonates inhibit bone resorption by selective adsorption to mineral surfaces and subsequent internalization by bone-resorbing osteoclasts where they interfere with various biochemical processes. The simpler, non–nitrogen-containing bisphosphonates (eg, clodronate and etidronate) can be metabolically incorporated into nonhydrolysable analogues of adenosine triphosphate (ATP) that may inhibit ATP-dependent intracellular enzymes. In contrast, the more potent, nitrogen-containing bisphosphonates (eg, pamidronate, alendronate, risedronate, ibandronate, and zoledronate) inhibit a key enzyme, farnesyl pyrophosphate synthase, in the mevalonate pathway, thereby preventing the biosynthesis of isoprenoid compounds that are essential for the posttranslational modification of small guanosine triphosphate (GTP)-binding proteins (which are also GTPases) such as Rab, Rho, and Rac. The inhibition of protein prenylation and the disruption of the function of these key regulatory proteins explains the loss of osteoclast activity. The recently elucidated crystal structure of farnesyl diphosphate reveals how bisphosphonates bind to and inhibit at the active site via their critical nitrogen atoms. Although bisphosphonates are now established as an important class of drugs for the treatment of many bone diseases, there is new knowledge about how they work and the subtle but potentially important differences that exist between individual bisphosphonates. Understanding these may help to explain differences in potency, onset and duration of action, and clinical effectiveness.
Auditory Neural Maturation After Exposure to Multiple Courses of Antenatal Betamethasone in Premature Infants as Evaluated by Auditory Brainstem Response
Authors: Amin Sanjiv B. , Guillet Ronnie
Published: March 2007

OBJECTIVE. Our goal was to determine if multiple courses of antenatal betamethasone affect auditory neural maturation in 28 to 32 weeks' gestational age infants.

PATIENTS AND METHODS. A retrospective cohort study was performed to compare auditory neural maturation between premature infants exposed to 1 course of betamethasone and infants exposed to ≥2 courses of betamethasone. Inclusion criteria included all 28 to 32 weeks' gestational age infants delivered between July 1996 and December 1998 who had auditory brainstem response testing performed (80-dB click stimuli at a repetition rate of 39.9/second) within 24 hours of postnatal life as part of bilirubin-auditory studies. Infants with toxoplasmosis, rubella, cytomegalovirus, herpes infections, chromosomal disorders, unstable conditions, exposure to antenatal dexamethasone, and exposure to <1 complete course of betamethasone were excluded. Auditory waveforms were categorized into response types on response replicability and peak identification as types 1 through 4 (type 1 indicating most mature). Absolute and interpeak wave latencies were measured when applicable. Categorical and continuous variables were analyzed by using the χ2 test and Student's t test, respectively.

RESULTS. Of 174 infants studied, 123 received antenatal steroids. Of these, 50 received 1 course and 29 received ≥2 courses of betamethasone. There were no significant differences in perinatal demographics between the 2 groups. After controlling for confounding variables, there was no significant difference in mean absolute wave latencies, mean interpeak latencies, or distribution of response type between the 2 groups. There also was no significant difference in any auditory brainstem response parameters between infants exposed to 1 course of betamethasone (n = 50) and infants exposed to >2 courses of betamethasone (n = 17).

CONCLUSION. Compared with a single recommended course of antenatal steroids, multiple courses of antenatal betamethasone are not associated with a deleterious effect on auditory neural maturation in 28 to 32 weeks' gestational age infants.
Neurodevelopmental Consequences of Early Traumatic Brain Injury in 3-Year-Old Children
Authors: Keenan Heather T. , Hooper Stephen R. , Wetherington Crista E. , Nocera Maryalice , Runyan Desmond K.
Published: March 2007

OBJECTIVES. The purpose of this work was to determine cognitive and adaptive behavioral outcomes of children with traumatic brain injury acquired before age 2 years and to compare outcomes between inflicted versus noninflicted brain injury.

PATIENTS AND METHODS. All North Carolina children hospitalized in an ICU for a traumatic brain injury before age 2 years between the years 2000 and 2001 were eligible for study entry. A total of 112 surviving children were prospectively identified, 52 (46%) of whom had complete follow-up. Thirty-one control children were recruited from preschool settings. Control subjects were chosen to be demographically similar to case subjects. Child measures of cognition and adaptive behavior at age 3 years were measured and compared between children with and without traumatic brain injury and children with inflicted and noninflicted traumatic brain injury.

