bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of tibiofemoral loading on proximal tibiofibular joint motion*
Authors: Scott Jacob , Lee Ho , Barsoum Wael , Van Den Bogert Antonie J.
Published: September 2007

The human proximal tibiofibular joint (PTFJ) and its relationship to overall knee joint mechanics have been largely unexplored. This study describes force/displacement data from experiments done on four human cadaveric knee specimens and general conclusions obtained with the help of a statistical modeling technique. Specimens were rigidly affixed at the tibia to a force plate and the femur was attached to a custom made device allowing for manual load application. Motion of the fibular head was tracked relative to the tibial plateau by means of reflective markers and a high speed digital camera synchronized with the force plate data stream. Each specimen was subjected to a range of loading conditions and a quadratic regression model was created and then used to predict the specimen's response to standardized loading conditions and compare these across specimens. Statistical analysis was performed with a three‐factor analysis of variance with repeated measures.

Proximal tibiofibular joint motion was largest in the anterior‐posterior direction with translations of 1–3 mm observed during a range of physiological loading conditions. The applied internal‐external rotation moment had a significant effect on proximal tibiofibular joint translation (P < 0.05). Effects of varus‐valgus loading and flexion angle were seen in some specimens. This study demonstrates that substantial proximal tibiofibular joint motion can occur in physiologic loading states. Preservation of proximal tibiofibular joint function, and anatomical variations which affect this function, may need to be considered when designing surgical procedures for the knee joint.
Induced abortion and risk of small‐for‐gestational‐age birth
Authors: Parazzini F , Cipriani S , Chiaffarino F , Sandretti F , Bortolus R , Chiantera V
Published: September 2007

Objective  To investigate the possibility of an association between previous induced abortion and subsequent birth of a small‐for‐gestational‐age (SGA) infant.

Design  Case–control study.

Setting  General and university hospitals.

Methods  Cases were 555 women who delivered SGA babies. Controls were 1966 women who gave birth at term (>37 weeks of gestation) to healthy infants of normal weight on randomly selected days at the hospital where cases had been identified. All women in the case and control categories were interviewed on the obstetric wards by one of a team of six interviewers. During the interviews, information was obtained regarding general socio‐demographic factors, personal characteristics and habits, gynaecological and obstetric history, general anamnesis, family history of obstetric and gynaecological diseases, and the age of the father of the child. Further information on current pregnancy and delivery was also collected. We used conditional multiple logistic regression (with age as the matching variable), with maximum likelihood fitting, to obtain odds ratios and their corresponding 95% CIs. Included in the regression equations were terms for education, plus terms significantly associated in this data set with the risk of SGA birth (smoking in pregnancy, history of SGA, gestational hypertension and parity).

Population  Women admitted to a general and a university hospital.

Results  No significant increase in the risk of SGA birth was observed in women with a previous induced abortion [odds ratio (OR) 1.0; 95% CI 0.6–1.7]. The OR for SGA birth was 1.2 (95% CI 0.7–2.1) for preterm and 1.0 (95% CI 0.7–1.4) for term SGA births.

Conclusion  This study found no association between risk of SGA birth and induced abortion.
The effect of cigarette or sheesha smoking on first‐trimester markers of Down syndrome
Authors: Ardawi MSM , Nasrat HA , Rouzi AA , Qari MH , Al‐Qahtani MH , Abuzenadah AM
Published: September 2007

Objective  To investigate the influence of cigarette or sheesha smoking on first‐trimester markers of Down syndrome.

Design  A prospective observational study.

Setting  Primary care centres and antenatal clinics of Maternity and Children Hospital, King Abdulaziz University Hospital and New Jeddah Clinic Hospital, Jeddah, Saudi Arabia.

Population  Women with a singleton pregnancy who were either nonsmokers (n= 1736) or cigarette smokers (n= 420) or sheesha smokers (n= 181).

Methods  Fetal nuchal translucency thickness (fetal NT), maternal serum free beta‐human chorionic gonadotrophin (free β‐hCG) and pregnancy‐associated plasma protein‐A (PAPP‐A) were measured at 11 weeks 0 days to 13 weeks 6 days of gestation in all women. Women were grouped according to smoking status, confirmed by maternal serum cotinine measurements, and analyte levels between groups were compared.

Main outcome measures  Fetal NT, maternal serum free β‐hCG, PAPP‐A and cotinine measurements.

Results  Compared with nonsmoking women, fetal NT was significantly increased and free β‐hCG and PAPP‐A levels were significantly decreased in both cigarette and sheesha smokers. There were significant relationships between all three markers and the number of sheeshas consumed per day.

Conclusions  Cigarette and sheesha smoking significantly affect first‐trimester markers of Down syndrome (fetal NT, free β‐hCG and PAPP‐A). Correction for this effect in women who smoke might improve the effectiveness of first‐trimester screening for Down syndrome in these women. The underlying mechanism(s) relating smoking to the changes in first‐trimester markers require further studies.
Misoprostol for treatment of incomplete abortion at the regional hospital level: results from Tanzania
Authors: Shwekerela B , Kalumuna R , Kipingili R , Mashaka N , Westheimer E , Clark W , Winikoff B
Published: September 2007

Objective  To investigate the safety, efficacy, and acceptability of misoprostol versus manual vacuum aspiration (MVA) for treatment of incomplete abortion.

Design  A prospective open‐label randomised trial.

Setting  Kagera Regional Hospital, Bukoba, Tanzania.

Sample  Three hundred women with a clinical diagnosis of incomplete abortion and a uterine size <12 weeks.

