bluuebunny/crossref_metadata_2025 huggingface dataset:
The Nance Obturator, a New Fixed Obturator for Patients with Cleft Palate and Fistula
Authors: Borzabadi‐Farahani Ali , Groper John N. , Tanner Aaron M. , Urata Mark M. , Panossian Andre , Yen Stephen L.‐K.
Published: June 2012

In patients with fistulas that impair function (e.g., feeding, resonance, intelligibility), obturators are used to improve feeding and reduce nasal air emission by occluding the abnormal opening between the oral and nasal cavities. This report describes a novel method for occluding an anterior palatal fistula in patients with cleft palates. The new design for a fixed obturator is based on the Nance appliance, which was originally used as a space maintainer, but has been redesigned for closing an anterior palatal fistula in a patient with cleft lip and palate. The Nance obturator may be used when the surgical closure of the fistula is not feasible and a removable device is not successful. As it is a fixed device, it does not require remaking with maxillary growth. The new design may also function as a fixed space maintainer to preserve molar anchorage and maxillary transverse width.
Rise in ICD Shock Impedance: Lead Fracture or Death?
Authors: STROOBANDT ROLAND X. , Van HEUVERSWYN FREDERIC E. , KUCHER ANDREAS , BAROLD S. SERGE
Published: June 2012

Background: Remote monitoring allows for interrogation and extensive data retrieval of implantable cardioverter‐defibrillators (ICDs). Data on ICD parameters at the time of death and afterwards are limited. The purpose of this retrospective study was to examine the changes in lead impedances of ICDs at the time of death and afterwards.

Methods: A total of 37 Biotronik (SE & CO. KG, Berlin, Germany) ICDs (20 ICD‐cardiac resynchronization therapy, 16 dual‐chamber ICDs, and one single‐chamber ICD), retrieved after death, were interrogated. Stored intracardiac electrograms were analyzed to determine the cause of death. Impedance trend curves of shock and pacing lead impedances were analyzed and correlated retrospectively with the reported time of death. The influence of cold exposure on lead impedances was tested in three other single‐chamber Biotronik ICDs.

Results: Of 37 patients, the cause of death was due to ventricular tachyarrhythmias in 21 patients. In 12 patients, death was not arrhythmia‐related. In four patients, the cause of death could not be determined due to overwriting of the episodes at the time of death. A significant increase of shock and pacing lead impedances was observed in the postmortem days (P < 0.001 for all lead impedances). All lead impedance values increased significantly within the first postmortem day (P < 0.001 for all lead impedances). Cold exposure decreased shock lead impedance but did not affect pacing lead impedance.

Conclusion: Postmortem analysis of ICDs allows tracking of lead impedance changes, which correlate with the day of death. The rise in postmortem impedances should not be interpreted as contributing to the mode of death. (PACE 2012; 35:1103–1110)
Catheter Ablation of Typical Atrial Flutter in Severe Pulmonary Hypertension
Authors: BRADFIELD JASON , SHAPIRO SHELLEY , FINCH WILLIAM , TUNG RODERICK , BOYLE NOEL G. , BUCH ERIC , MATHURIA NILESH , MANDAPATI RAVI , SHIVKUMAR KALYANAM , BERSOHN MALCOLM
Published: June 2012

Atrial Flutter and Pulmonary Hypertension. Background: Radiofrequency ablation is first‐line therapy for atrial flutter (AFL). There are no studies of ablation in patients with severe pulmonary arterial hypertension (PAH).

Methods:
Consecutive patients with severe PAH (systolic pulmonary artery pressure >60 mmHg) and AFL referred for ablation were evaluated. Patients with complex congenital heart disease were excluded.

Results:
A total of 14 AFL ablation procedures were undertaken in 12 patients. A total of 75% of patients were female; mean age 49 ± 12 years. SPAP prior to ablation was 99 ± 35 mmHg. Baseline 6‐minute walk distance was 295 ± 118 m. ECG demonstrated a typical AFL pattern in only 42% of cases. Baseline AFL cycle length was longer in PAH patients compared to controls (295 ± 53 ms vs 252 ± 35 ms, P = 0.006).