RESULTS. Sixty percent of injured children were >1 SD below normal on cognitive testing. Forty percent of injured children scored >1 SD below normal on adaptive behavior testing. Children with inflicted traumatic brain injury performed more poorly on tests of cognition and adaptive behavior. Glasgow Coma Scale ≥13, absence of seizures, income above twice the poverty guidelines, and high social capital were associated with improved outcomes. Injured children had lower scores than uninjured control children after adjustment for socioeconomic status.

CONCLUSIONS. Very young children with mild-to-severe traumatic brain injury as measured by the Glasgow Coma Scale are at risk for global cognitive deficits more than a year after the time of injury. Inflicted brain injury is associated with more severe injury and worse outcomes. This is less optimistic than findings in this same cohort 1 year after injury. Family characteristics seem to play a role in recovery after injury.
Comparison of Current Health, Functional Limitations, and Health Care Use of Young Adults Who Were Born With Extremely Low Birth Weight and Normal Birth Weight
Authors: Saigal Saroj , Stoskopf Barbara , Boyle Michael , Paneth Nigel , Pinelli Janet , Streiner David , Goddeeris John
Published: March 2007

OBJECTIVE. The objective of this study was to compare the current health status, physical ability, functional limitations, and health care use of extremely low birth weight and normal birth weight young adults.

METHODS. A longitudinal study was conducted of a population-based cohort of 166 extremely low birth weight survivors (501–1000 g birth weight; 1977–1982 births) and a group of 145 sociodemographically comparable normal birth weight individuals. Current health status, history of illnesses, hospitalizations, use of health resources, and physical self-efficacy were assessed through questionnaires that were administered to the young adults by masked interviewers.

RESULTS. Individuals completed the assessments at a mean age of 23 years. Neurosensory impairments were identified in 27% of extremely low birth weight and 2% of normal birth weight individuals. No differences were reported in the current health status for physical or mental summary scores. Extremely low birth weight young adults reported a higher prevalence of chronic health conditions in the past 6 months. A significantly higher proportion of extremely low birth weight individuals had functional limitations in seeing, hearing, and dexterity and experienced clumsiness and learning difficulties. Except for prescription glasses, medications for depression, and home-care services for extremely low birth weight individuals, there were no significant differences between groups in use of health care resources. Extremely low birth weight individuals had significantly weaker hand grip strength and lower scores for physical self-efficacy, perceived physical ability, and physical self-confidence.

CONCLUSIONS. Extremely low birth weight young adults seem to enjoy similar current health status to their normal birth weight peers. However, they continue to have significantly poorer physical abilities and a higher prevalence of chronic health conditions and functional limitations. Contrary to expectations, they do not pose a significant burden to the health care system at young adulthood.
Identification of High Proliferative Potential Precursors with Hemangioblastic Activity in the Mouse Aorta-Gonad- Mesonephros Region
Authors: Yao Huiyu , Liu Bing , Wang Xiaoyan , Lan Yu , Hou Ning , Yang Xiao , Mao Ning
Published: March 2007

Hemangioblast, a precursor possessing hematopoietic and endothelial potential, is identified as the blast colony-forming cell in the murine gastrulating embryos (E7.0–E7.5). Whether hemangioblast exists in the somite-stage embryos is unknown, even though hemogenic endothelium is regarded as the precursor of definitive hematopoiesis in the aorta-gonad-mesonephros (AGM) region. To address the issue, we developed a unique three-step assay of high proliferative potential (HPP) precursors. The AGM region contained a kind of HPP precursor that displayed hematopoietic self-renewal capacity and was able to differentiate into functional endothelial cells in vitro (i.e., incorporating DiI-acetylated low-density lipoprotein, expressing von Willebrand factors, and forming network structures in Matrigel). The clonal nature was verified by cell mixing assay. However, the bilineage precursor with high proliferative potential—the HPP-hemangioblast (HA)—was not readily detected in the yolk sac (E8.25–E12.5), embryonic circulation (E10.5), placenta (E10.5–E11.5), fetal liver (E11.5–E12.5), and even umbilical artery (E11.5), reflective of its strictly spatial-regulated ontogeny. Expression of CD45, a panhematopoietic marker, distinguished hematopoietic-restricted HPP–colony-forming cell from the bipotential HPP-HA. Finally, we revealed that basic fibroblast growth factor, other than vascular endothelial growth factor or transforming growth factor-β1, was a positive modulator of the HPP-HA proliferation. Taken together, the HPP-HA represents a novel model for definitive hemangioblast in the mouse AGM region and will shed light on molecular mechanisms underlying the hemangioblast development.