Methods  A total of 150 women were randomised to either a single dose of 600 micrograms of oral misoprostol or MVA. If abortion was clinically complete at 7‐day follow up, the woman was released from the study. If it was still incomplete, the woman was offered the choice of an additional 1‐week follow up or immediate MVA. Cases still incomplete after a further week were offered MVA.

Main outcome measures  Incidence of successful abortion (success defined as no secondary surgical intervention provided), incidence of adverse effects, patient satisfaction.

Results  Success was very high in both arms (misoprostol: 99%; MVA: 100%; difference not significant). Most adverse effects were higher in the misoprostol arm, although the mean pain score was higher in the MVA arm (3.0 versus 3.5; P < 0.001). More women were very satisfied with misoprostol (75%) than with MVA (55%, P= 0.001), and a higher proportion of women in the misoprostol arm said that they would recommend the treatment to a friend (95% versus 75%, P < 0.001).

Conclusion  Misoprostol is as effective as MVA at treating incomplete abortion at uterine size of <12 weeks. The acceptability of misoprostol appears higher. Given the many practical advantages of misoprostol over MVA in low‐resource settings, misoprostol should be more widely available for treatment of incomplete abortion in the developing world.
Autonomic dysfunction in HIV patients on antiretroviral therapy: studies of heart rate variability
Authors: Lebech Anne‐Mette , Kristoffersen Ulrik Sloth , Mehlsen Jesper , Wiinberg Niels , Petersen Claus Leth , Hesse Birger , Gerstoft Jan , Kjaer Andreas
Published: September 2007

Background:  The presence of autonomic dysfunction in HIV patients is largely unknown. Early studies found autonomic dysfunction in patients with AIDS. Introduction of highly active antiretroviral combination therapy (ART) has dramatically changed the course of the disease and improved prognosis and decreased morbidity. At present it is not known whether introduction of ART also has decreased autonomic dysfunction.

Aim:  To evaluate whether autonomic dysfunction is present in an ART‐treated HIV population.

Methods:  HIV patients receiving ART for at least 3 years (n = 16) and an age‐matched control group of healthy volunteers (n = 12) were included. All were non‐smokers, non‐diabetic and had never received medication for dyslipidaemia or hypertension. Following a 10 min resting period a 5 min ECG recording was performed. Heart rate variability (HRV) analysis was performed in accordance with current guidelines and data reported as median (interquartile range).

Results:  The resting heart rate was higher in HIV patients compared with controls [69 (62–74) versus 57 (52–60); P<0·001]. Total HRV measured as standard deviation of normal‐to‐normal (SONN) was lower in the HIV group compared with the controls [36 (25–55) versus 74 (57–84) ms; P<0·01] as was parasympathetic activity measured as square root of the mean squared difference of successive normal‐to‐normal intervals (RMSSD) [22 (9–30) versus 35 (24–62) ms; P<0·05]. Low frequency power was lower in the HIV group compared with the control group [294 (161–602) versus 946 (711–1668) ms2; P<0·01]. High frequency power as well as systolic and diastolic blood pressure did not differ between the groups.

Conclusions:  The HIV patients in ART have increased resting heart rate and decreased short‐term heart rate variability indicating parasympathetic dysfunction.
A Randomized, Double‐Blind, Placebo‐Controlled Parallel‐Group Study to Assess the Efficacy and Safety of Nebivolol, a Novel β‐Blocker, in Patients With Mild to Moderate Hypertension
Authors: Weiss Robert J. , Weber Michael A. , Carr Albert A. , Sullivan Will A.
Published: September 2007

This double‐blind, multicenter, randomized placebo‐controlled study evaluated the antihypertensive efficacy and safety of nebivolol, a selective β1‐adrenoreceptor blocker with vasodilating effects, in patients with mild to moderate hypertension (sitting diastolic blood pressure [SiDBP] ≥95 mm Hg and ≤109 mm Hg). A total of 909 patients were randomized to receive placebo or nebivolol 1.25, 2.5, 5, 10, 20, or 40 mg once daily for up to 84 days. The primary end point was the change in trough SiDBP from baseline to study end. Nebivolol significantly reduced trough SiDBP (8.0–11.2 mm Hg compared with 2.9 mm Hg with placebo; P<.001) and trough sitting systolic blood pressure (a 4.4–9.5‐mm Hg decrease compared with a 2.2‐mm Hg decrease with placebo; P≤.002). The overall adverse event experience was similar in the nebivolol (46.1%) and placebo (40.7%) groups (P=.273). Once‐daily nebivolol is an effective antihypertensive in mild to moderate hypertensive patients.
Effects of Initial Antihypertensive Drug Class on Patient Persistence and Compliance in a Usual‐Care Setting in the United States
Authors: Patel Bimal V. , Remigio‐Baker Rosemay A. , Mehta Devi , Thiebaud Patrick , Frech‐Tamas Feride , Preblick Ronald
Published: September 2007

Antihypertensive treatment regimen persistence and compliance were measured using a retrospective cohort study of pharmacy claims data. Newly treated patients receiving monotherapy with angiotensin II receptor blockers (ARBs), angiotensin‐converting enzyme inhibitors (ACEIs), calcium channel blockers (CCBs), β‐blockers (BBs), or diuretics were followed for 1 year (N=242,882). A higher proportion of ARB patients (51.9%) were persistent in taking prescribed medication compared with those in the ACEI (48.0%), BB (40.3%), CCB (38.3%), and diuretic groups (29.9%). Compared with patients receiving diuretics, those receiving ARBs (hazard ratio [HR], 0.593; P<.0001), ACEIs (HR, 0.640; P<.0001), CCBs (HR, 0.859; P<.0001), and BBs (HR, 0.819; P<.0001) were all less likely to discontinue therapy. Compliance was similar in ACEI and ARB patients, but patients receiving ARBs and ACEIs had better compliance than those receiving BBs, CCBs, or diuretics. The lesser degree of compliance and persistence observed in patients receiving diuretics compared with other antihypertensive medications may have public health as well as cost implications.
The Use of Renin Inhibitors in the Management of Hypertension
Authors: Moser Marvin , Izzo Joseph L. , Sica Domenic A.
Published: September 2007