Cavotricuspid isthmus dependence was verified in 86% of cases. Acute success was obtained in 86% of procedures. SPAP decreased from 114 ± 44 mmHg to 82 ± 38 mmHg after ablation (P = 0.004). BNP levels were lower postablation (787 ± 832 pg/mL vs 522 ± 745 pg/mL, P = 0.02). Complications were seen in 14%. A total of 80% (8/10) of patients were free of AFL at 3 months; 75% (6/8) at 1 year.

Conclusion:
Ablation of AFL in severe PAH patients is feasible, with good short‐ and intermediate‐term success rates. The ECG pattern is not a reliable marker of isthmus dependence. The SPAP and BNP levels may decrease postablation. AFL may be a marker of poor outcomes in patients with PAH with a 1‐year mortality rate of 42% in this study. This rate is higher than expected in the general PAH population. (J Cardiovasc Electrophysiol, Vol. 23, pp. 1185–1190, November 2012)
Non‐Bayesian Inference: Causal Structure Trumps Correlation
Authors: Bes Bénédicte , Sloman Steven , Lucas Christopher G. , Raufaste Éric
Published: June 2012

The study tests the hypothesis that conditional probability judgments can be influenced by causal links between the target event and the evidence even when the statistical relations among variables are held constant. Three experiments varied the causal structure relating three variables and found that (a) the target event was perceived as more probable when it was linked to evidence by a causal chain than when both variables shared a common cause; (b) predictive chains in which evidence is a cause of the hypothesis gave rise to higher judgments than diagnostic chains in which evidence is an effect of the hypothesis; and (c) direct chains gave rise to higher judgments than indirect chains. A Bayesian learning model was applied to our data but failed to explain them. An explanation‐based hypothesis stating that statistical information will affect judgments only to the extent that it changes beliefs about causal structure is consistent with the results.
Family Life History and Late Mid‐Life Mortality in Norway
Authors: Kravdal ØYstein , Grundy Emily , Lyngstad Torkild H. , Wiik Kenneth Aa.
Published: June 2012

Using data on all Norwegians born 1935–68, we analyze the associations between mortality and a combined indicator of fertility and marital or partnership status and history. The focus is on ages 40–73 and the years 1980–2008 (30 million person‐years of observations and 117,000 deaths). Among men in first marriages, the childless have 36 percent higher mortality than those with two or more children. The corresponding figure for women is 61 percent. The never‐married have higher mortality and are differentiated even more by parenthood status. Thus, childless never‐married men and women have mortality three times as high as those who are married and have two or more children. The apparent advantage associated with having at least two children is smallest among men who divorced before their oldest child's tenth birthday. Having step‐children has no association with mortality for those without natural children but is associated with higher mortality among the parous.
Effects of AI protocol and time interval from onset of estrus to AI on conception rate in Japanese Black cows
Authors: HEMMI Koichiro , KOBAYASHI Ikuo , KAJISA Makoto , KITAHARA Go , FUKUYAMA Kiichi , HARADA Hiroshi , KAMIMURA Shunichi
Published: June 2012

Two different artificial insemination (AI) protocols were investigated to determine the effect of the time interval from the onset of estrus (as detected by a pedometer) to the AI on the conception rate in Japanese Black cows. Seventy‐three cows were divided into two groups that received AI either after the induction of synchronized ovulation (synchronized AI group; n = 26) or at the time of observed estrus (control AI group; n = 47). Each group was further divided into two subgroups, which were artificially inseminated either 0–12 h (early AI group; n = 21) or 12–24 h (late AI group; n = 52) after the onset of estrus. There was no significant difference in the conception rate between the synchronized AI and control AI groups. The AI protocol and the detection of estrus using a threshold of counted steps (as measured by a pedometer) in this study could be effective for planned reproduction management without the observation of standing estrus in Japanese Black cows.
Extended Pelvic Lymph Node Dissection Does Not Affect Erectile Function Recovery in Patients Treated with Bilateral Nerve-Sparing Radical Prostatectomy
Authors: Gandaglia Giorgio , Suardi Nazareno , Gallina Andrea , Abdollah Firas , Capitanio Umberto , Salonia Andrea , Colombo Renzo , Bianchi Marco , Chun Felix K. , Hansen Jens , Rigatti Patrizio , Montorsi Francesco , Briganti Alberto
Published: June 2012

Introduction

Extended pelvic lymph node dissection (ePLND) might be associated with damages to the pelvic plexus, potentially affecting erectile function (EF) recovery after radical prostatectomy (RP). However, the impact of the extent of pelvic lymph node dissection (PLND) on EF has never been addressed.