Disclosure of potential conflicts of interest is found at the end of this article.
Glucose regulates AMP-activated protein kinase activity and gene expression in clonal, hypothalamic neurons expressing proopiomelanocortin: additive effects of leptin or insulin
Authors: Cai Fang , Gyulkhandanyan Armen V , Wheeler Michael B , Belsham Denise D
Published: March 2007

The mammalian hypothalamus comprises an array of phenotypically distinct cell types that interpret peripheral signals of energy status and, in turn, elicits an appropriate response to maintain energy homeostasis. We used a clonal representative hypothalamic cell model expressing proopiomelanocortin (POMC; N-43/5) to study changes in AMP-activated protein kinase (AMPK) activity and glucose responsiveness. We have demonstrated the presence of cellular machinery responsible for glucose sensing in the cell line, including glucokinase, glucose transporters, and appropriate ion channels. ATP-sensitive potassium channels were functional and responded to glucose. The N-43/5 POMC neurons may therefore be an appropriate cell model to study glucose-sensing mechanisms in the hypothalamus. In N-43/5 POMC neurons, increasing glucose concentrations decreased phospho-AMPK activity. As a relevant downstream effect, we found that POMC transcription increased with 2.8 and 16.7 mM glucose. Upon addition of leptin, with either no glucose or with 5 mM glucose, we found that leptin decreased AMPK activity in N-43/5 POMC neurons, but had no significant effect at 25 mM glucose, whereas insulin decreased AMPK activity at only 5 mM glucose. These results demonstrate that individual hypothalamic neuronal cell types, such as the POMC neuron, can have distinct responses to peripheral signals that relay energy status to the brain, and will therefore be activated uniquely to control neuroendocrine function.
Growth hormone stimulates osteoprotegerin expression and secretion in human osteoblast-like cells
Authors: Mrak E , Villa I , Lanzi R , Losa M , Guidobono F , Rubinacci A
Published: March 2007

It is presently thought that osteoprotegerin (OPG) is a cytokine involved in the regulation of osteoblast/osteoclast crosstalk and maintenance of bone mass. Recent studies showed that GH replacement therapy in GH-deficient patients was able to induce a significant increase of OPG in the plasma, as well as in the cortical and the trabecular bone. In order to determine whether GH could directly modulate OPG secretion, the effect of GH on human osteoblast-like cells (hOB) in primary culture was studied. After detecting the presence of the mRNA for the GH receptor (GHR) by RT-PCR, hOB were exposed to increasing concentrations of GH, from 0.1 to 25 ng/ml, for 24 h. The results showed that GH exposure was able to stimulate OPG secretion in a concentration-dependent manner. In addition, the OPG mRNA levels were increased, indicating that the hormone has a stimulatory effect on gene expression. The stimulatory effect on OPG expression and production was prevented by exposing the cells to tyrphostin AG490 (10 μM), an inhibitor of Janus kinase 2, which is one of the kinases involved in the intracellular pathway activated by the binding of GH to its receptor. Similar results were obtained when the cells were exposed to a receptor antagonist of GH, pegvisomant at 50 nM. GH exposure neither induced an increase in IGF-I expression nor secretion in hOB. These results suggest that the stimulation of OPG production induced by GH in hOB is specific and receptor mediated and further support the view that GH is able to modulate bone remodeling by directly influencing osteoblast–osteoclast crosstalk.
Salivary Enzyme Levels After Scaling and Interleukin‐1 Genotypes in Japanese Patients With Chronic Periodontitis
Authors: Yoshie Hiromasa , Tai Hideaki , Kobayashi Tetsuo , Oda‐Gou Emire , Nomura Yoshiaki , Numabe Yukihiro , Ito Kohichi , Kurihara Hidemi , Kamoi Kyuichi
Published: March 2007

Background: Saliva has been used as a diagnostic fluid in medicine and dentistry. It is easy to collect using non‐invasive methods. The intracellular enzymes present in saliva have been studied as markers of periodontal disease. The purpose of this study was to determine the salivary enzyme levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) after scaling and to clarify the influence of interleukin (IL)‐1 genotypes on these enzyme levels.