During a meeting of the American Society of Hypertension, an expert panel was convened to discuss the use of renin inhibitors in the management of hypertension. Marvin Moser, MD, of the Yale University School of Medicine, New Haven, CT, moderated the panel, which included Domenic A. Sica, MD, Virginia Commonwealth University Health System, Richmond, VA, and Joseph L. Izzo Jr, MD, State University of New York, Buffalo, NY. This expert panel discussion was supported by Novartis and each author received an honorarium from Novartis for time and effort spent participating in the discussion and reviewing the transcript for important intellectual content prior to publication. The authors maintained full control of the discussion and the resulting content of this article; Novartis had no input in the choice of topic, speakers, or content.
Effects of Changing Blood Viscosity and Heart Rate on Vena Contracta Width as Evaluated by Color Doppler Flow Mapping. An In Vitro Study with a Pulsatile Flow Model
Authors: Schmidt André , Da Silva Júnior Telêmaco , Pazin‐Filho Antônio , Otávio Murta Júnior Luiz , César Almeida‐Filho Oswaldo , Gallo‐Júnior Lourenço , Antonio Marin‐Neto José , Carlos Maciel Benedito
Published: September 2007

Background: There is only limited knowledge on how the quantification of valvular regurgitation by color Doppler is affected by changing blood viscosity. This study was designed to evaluate the effect of changing blood viscosity on the vena contracta width using an in vitro model of valvular insufficiency capable of providing ample variation in the rate and stroke volume. Methods: We constructed a pulsatile flow model filled with human blood at varying hematocrit (15%, 35%, and 55%) and corresponding blood viscosity (blood/water viscosity: 2.6, 4.8, 9.1) levels in which jets were driven through a known orifice (7 mm2) into a 110 mL compliant receiving chamber (compliance: 2.2 mL/mmHg) by a pulsatile pump. In addition, we used variable pump stroke volumes (5, 7.5, and 10 mL) and rates (40, 60, and 80 ppm). Vena contracta region was imaged using a 3.5 MHz transducer. Pressure and volume in the flow model were kept constant during each experimental condition, as well as ultrasound settings. Results: Blood viscosity variation in the experimental range did not induce significant changes in vena contracta dimensions. Also, vena contracta width did not change from normal to low hematocrit and viscosity levels. A very modest increase only in vena contracta dimension was observed at very high level of blood viscosity when hematocrit was set to 55% . Pump rate, in the evaluated range, did not influence vena contracta width. These results in controlled experimental settings suggest that the vena contracta is an accurate quantitative method for quantifying valvular regurgitation even when this condition is associated with anemia, a frequent finding in patients with valvular heart disease.
CASE REPORTS: Transcatheter Closure of Ruptured Sinus of Valsalva Aneurysm and Secundum Atrial Septal Defect with Limited Inferior Rim
Authors: Cui Wei , Van Bergen Andrew H. , Patel Dhaval , Javois Alex J. , Roberson David A.
Published: September 2007

We report a case of a 33‐year‐old man with Down syndrome and ruptured sinus of Valsalva aneurysm (SOVA) plus large ostium secundum atrial septal defect (ASD) with attenuated inferior rim. He underwent successful transcatheter closure of both defects at two separate procedures with transesophageal echocardiography (TEE) guidance. The combination of these two procedures has not been previously reported. Transgastric echocardiographic views which mimic transthoracic subcostal echocardiographic views provide high quality useful images of the anatomy, hemodynamics, and device placement.
The Feasibility of Tissue Doppler Acceleration as a New Predictor of Thrombogenesis in the Left Atrial Appendage Associated with Nonvalvular Atrial Fibrillation
Authors: Takahashi Noboru , Nakamura Yoichi , Komatsu Sumio , Kusano Kengo F. , Ohe Tohru
Published: September 2007

Background: Tissue acceleration utilizing the tissue Doppler imaging (TDI) technique is a new marker of ventricular contraction. We evaluated whether the left atrial appendage (LAA) wall acceleration was associated with thrombosis in patients with nonvalvular atrial fibrillation (NVAF). Methods: Seven NVAF patients with thromboembolism (TE), eight without TE, and eight with normal sinus rhythm (NSR) were studied using transesophageal echocardiography. TDI was used to evaluate the LAA wall acceleration. Results: There was a decrease in the peak flow velocity in the TE group compared with the other two groups. There was greater LAA expansion in NVAF with TE groups (with TE [8.9 ± 2.1 cm2] compared with the group without TE [7.3 ± 2.8 cm2]), but the difference was not statistically significant; the difference was statistically significant compared with the NSR group (5.3 ± 1.2 cm2; P = 0.0035). The average of the continuous 40‐frames area where tissue Doppler acceleration (TDA) was >0.024 cm/sec2 was significantly lower in the TE group (0.12 ± 0.05 cm2) compared to the group without TE (0.33 ± 0.17 cm2; P = 0.0017) and NSR group (0.30 ± 0.13 cm2; P = 0.0042), although wall velocity was not significantly different comparing the two NVAF groups. Furthermore, peak flow velocity of LAA was well correlated with LAA wall acceleration (r = 0.864, P < 0.0001). Conclusions: LAA wall acceleration obtained utilizing the TDI technique may be a new predictor of thrombogenesis in patients with NVAF.
Angiographic No‐Reflow Phenomenon and Plaque Characteristics by Virtual Histology Intravascular Ultrasound in Patients with Acute Myocardial Infarction
Authors: NAKAMURA TOMOHIRO , KUBO NORIFUMI , AKO JUNYA , MOMOMURA SHIN‐ICHI
Published: September 2007

Objective:
This study aimed to evaluate the relationship between the occurrence of the angiographic no‐reflow phenomenon in patients with acute myocardial infarction (AMI) and the preintervention plaque composition as assessed by virtual histology intravascular ultrasound (VH‐IVUS).