Aim

The aim of this study is to evaluate the impact of ePLND on potency recovery in patients who underwent bilateral nerve-sparing RP (BNSRP).

Methods

The study included 396 patients with prostate cancer treated with BNSRP by two high-volume surgeons. Patients were retrospectively divided into two groups based on PLND status: no PLND (N = 161; 40.9%) and ePLND (N = 235; 59.1%) at the time of BNSRP. All patients had preoperative functional and oncological data. Univariable and multivariable Cox regression models tested the association between ePLND and EF recovery after surgery, after accounting for confounders.

Main Outcome Measure

The International Index of Erectile Function (IIEF) was used to evaluate EF after BNSRP. Postoperative EF recovery was defined as an IIEF-EF domain score ≥22.

Results

At a mean follow up of 33.2 months after surgery (median 30), 183 patients (46.2%) recovered EF. Overall, postoperative EF recovery rate at 2 years was 48.4%. No significant differences were recorded when patients were stratified according to the extent of PLND (EF recovery rates at 2-year: 46.6% vs. 49.7% for patients who did not undergo PLND vs. those treated with ePLND; P = 0.33). These results were confirmed at multivariable analyses, where only age at surgery and preoperative IIEF-EF (all P ≤ 0.03), but not ePLND (P = 0.8), represented independent predictors of EF recovery.

Conclusions

The extent of PLND is not associated with potency after BNSRP. Conversely, other factors such as age at surgery and preoperative EF represent the major predictors of postoperative potency recovery. Therefore, when indicated, ePLND can be safely performed without compromising EF outcomes.
Potentially Bioavailable Natural Organic Carbon and Hydrolyzable Amino Acids in Aquifer Sediments
Authors: Thomas Lashun K. , Widdowson Mark A. , Novak John T. , Chapelle Francis H. , Benner Ronald , Kaiser Karl
Published: June 2012

This study evaluated the relationship between concentrations of operationally defined potentially bioavailable organic ‐carbon (PBOC) and hydrolyzable amino acids (HAAs) in sediments collected from a diverse range of chloroethene‐‐contaminated sites. Concentrations of PBOC and HAA were measured using aquifer sediment samples collected at six selected study sites. Average concentrations of total HAA and PBOC ranged from 1.96 ± 1.53 to 20.1 ± 25.6 mg/kg and 4.72 ± 0.72 to 443 ± 65.4 mg/kg, respectively. Results demonstrated a statistically significant positive relationship between concentrations of PBOC and total HAA present in the aquifer sediment (p < 0.05). Higher levels of HAA were consistently observed at sites with greater levels of PBOC and first‐order decay rates. Because amino acids are known to be readily biodegradable carbon compounds, this relationship suggests that the sequential chemical extraction procedure used to measure PBOC is a useful indicator of bioavailable carbon in aquifer sediments. This, in turn, is consistent with the interpretation that PBOC measurements can be used for estimating the amount of natural organic carbon available for driving the reductive dechlorination of chloroethenes in groundwater systems.
Hypospadias repair: the nursing contribution
Authors: Pfeil Michael , Parr Joanne , Kulkarni Milind , Mathur Azad B
Published: June 2012

The role of the urology nurse in the care of 50 boys undergoing hypospadias surgery was prospectively evaluated using semi‐structured interviews and data retrieved from hospital notes. Four nursing‐related areas of interest were identified: Firstly, that nurses were instrumental in preparing the families for surgery by assessing the boys and providing information to the families. This enabled the early discharge of the children. Secondly, that nurses also dealt with any problems arising from pain or the wound as well as from the catheter or stent. Thirdly, that named nurses provided seamless care to the families enabling a development of familiarity and trust. Finally, nurses provided routine back‐up and a 24‐h emergency call facility for the families at home. These were valued by the parents for their reassuring and confidence giving effect as well as the quality of the advice given. Based on the results of this evaluation it was recommended to establish and introduce a care pathway for day‐case hypospadias repairs and to upgrade the urology nurses' role towards advanced nursing practice.
Hoya lithophytica sp. nov. (Apocynaceae: Marsdenieae), from western Thailand
Authors: Kidyoo Manit , Watthana Santi
Published: June 2012