Methods: Forty‐nine Japanese patients with chronic periodontitis (24 men and 25 women; mean age: 55.1 years) were enrolled in this study. Measurements of clinical parameters including probing depth (PD), clinical attachment level (CAL), and bleeding on probing (BOP) and collections of stimulated whole mixed saliva were performed at baseline and 4 weeks after scaling. After evaluation of salivary AST, ALT, and LDH levels, DNA was extracted from various cells in whole saliva. IL‐1A+4845 G/T genotype was determined by polymerase chain reaction amplification, followed by enzyme digestion and electrophoresis. Statistical analysis was performed by the Wilcoxon signed‐rank and Mann‐Whitney U tests. A significant difference was set at P <0.05.

Results: Mean PD, CAL, and BOP values significantly decreased after scaling (mean ± SE: 3.2 ± 0.1 mm to 2.6 ± 0.1 mm in PD; 3.9 ± 0.2 mm to 3.3 ± 0.2 mm in CAL; and 41% ± 4% to 18% ± 3% in BOP) (P <0.001). The values of AST, ALT, and LDH were 77.0 ± 7.5, 43.9 ± 5.5, and 753.4 ± 96.5 (units per liter [U/l]) at baseline, and significantly decreased to 55.5 ± 6.5, 30.0 ± 5.5, and 394.7 ± 34.0 (U/l) after scaling, respectively (P = 0.01, P = 0.006, and P <0.001). The carriage rate of the IL‐1A+4845 allele 2 was 24.5%. No difference was noted in the decrease in PD, CAL, and BOP after scaling between the carriers (N = 12) and non‐carriers (N = 37) of IL‐1A+4845 allele 2. However, the IL‐1A allele 2 non‐carriers displayed a significant decrease in salivary AST and ALT levels (P <0.001), in contrast to the carriers who did not show any changes in the salivary levels of the enzymes after scaling.

Conclusions: These results documented that salivary AST, ALT, and LDH levels reflect inflammation and destruction of periodontal tissue, suggesting clinically useful markers following periodontal therapy. In addition, although IL‐1A+4845 alleles may not influence clinical parameters, they may influence post‐scaling values of salivary AST and ALT.
Anti‐Cardiolipin and Increased Serum Adhesion Molecule Levels in Patients With Aggressive Periodontitis
Authors: Schenkein Harvey A. , Best Al M. , Brooks Carol N. , Burmeister John A. , Arrowood James A. , Kontos Michael C. , Tew John G.
Published: March 2007

Background: We observed that a significant proportion of patients with periodontitis have elevated serum levels of β2‐glycoprotein‐I–dependent anti‐cardiolipin (anti‐CL). These prothrombotic autoantibodies, commonly found to be elevated in patients with systemic lupus erythematosus and the antiphospholipid syndrome, are associated with adverse pregnancy outcomes, such as fetal involution, prematurity, and low birth weight, and with cardiovascular sequelae, such as atherosclerosis, stroke, and myocardial infarction. Anti‐CL is known to promote vascular inflammation and thrombosis.

Methods: We measured serum levels of markers of vascular inflammation, including soluble intercellular adhesion molecule (sICAM)‐1, soluble vascular cell adhesion molecule (sVCAM)‐1, and sE‐selectin, in 190 subjects with generalized aggressive or chronic periodontitis and in 90 periodontally healthy subjects.

Results: sVCAM‐1 and sE‐selectin levels were significantly higher in patients with elevated anti‐CL (>1‐ U/ml). This relationship also was observed in the never‐smoker subset of subjects, even after correction for demographic and periodontal variables. Within the diagnostic categories, sICAM‐1, sVCAM‐1, and sE‐selectin were significantly higher in generalized aggressive periodontitis patients who had elevated anti‐CL compared to those with normal anti‐CL. Statistical correction for demographic and periodontal variables indicated that elevated anti‐CL remained significantly associated with increased sVCAM‐1 and sE‐selectin in generalized aggressive periodontitis patients.

Conclusions: Systemic markers of vascular inflammation in patients with aggressive periodontitis are associated with elevated levels of anti‐CL. We hypothesize that a subset of periodontitis patients with elevated antiphospholipid antibodies could represent a subgroup at increased risk for obstetrical and cardiovascular sequelae.