Background:
The angiographic no‐reflow phenomenon is an adverse prognostic factor in patients with AMI.

Method:
We enrolled consecutive 50 patients with ST‐elevation AMI was treated by primary stent implantation. All culprit lesions were imaged by VH‐IVUS before stent implantation. The angiographic no‐reflow phenomenon was defined as a decrease in final TIMI flow grade compared with TIMI flow grade before stent implantation.

Results: Eight of 50 patients developed angiographic no‐reflow after stent implantation. Gray‐scale intravascular ultrasound (IVUS) showed significantly larger external elastic membrane volume and plaque burden in the no‐reflow group. VH‐IVUS showed a trend toward larger percentage of fibro‐fatty plaque volume in the no‐reflow group than in the reflow group (23.1 ± 3.5 vs. 17.0 ± 1.1%, P = 0.05). The presence of “marble”‐like image, mainly consisting of fibro‐fatty and fibrous plaque (plaque volume of fibro‐fatty + fibrous >80% and containing fibro‐fatty plaque volume >10%) was associated with angiographic no‐reflow (P = 0.02). Corrected TIMI frame counts of the cases with “marble”‐like image were significantly larger than the cases without it (46.8 ± 5.6 vs. 27.4 ± 2.3, P = 0.01).

Conclusion:
The culprit lesions with large plaque burden, or with “marble”‐like image by VH‐IVUS, are associated with the angiographic no‐reflow phenomenon in patients with AMI.
Initial Experience with Alcohol Septal Ablation Using a Novel Magnetic Navigation System
Authors: BUERGLER JOHN M. , ALAM SHAHED , SPENCER WILLIAM , KLEIMAN NEAL S. , MELENDEZ YELENA , FRANKLIN JENNIFER , NAGUEH SHERIF F.
Published: September 2007

Objectives:
We compared the use of magnetically assisted intervention (MAI) with conventional guidewire techniques to perform alcohol septal ablation (ASA) in patients with hypertrophic obstructive cardiomyopathy (HOCM).

Background:
Treatment of symptomatic patients with HOCM using ASA has been established as an effective therapy. However, in many cases cannulaton of the septal artery can be technically challenging. Recently, a magnetically directed guidewire system has been developed to assist in navigation in difficult percutaneous interventions. By directing the guidewire to the septal branch, this system has potential to shorten the procedure time and increase success and safety of ASA in patients with HOCM.

Methods:
From October 2004 through October 2006, 44 consecutive patients underwent ASA using MAI with the Niobe® system (Stereotaxis, Inc., St. Louis, MO). We compared these patients to 29 age‐ and gradient‐matched cases using conventional techniques performed by an operator with >100 prior cases.

Results:
All procedures were successful. Both the MAI and conventional groups had improved symptoms, exercise times, and reduced gradients compared with baseline. One dissection occurred in the conventional group. Although there were no aggregate differences in acute or 3‐month clinical outcomes, the time required for guidewire cannulation of the septal branch decreased progressively with increasing experience (third tertile vs first tertile (3 [1.25–4.75 vs 10.5 [6–17] minutes, P = 0.004) compared with the conventional group (6 [2–10.25] minutes, P = 0.075 vs third tertile), suggesting a learning curve for MAI.

Conclusions:
MAI has the potential to improve wiring time and outcomes of HOCM patients undergoing ASA.
Angiographic and Procedural Correlates of Stent Thrombosis after Intracoronary Implantation of Drug‐Eluting Stents
Authors: ROY PROBAL , TORGUSON REBECCA , OKABE TERUO , SLOTTOW TINA L. PINTO , STEINBERG DANIEL H. , SMITH KIMBERLY , XUE ZHENYI , SATLER LOWELL F. , PICHARD AUGUSTO D. , WAKSMAN RON
Published: September 2007

Background:
Stent thrombosis (ST) following the implantation of drug‐eluting stents (DES) remains the major limitation of this new technology. The identification of modifiable correlates of ST may help reduce this catastrophic event.

Methods:
This was a retrospective, single‐center, lesion‐based study. A cohort of 45 consecutive lesions (35 patients) initially treated with successful DES implantation from May 2003 to February 2005 that re‐presented with ST within 12 months was identified. This cohort was compared to a control group of 1,620 unselected lesions (1,187 patients) that were successfully treated with DES implantation and which remained free of ST. Comparison of angiographic and procedural features was made between the ST and no‐ST groups, and logistic regression analysis was then performed to identify independent correlates of ST. For the purposes of the study only definite ST events (angiographically or autopsy proven) were considered.

Results:
Independent angiographic predictors of cumulative ST at 12 months were left anterior descending (LAD) artery (OR: 1.91, CI: 1.01–3.59, P = 0.045), bifurcation (OR: 2.43, CI: 1.06–5.56, P = 0.035), and in‐stent restenotic (OR: 2.64, CI: 1.12–6.25, P = 0.027) lesions. Procedural predictors were number of stents per lesion (OR: 2.30, CI: 1.29–4.11, P = 0.005) and intravascular ultrasound (IVUS) guidance (OR: 0.45, CI: 0.24–0.84, P = 0.013). Correlates of subacute events were LAD artery, proximal segment, and lack of IVUS guidance. Correlates of late ST were bifurcation and in‐stent restenotic lesions.