A new species of Hoya R. Br., Hoya lithophytica Kidyoo, has been discovered in western Thailand. Here we provide a detailed description and illustrations of this newly revealed species. It was found only on the cliff faces of limestone mountains. The new species is closely related to H. wightii Hook. f. subsp. palniensis K. T. Matthew. However, Hoya lithophytica has lateral nerves at right angles to the midrib and obovate coronal scales, but H. wightii Hook. f. subsp. palniensis has lateral nerves at acute angles to the midrib and elliptic coronal scales.
Neuromyelitis optica should be classified as an astrocytopathic disease rather than a demyelinating disease
Authors: Fujihara Kazuo , Misu Tatsuro , Nakashima Ichiro , Takahashi Toshiyuki , Bradl Monika , Lassmann Hans , Takano Rina , Nishiyama Shuhei , Takai Yoshiki , Suzuki Chihiro , Sato Douglas , Kuroda Hiroshi , Nakamura Masashi , Fujimori Juichi , Narikawa Koichi , Sato Shigeru , Itoyama Yasuto , Aoki Masashi
Published: June 2012

Neuromyelitis optica (NMO) is characterized by severe optic neuritis and transverse myelitis. The relationship of NMO to multiple sclerosis (MS) has long been debated, but NMO has been classified as a demyelinating disease. Since the discovery of an NMO‐specific autoantibody to aquaporin 4 (AQP4), a dominant water channel in the central nervous system densely expressed on end‐feet of astrocytes, the clinical, magnetic resonance imaging and laboratory findings to distinguish NMO from MS have been clarified. Furthermore, pathological studies showed an extensive loss of immunoreactivities to astrocytic proteins, AQP4 and glial fibrillary acidic protein (GFAP), and perivascular deposition of immunoglobulins and activated complements with a relative preservation of the staining of myelin basic protein (MBP) in acute NMO lesions, but not in MS. In support of these pathological findings, the GFAP levels in the cerebrospinal fluid (CSF) during acute exacerbation of NMO are remarkably elevated compared with MBP and neurofilament, whereas the CSF‐GFAP in MS is not different from those in controls. Additionally, recent experimental studies have convincingly shown that AQP4 antibody is pathogenic in causing astorocytic destruction and dysfunction in vitro, ex vivo and in vivo. These findings strongly suggest that damage of astrocytes is far more severe than those of myelin and neurons, and that autoimmune astrocytopathy is the primary pathology in NMO. Based on these accumulated data, we propose that NMO should be classified as an astrocytopathic disease rather than a demyelinating disease.
Association of on‐treatment serum hepatitis B surface antigen level with sustained virological response to nucleos(t)ide analog in patients with hepatitis B e‐antigen positive chronic hepatitis B
Authors: Kim Soon Sun , Lee Dami , Lee Myoung Hee , Cheong Jae Youn , Cho Sung Won
Published: June 2012

Aim:  This study evaluated the on‐treatment serum hepatitis B surface antigen (HBsAg) level during nucleos(t)ide analog (NUC) therapy and the correlation with off‐treatment sustained virological response (SVR).

Methods:  Fifty‐one consecutive patients with hepatitis B e‐antigen (HBeAg) positive chronic hepatitis B who achieved HBeAg loss/seroconversion after NUC therapy and completed 12 months or more of additional therapy were included. Serum HBsAg and hepatitis B virus (HBV) DNA levels were determined at baseline, 3, 6, 9 and 12 months, and at the end of treatment. SVR was defined as HBV DNA levels of less than 10 000 copies/mL until 6 or 12 months off‐treatment without reappearance of HBeAg.