Conclusions:
Angiographic and procedural correlates of subacute and late ST after DES implantation differ. Lack of IVUS guidance was the only modifiable predictor identified. Treatment of bifurcation and restenotic lesions was predictive of late events.
Principal Stratification Designs to Estimate Input Data Missing Due to Death
Authors: Frangakis Constantine E. , Rubin Donald B. , An Ming‐Wen , MacKenzie Ellen
Published: September 2007

Summary We consider studies of cohorts of individuals after a critical event, such as an injury, with the following characteristics. First, the studies are designed to measure “input” variables, which describe the period before the critical event, and to characterize the distribution of the input variables in the cohort. Second, the studies are designed to measure “output” variables, primarily mortality after the critical event, and to characterize the predictive (conditional) distribution of mortality given the input variables in the cohort. Such studies often possess the complication that the input data are missing for those who die shortly after the critical event because the data collection takes place after the event. Standard methods of dealing with the missing inputs, such as imputation or weighting methods based on an assumption of ignorable missingness, are known to be generally invalid when the missingness of inputs is nonignorable, that is, when the distribution of the inputs is different between those who die and those who live. To address this issue, we propose a novel design that obtains and uses information on an additional key variable—a treatment or externally controlled variable, which if set at its “effective” level, could have prevented the death of those who died. We show that the new design can be used to draw valid inferences for the marginal distribution of inputs in the entire cohort, and for the conditional distribution of mortality given the inputs, also in the entire cohort, even under nonignorable missingness. The crucial framework that we use is principal stratification based on the potential outcomes, here mortality under both levels of treatment. We also show using illustrative preliminary injury data that our approach can reveal results that are more reasonable than the results of standard methods, in relatively dramatic ways. Thus, our approach suggests that the routine collection of data on variables that could be used as possible treatments in such studies of inputs and mortality should become common.
Ability of oral bacteria to induce tissue‐destructive molecules from human neutrophils
Authors: Shin J , Ji S , Choi Y
Published: September 2007

Aim:  The induction of tissue‐destructive molecules from neutrophils by periodontopathic bacteria has been suggested as one of the mechanisms of periodontal destruction. The aim of this study was to determine whether the ability to stimulate neutrophils is an authentic characteristic of periodontopathic bacteria.

Methods:  We evaluated, along with phagocytosis, the production of reactive oxygen species (ROS), matrix metalloproteinase‐8 (MMP‐8), and interleukin‐1β by neutrophils in response to non‐periodontopathic Streptococcus sanguinis and periodontopathic bacteria Fusobacterium nucleatum and Treponema denticola, in the absence or presence of antibodies. Phagocytosis, the death of neutrophils, and intracellular ROS production were measured by flow cytometry and the concentrations of MMP‐8 and interleukin‐1β secreted into medium were determined by enzyme‐linked immunosorbent assay.

Results:  S. sanguinis and F. nucleatum induced greater production of ROS, MMP‐8, and interleukin‐1β than did T. denticola. The levels of tissue‐destructive molecules produced by neutrophils had a positive correlation with phagocytosis. Opsonization of bacteria with antibodies significantly increased phagocytosis and ROS production and release, thus increasing both bacterial clearance and potential tissue damage.

Conclusion:  The ability of oral bacteria to induce tissue‐destructive molecules from neutrophils is not an inherent characteristic of periodontopathic bacteria, which would provide a new insight into the role of neutrophils in periodontal destruction.
Survey regarding the status of senior physicians in German dermatology clinics
Authors: Mrowietz Ulrich , Rott Silja
Published: September 2007

The group of senior physicians/assistant medical directors between chairman and residents is in a major focus regarding current changes in the medical system in Germany. The manifold clinical tasks clearly underline the importance of senior physicians as key players; they are neither so regarded nor paid accordingly. In addition senior physicians are responsible for education of residents. To gain insight into the current situation of senior physicians in dermatology information was acquired by a detailed questionnaire. The return‐rate of 44.7% was considerably higher than in comparable surveys. The responses show a high degree of satisfaction with medical work, position and interaction with chairman and staff. Most critical was the increasing administrative work and the low salary.

This is the first survey in a medical subspecialty among senior physicians in Germany. After the planned new pay schedule is instituted and restructuring of professorships in academic institutions is completed, the survey will be repeated.
Association of TLR2 gene Arg753Gln polymorphism with urinary tract infection in children
Authors: Tabel Y. , Berdeli A. , Mir S.
Published: September 2007

The aim of this study is to investigate Arg753Gln allele polymorphisms of toll‐like receptor‐2 (TLR2) gene distribution, allele frequency in urinary tract infection (UTI) and genotype–phenotype association of TLR2 gene in children with UTI. The polymorphism was investigated in 124 children with UTI (22 boys and 102 girls; mean age 5.81 ± 3.47 years) with direct DNA sequencing‐based method. TLR2 gene Arg753Gln allele frequency was higher in the patient group when compared with control group (OR 3.14, 95%CI 1.53–6.44, P < 0.001). The frequency of the Arg753Gln allele was significantly higher in gram‐positive group than in gram‐negative group (OR 7.64, 95%CI 2.80–20.81, P < 0.001). The frequency of UTI was found significantly higher in the Arg753Gln allele carriers of TLR2 gene than the non‐carriers (OR 4.94, 95%CI 1.09–22.33, P < 0.05). Similarly, the incidence of asymptomatic UTI was also found significantly higher in the group carrying Arg753Gln allele (OR 3.73, 95%Cl 1.54–9.04, P < 0.05). As a result, we suggest that TLR2 gene could be the predisposing factor for urinary tract infection. Additionally, we observed that subjects carrying the TLR2 Arg753Gln allele had higher risk of urinary tract infection with gram‐positive pathogens, history of more than two attacks of UTI and asymptomatic UTI.
The polymorphism and haplotype analysis of HLA‐A, ‐B and ‐DRB1 genes of population in Jiangsu province of China
Authors: Miao K. R. , Pan Q. Q. , Tang R. C. , Zhou X. P. , Fan S. , Wang X. Y. , Zhao X. , Xue M. , Zhou X. Y. , Wang C. Y.
Published: September 2007

The polymorphism of human leucocyte antigen (HLA)‐A, ‐B and ‐DRB1 genes and their computed haplotype analysis results from a population of Jiangsu province of China are presented here. The data consist of 20 248 unrelated peripheral blood stem cell donors in Jiangsu Branch of Chinese National Marrow Donor Program registry. In total, 18 different HLA‐A alleles, 34 different HLA‐B alleles and 13 different HLA‐DRB1 alleles were found in Jiangsu Han population. The most frequent alleles in HLA‐A, ‐B and ‐DRB1 loci were A*02 (29.55%), B*15 (14.40%), and DRB1*09 (16.15%), respectively. The most common haplotype in A‐B‐DRB1 loci was A*30‐B*13‐ DRB1*07 (6.92%), in A‐B loci was A*30‐B*13 (8.05%), in B‐DRB1 loci was B*13‐DRB1*07 (8.17%), and in A‐DRB1 loci was A*02‐DRB1*09 (8.30%). The dendrogram study indicated that the distribution of HLA genes in Jiangsu Han population, as expected, represented a mixture of Northern and Southern Han population in China. These findings could shade new lights in population genetics and anthropology studies of Han‐Chinese.
Mitigating selection in HLA‐B27 not confirmed
Authors: Müller B. , Pavesio C. , Eggert M. , Neek G. , Mitchison N.
Published: September 2007

The existence of a small, discrete group of HLA‐B27 promoters, potentially able to mitigate the deleterious effect of this allele, has not been confirmed.
Effect of Caspofungin on Metabolite Profiles of
Aspergillus
Species Determined by Nuclear Magnetic Resonance Spectroscopy
Authors: Plummer R. , Bodkin J. , Power D. , Pantarat N. , Bubb W. A. , Kuchel P. W. , Sorrell T. C.
Published: September 2007

Invasive aspergillosis remains a potentially life-threatening infection, the incidence of which is increasing. Current methods used to determine the susceptibilities of
Aspergillus
strains to antifungal drugs are often unreliable. Nuclear magnetic resonance (NMR) spectroscopy can identify the metabolic complement of microorganisms while monitoring nutrient utilization from the incubation medium. We used 600-MHz
1
H NMR spectroscopy to monitor the metabolic responses of five
Aspergillus
species cultured in RPMI 1640-2% glucose-morpholinepropanesulfonate buffer to various concentrations of the antifungal drugs amphotericin B (AMB) and caspofungin. The metabolic endpoint (MEP) was determined from nutrient and metabolite resonances, measured as a function of the drug concentration, and was defined as a ≥50% reduction in nutrient consumption or metabolite production. MICs were evaluated by a modification of Clinical and Laboratory Standards Institute broth microdilution method M27-A, and minimal effective concentrations (MECs) were determined by microscopic examination of fungal hyphae. For AMB, the MEPs coincided with the MICs. For caspofungin, the MEPs agreed with the MECs for several
Aspergillus
strains, but the effect of drug pressure was more complex for others. Expansion of the MEP definition to include any significant changes in metabolite production resulted in agreement with the MEC in most cases. Paradoxical metabolic responses were observed for several
Aspergillus
strains at either high or low caspofungin concentrations and for one
Aspergillus terreus
strain with AMB. NMR spectroscopy proved to be a powerful tool for detecting the subtle effects of drug pressure on fungal metabolism and has the potential to provide an alternative method for determining the susceptibilities of
Aspergillus
species to antifungal drugs.
Effects of Serum on In Vitro Susceptibility Testing of Echinocandins
Authors: Odabasi Zekaver , Paetznick Victor , Rex John H. , Ostrosky-Zeichner Luis
Published: September 2007

The effects of protein binding on the activities of caspofungin, anidulafungin, and micafungin were evaluated againstCandidaandAspergillusspecies. Adding human serum sharply increased the MICs of micafungin and anidulafungin and modestly affected the MIC of caspofungin. The increase in MICs does not appear consistent with the rate of protein binding for the three compounds.
Protective Properties and Surface Localization ofPlasmodium falciparumEnolase
Authors: Pal-Bhowmick Ipsita , Mehta Monika , Coppens Isabelle , Sharma Shobhona , Jarori Gotam K.
Published: September 2007

The enolase protein of the human malarial parasitePlasmodium falciparumhas recently been characterized. Apart from its glycolytic function, enolase has also been shown to possess antigenic properties and to be present on the cell wall of certain invasive organisms, such asCandida albicans. In order to assess whether enolase ofP. falciparumis also antigenic, sera from residents of a region of Eastern India where malaria is endemic were tested against the recombinantP. falciparumenolase (r-Pfen) protein. About 96% of immune adult sera samples reacted with r-Pfen over and above the seronegative controls. Rabbit anti-r-Pfen antibodies inhibited the growth of in vitro cultures ofP. falciparum. Mice immunized with r-Pfen showed protection against a challenge with the 17XL lethal strain of the mouse malarial parasitePlasmodium yoelii. The antibodies raised against r-Pfen were specific forPlasmodiumand did not react to the host tissues. Immunofluorescence as well as electron microscopic examinations revealed localization of the enolase protein on the merozoite cell surface. These observations establish malaria enolase to be a potential protective antigen.
Direct Microscopic Quantification of Dynamics of
Plasmodium berghei
Sporozoite Transmission from Mosquitoes to Mice
Authors: Jin Yamei , Kebaier Chahnaz , Vanderberg Jerome
Published: September 2007