Results:  Twenty‐two (43.1%) and 13 (25.5%) patients maintained SVR at 6 and 12 months off‐treatment, respectively. In univariate analyses, a decline of HBsAg of 0.5 log10 IU/mL or less at 6 months (P = 0.006) and 12 months (P = 0.013), the mean change in HBsAg level at 6 months (P = 0.024), and lamivudine or entecavir treatment (P = 0.019) were significant predictive factors for SVR at 6 months off‐treatment. A decline of HBsAg of 0.5 log10 IU/mL or less at 6 months and lamivudine or entecavir treatment were independent factors on multivariate analyses (odds ratio [OR], 16.67; 95% confidence interval [CI], 1.86–142.86 [P = 0.012]; and OR, 14.83; 95% CI, 1.18–185.73 [P = 0.036]; respectively).

Conclusion:  On‐treatment serum HBsAg level predicted early off‐treatment SVR to NUC therapy in patients infected with genotype C.
Modeling of Magnetorheological Fluids by the Discrete Element Method
Authors: Kargulewicz Mickaël , Iordanoff Ivan , Marrero Victor , Tichy John
Published: June 2012

Magnetorheological (MR) fluids are fluids whose properties vary in response to an applied magnetic field. Such fluids are typically composed of microscopic iron particles (~1-20μm diameter, 20-40% by volume) suspended in a carrier fluid such as mineral oil or water. MR fluids are increasingly proposed for use in various mechanical system applications, many of which fall in the domain of tribology, such as smart dampers and clutches, prosthetic articulations, and controllable polishing fluids. The goal of this study is to present an overview of the topic to the tribology audience, and to develop an MR fluid model from the microscopic point of view using the discrete element method (DEM), with a long range objective to better optimize and understand MR fluid behavior in such tribological applications. As in most DEM studies, inter-particle forces are determined by a force-displacement law and trajectories are calculated using Newton’s second law. In this study, particle magnetization and magnetic interactions between particles have been added to the discrete element code. The global behavior of the MR fluid can be analyzed by examining the time evolution of the ensemble of particles. Microscopically, the known behavior is observed: particles align themselves with the external magnetic field. Macroscopically, averaging over a number of particles and a significant time interval, effective viscosity increases significantly when an external magnetic field is applied. These preliminary results would appear to establish that the DEM is a promising method to study MR fluids at the microscopic and macroscopic scales as an aid to tribological design.
Formation of zinc oxide films using submicron zinc particle dispersions
Authors: Rajachidambaram Meena S. , Varga Tamas , Kovarik Libor , Sanghavi Rahul , Shutthanandan Vaithiyalingam , Thevuthasan Suntharampillai , Han Seung-Yeol , Chang Chih-Hung , Herman Gregory S.
Published: June 2012

The thermal oxidation of submicron metallic Zn particles was studied as a method to form nanostructured ZnO films. The particles used for this work were characterized by electron microscopy, x ray diffraction, and thermal analysis to evaluate the Zn-ZnO core shell structure, surface morphology, and oxidation characteristics. Significant nanostructural changes were observed for films annealed to 400 °C or higher, where nanoflakes, nanoribbons, nanoneedles, and nanorods were formed as a result of stress induced fractures arising in the ZnO outer shell due to differential thermal expansion between the metallic Zn core and the ZnO shell. Mass transport occurs through these defects due to the high vapor pressure for metallic Zn at temperatures above 230 °C, whereupon the Zn vapor rapidly oxidizes in air to form the ZnO nanostructures. The Zn particles were also incorporated into zinc indium oxide precursor solutions to form thin film transistor test structures to evaluate the potential of forming nanostructured field effect sensors using simple solution processing.
Combinatorial Small-Molecule Therapy Prevents Uropathogenic Escherichia coli Catheter-Associated Urinary Tract Infections in Mice
Authors: Guiton Pascale S. , Cusumano Corinne K. , Kline Kimberly A. , Dodson Karen W. , Han Zhenfu , Janetka James W. , Henderson Jeffrey P. , Caparon Michael G. , Hultgren Scott J.
Published: June 2012