The number of malaria sporozoites delivered to a host by mosquitoes is thought to have a significant influence on the subsequent course of the infection in the mammalian host. We did studies with
Anopheles stephensi
mosquitoes with salivary gland infections of
Plasmodium berghei
sporozoites expressing a red fluorescent protein. After individual mosquitoes fed on an ear pinna or the ventral abdomen of a mouse, fluorescence microscopy was used to count numbers of sporozoites. Mosquitoes allowed to feed on the ear for periods of 3 versus 15 min deposited means of 281 versus 452 sporozoites, respectively, into the skin; this may have epidemiological implications because mosquitoes can feed for longer periods of time on sleeping hosts. Mosquitoes feeding on the ventral abdomen injected sporozoites not only into the skin but also into the underlying peritoneal musculature. Although mosquitoes injected fewer sporozoites into the abdominal tissues, more of these were reingested into the mosquito midgut, probably a consequence of easier access to blood intake from the abdominal area. The most consistent parameter of sporozoite transmission dynamics under all conditions of mosquito probing and feeding was the relatively slow release rate of sporozoites (∼1 to 2.5 per second) from the mosquito proboscis. The numbers of sporozoites introduced into the host by mosquitoes and the transmission efficiencies of sporozoite delivery are multifactorial phenomena that vary with length of probing time, skin site being fed upon, and numbers of sporozoites within the salivary glands.
Roles of Serine Accumulation and Catabolism in the Colonization of the Murine Urinary Tract by
Escherichia coli
CFT073
Authors: Anfora Andrew T. , Haugen Brian J. , Roesch Paula , Redford Peter , Welch Rodney A.
Published: September 2007

A
d
-serine deaminase (DsdA) mutant of uropathogenic
Escherichia coli
strain CFT073 has a hypercolonization phenotype in a murine model of urinary tract infection (UTI) due to increased virulence gene expression by an unknown mechanism (B. J. Haugen et al., Infect. Immun. 75:278-289, 2007). DsdC is a
d
-serine-dependent activator of
dsdXA
transcription. DsdC may regulate the virulence genes responsible for hypercolonization. The loss of DsdA leads to increased intracellular accumulation of
d
-serine. In this study we show that deletion of the genes encoding
l
-serine deaminases SdaA and SdaB resulted in a mutant that accumulates higher intracellular levels of
l
-serine than CFT073. CFT073
sdaA sdaB
has a mild competitive colonization defect whereas a CFT073
dsdA sdaA sdaB
triple mutant shows a greater loss in competitive colonization ability. Thus, the inability to generate serine-specific catabolic products does not result in hypercolonization and the ability to catabolize serine represents a positive physiological trait during murine UTI. CFT073
dsdC
and CFT073
dsdC dsdA
mutants continue to outcompete the wild type in the UTI model. These results confirm that loss of DsdA activity results in the hypercolonization phenotype and that DsdC does not play a direct role in the elevated-colonization phenotype. Interestingly, a CFT073
dsdA
mutant with deletions of
d
-serine transporter genes
dsdX
and
cycA
shows wild-type colonization levels of the bladder but is attenuated for kidney colonization. Thus,
d
-serine acts as a signal for hypercolonization and virulence gene expression by CFT073
dsdA
, whereas overall catabolism of serine represents a positive
Escherichia coli
fitness trait during UTI.
Relative Contributions of
Enterococcus faecalis
OG1RF Sortase-Encoding Genes,
srtA
and
bps
(
srtC
), to Biofilm Formation and a Murine Model of Urinary Tract Infection
Authors: Kemp Kelvin D. , Singh Kavindra V. , Nallapareddy Sreedhar R. , Murray Barbara E.
Published: September 2007

Deletion mutants of the two sortase genes of
Enterococcus faecalis
OG1RF were constructed.
srtC
(renamed here
bps
for
b
iofilm and
p
ilus-associated
s
ortase) was previously shown to be necessary for the production of Ebp pili and important for biofilm formation and endocarditis. Here, we report that a
srtA
deletion mutant showed a small (5%) yet significant (
P
= 0.037) reduction in biofilm relative to OG1RF, while a Δ
srtA
Δ
bps
double mutant showed a much greater reduction (74% versus OG1RF and 44% versus the Δ
bps
mutant). In a murine urinary tract infection (UTI), the 50% infective doses of both the Δ
srtA
Δ
bps
and Δ
bps
mutants were ∼2 log
10
greater than that of OG1RF or the Δ
srtA
mutant. Similarly, ∼2 log
10
fewer bacteria were recovered from the kidneys after infection with the Δ
bps
mutant (
P
= 0.017) and the Δ
srtA
Δ
bps
double mutant (
P
= 0.022) compared to wild-type strain OG1RF. In a competition UTI, the Δ
bps
mutant was slightly, but not significantly, less attenuated than the Δ
srtA
Δ
bps
double mutant. Fluorescence-activated cell sorter analysis with Ebp-specific antibodies confirmed that a minority of OG1RF cells express Ebp pili on their surface in vitro and that Bps has a major role in Ebp pilus biogenesis but also indicated a function for SrtA in surface localization of the pilus subunit protein EbpA. In conclusion, deletion of
bps
had a major effect on virulence in murine UTIs, as well as biofilm; deletion of
srtA
from OG1RF had little effect on these phenotypes, but its deletion from a
bps
mutant had a pronounced effect on biofilm, suggesting that Bps and/or the proteins it anchors may compensate for the loss of some SrtA function(s).
Recombinant Exosporium Protein BclA of
Bacillus anthracis
Is Effective as a Booster for Mice Primed with Suboptimal Amounts of Protective Antigen
Authors: Brahmbhatt Trupti N. , Darnell Stephen C. , Carvalho Humberto M. , Sanz Patrick , Kang Tae J. , Bull Robert L. , Rasmussen Susan B. , Cross Alan S. , O'Brien Alison D.
Published: September 2007