Catheter-associated urinary tract infections (CAUTIs) constitute the majority of nosocomial urinary tract infections (UTIs) and pose significant clinical challenges. These infections are polymicrobial in nature and are often associated with multidrug-resistant pathogens, including uropathogenic
Escherichia coli
(UPEC). Urinary catheterization elicits major histological and immunological alterations in the bladder that can favor microbial colonization and dissemination in the urinary tract. We report that these biological perturbations impact UPEC pathogenesis and that bacterial reservoirs established during a previous UPEC infection, in which bacteriuria had resolved, can serve as a nidus for subsequent urinary catheter colonization. Mannosides, small molecule inhibitors of the type 1 pilus adhesin, FimH, provided significant protection against UPEC CAUTI by preventing bacterial invasion and shifting the UPEC niche primarily to the extracellular milieu and on the foreign body. By doing so, mannosides potentiated the action of trimethoprim-sulfamethoxazole in the prevention and treatment of CAUTI. In this study, we provide novel insights into UPEC pathogenesis in the context of urinary catheterization, and demonstrate the efficacy of novel therapies that target critical mechanisms for this infection. Thus, we establish a proof-of-principle for the development of mannosides to prevent and eventually treat these infections in the face of rising antibiotic-resistant uropathogens.
Molecular Identification andIn VitroResponse to Antifungal Drugs of Clinical Isolates of Exserohilum
Authors: da Cunha Keith Cássia , Sutton Deanna A. , Gené Josepa , Capilla Javier , Cano Josep , Guarro Josep
Published: June 2012

Exserohilumis an agent of human and animal mycoses. Although classification has been based on a few subtle morphological differences, three species of clinical interest have been traditionally accepted. In this study, by using a multigene sequence analysis, we have demonstrated thatExserohilum longirostratumandE. mcginnisiiare probable synonyms ofE. rostratum. The isolates tested were mainly from the nasal region. Antifungal susceptibility testing demonstrated high activity of the eight agents tested against this fungus.
Effect of Interferon Inducers and Interferon on Bacterial Infections
Authors: Giron David J. , Schmidt Jerome P. , Ball Robert J. , Pindak Frank F.
Published: June 2012

The effect of interferon inducers and exogenous L-cell interferon on the infection of mice by
Pasteurella tularensis
or
Diplococcus pneumoniae
was investigated. The results indicate that the degree of protection is dependent on the type of inducer used. A variety of defense mechanisms with limited nonspecific activity appear to be involved.
Obligate Parasitism of Trachoma Agent: Lack of Trachoma Development in Ethidium Bromide-Treated Cells
Authors: Becker Yechiel , Asher Yael
Published: June 2012

Trachoma agent failed to develop in eukaryotic cells pretreated with ethidium bromide.
Thiopeptin, a New Feed Additive Antibiotic: Microbiological and Chemical Studies
Authors: Miyairi N. , Miyoshi T. , Aoki H. , Kohsaka M. , Ikushima H. , Kunugita K. , Sakai H. , Imanaka H.
Published: June 2012

The thiopeptins are a new group of sulfur-containing peptide antibiotics produced by
Streptomyces tateyamensis
. The antibiotic consists of a major component (designated as thiopeptin B) and four minor ones (thiopeptins A
1
to A
4
). These components were isolated by solvent extraction from mycelium followed by chromatography on silica gel with various ratios of chloroform and methanol as elution solvents. Acid hydrolysis of each of the thiopeptin components yielded 1 mole of valine, 1 of threonine, 1 of cysteine, and 2 of alanine as amino acids. Each component of the thiopeptin A group has chemical and biological properties closely similar to those of thiopeptin B, but detailed characterization has established that thiopeptins A
1
, A
3
, and A
4
are new antibiotics. We could not obtain accurate data for determination of the uniqueness of A
2
because of insufficient sample. Thiopeptin has strong antibacterial activity against gram-positive bacteria and
Mycoplasma
, and exhibits no cross-resistance to major human-use antibiotics.
Bactericidal Action of Streptomycin and Comparison with Spectinomycin in Heterozygotes of
Escherichia coli
Authors: Sparling P. Frederick , Davis Bernard D.
Published: June 2012