Bacillus collagen-like protein of anthracis (BclA) is an immunodominant glycoprotein located on the exosporium of
Bacillus anthracis
. We hypothesized that antibodies to this spore surface antigen are largely responsible for the augmented immunity to anthrax that has been reported for animals vaccinated with inactivated spores and protective antigen (PA) compared to vaccination with PA alone. To test this theory, we first evaluated the capacity of recombinant, histidine-tagged, nonglycosylated BclA (rBclA) given with adjuvant to protect A/J mice against 10 times the 50% lethal dose of Sterne strain spores introduced subcutaneously. Although the animals elicited anti-rBclA antibodies and showed a slight but statistically significant prolongation in the mean time to death (MTD), none of the mice survived. Similarly, rabbit anti-rBclA immunoglobulin G (IgG) administered intraperitoneally to mice before spore inoculation increased the MTD statistically significantly but afforded protection to only 1 of 10 animals. However, all mice that received suboptimal amounts of recombinant PA and that then received rBclA 2 weeks later survived spore challenge. Additionally, anti-rBclA IgG, compared to anti-PA IgG, promoted a sevenfold-greater uptake of opsonized spores by mouse macrophages and markedly decreased intramacrophage spore germination. Since BclA has some sequence similarity to human collagen, we also tested the extent of binding of anti-rBclA antibodies to human collagen types I, III, and V and found no discernible cross-reactivity. Taken together, these results support the concept of rBclA as being a safe and effective boost for a PA-primed individual against anthrax and further suggest that such rBclA-enhanced protection occurs by the induction of spore-opsonizing and germination-inhibiting antibodies.
Distribution and Physiology of ABC-Type Transporters Contributing to Multidrug Resistance in Bacteria
Authors: Lubelski Jacek , Konings Wil N. , Driessen Arnold J. M.
Published: September 2007

Membrane proteins responsible for the active efflux of structurally and functionally unrelated drugs were first characterized in higher eukaryotes. To date, a vast number of transporters contributing to multidrug resistance (MDR transporters) have been reported for a large variety of organisms. Predictions about the functions of genes in the growing number of sequenced genomes indicate that MDR transporters are ubiquitous in nature. The majority of described MDR transporters in bacteria use ion motive force, while only a few systems have been shown to rely on ATP hydrolysis. However, recent reports on MDR proteins from gram-positive organisms, as well as genome analysis, indicate that the role of ABC-type MDR transporters in bacterial drug resistance might be underestimated. Detailed structural and mechanistic analyses of these proteins can help to understand their molecular mode of action and may eventually lead to the development of new strategies to counteract their actions, thereby increasing the effectiveness of drug-based therapies. This review focuses on recent advances in the analysis of ABC-type MDR transporters in bacteria.
Regulation of Vacuolar pH and Its Modulation by Some Microbial Species
Authors: Huynh Kassidy K. , Grinstein Sergio
Published: September 2007

To survive within the host, pathogens such asMycobacterium tuberculosisandHelicobacter pylorineed to evade the immune response and find a protected niche where they are not exposed to microbicidal effectors. The pH of the microenvironment surrounding the pathogen plays a critical role in dictating the organism's fate. Specifically, the acidic pH of the endocytic organelles and phagosomes not only can affect bacterial growth directly but also promotes a variety of host microbicidal responses. The development of mechanisms to avoid or resist the acidic environment generated by host cells is therefore crucial to the survival of many pathogens. Here we review the processes that underlie the generation of organellar acidification and discuss strategies employed by pathogens to circumvent it, usingM. tuberculosisandH. pylorias examples.
Genomics ofActinobacteria: Tracing the Evolutionary History of an Ancient Phylum
Authors: Ventura Marco , Canchaya Carlos , Tauch Andreas , Chandra Govind , Fitzgerald Gerald F. , Chater Keith F. , van Sinderen Douwe
Published: September 2007

Actinobacteriaconstitute one of the largest phyla amongBacteriaand represent gram-positive bacteria with a high G+C content in their DNA. This bacterial group includes microorganisms exhibiting a wide spectrum of morphologies, from coccoid to fragmenting hyphal forms, as well as possessing highly variable physiological and metabolic properties. Furthermore,Actinobacteriamembers have adopted different lifestyles, and can be pathogens (e.g.,Corynebacterium,Mycobacterium,Nocardia,Tropheryma, andPropionibacterium), soil inhabitants (Streptomyces), plant commensals (Leifsonia), or gastrointestinal commensals (Bifidobacterium). The divergence ofActinobacteriafrom other bacteria is ancient, making it impossible to identify the phylogenetically closest bacterial group toActinobacteria. Genome sequence analysis has revolutionized every aspect of bacterial biology by enhancing the understanding of the genetics, physiology, and evolutionary development of bacteria. Various actinobacterial genomes have been sequenced, revealing a wide genomic heterogeneity probably as a reflection of their biodiversity. This review provides an account of the recent explosion of actinobacterial genomics data and an attempt to place this in a biological and evolutionary context.