Str
s
/
str
r
heterozygotes of
Escherichia coli
K-12 are shown to be sensitive to the lethal as well as the inhibitory action of streptomycin. The rate of killing was lower in heterozygotes than in sensitive homozygotes, and among heterozygotes it was lower in those with a higher proportion of resistant ribosomes. These strains also differed, in a parallel manner, in the kinetics of inhibition of growth and protein synthesis by streptomycin. Similar results were obtained with spectinomycin and corresponding merodiploid strains. Since spectinomycin is purely bacteriostatic and stabilizes polysomes, it must block resistant ribosomes behind inhibited sensitive ribosomes; hence, these results are consistent with an initial similar polysomal blockade by streptomycin. However, since streptomycin causes gradual polysome breakdown, its dominant lethal action must involve some mechanism other than a permanent polysomal blockade.
Effect of Secondary Metabolites on the Organisms Producing Them: Effect of Nisin on
Streptococcus lactis
and Enterotoxin B on
Staphylococcus aureus
Authors: Hurst A. , Kruse H.
Published: June 2012

The effect of secondary metabolites added to cultures of the organisms producing them was investigated. Nisin was added to growing cultures of a nisin-producing strain of
Streptococcus lactis
(354/07) and enterotoxin B to strains of
Staphylococcus aureus
(S6 and 243) producing enterotoxin B. One quarter (12 μg/ml) of the amount of nisin formed by the culture of
S. lactis
inhibited lag-phase cells and lysed log-phase cells. The same amount of nisin added before inoculation or at a time when nisin synthesis had started (in late log phase), caused only transient delay in growth. Inhibition of growth of the two enterotoxin B-producing strains of
S. aureus
could not be demonstrated at any stage of their growth cycle with as much as 1 mg of enterotoxin B per ml of medium.
Cross-Resistance of
Pseudomonas
to Gentamicin and Tobramycin
Authors: Brusch John L. , Barza Michael , Bergeron Michel G. , Weinstein Louis
Published: June 2012

Clinical isolates of gentamicin-resistant organisms were found to be resistant to tobramycin, a new aminoglycoside antibiotic.
Novel Method for Detection of β-Lactamases by Using a Chromogenic Cephalosporin Substrate
Authors: O'Callaghan Cynthia H. , Morris A. , Kirby Susan M. , Shingler A. H.
Published: June 2012

A new cephalosporin with a highly reactive β-lactam ring was found to give an immediate color change in the presence of β-lactamases from many bacteria, including staphylococci,
Bacillus
species,
Enterobacteriaceae
, and
Pseudomonas
. The reaction is confined to organisms producing β-lactamases, but it is sufficiently sensitive to indicate the presence of this enzyme is small amounts in strains previously considered not to produce it. The compound has an unusual ultraviolet spectrum, and the color change can be followed quantitatively by measuring changes in absorption which occur in the 380- to 500-nm region, where cephalosporins normally have no absorption. The development of color is thought to be a consequence of the β-lactam ring being unusually highly conjugated with the 3-substituent. Although in the bacteria only β-lactamases produce this color change, it was found that serum and tissues from experimental animals also rapidly produced the colored breakdown product, which was then excreted in the urine. The mechanism of the mammalian breakdown was considered to be different from that found in bacteria.
Biogenesis of an Antitumor Antibiotic Protein, Neocarzonostatin
Authors: Kudo Kozo , Kikuchi Mikio , Ishida Nakao
Published: June 2012

A study of the biogenesis of the antitumor protein antibiotic neocarzinostatin (NCS) was undertaken. The production of NCS, as well as the growth of
Streptomyces carzinostaticus
in a production medium, was sensitive to puromycin, chloramphenicol, and actinomycin D. However, when a 12-hr culture in production medium was transferred to a nongrowth medium consisting of a phosphate buffer with Mg
2+
and Ca
2+
, rapid NCS synthesis and liberation occurred. NCS production in this medium was no longer sensitive to actinomycin D, but was sensitive to puromycin and chloramphenicol. The conversion of a precursor NCS to an active form was shown to occur in this medium. Subcellular analysis suggested that NCS synthesis occurred by a mechanism similar to that of protein synthesis by membrane polysomes.
Factors Influencing the Microbiological Assay of Tobramycin
Authors: Lamb John W. , Mann Jerry M. , Simmons Richard J.
Published: June 2012

Tobramycin belongs to the aminoglycoside class of antibiotics. Assay procedures were investigated to determine the most suitable methods for the assay of tobramycin in blood, urine, and pharmaceutical preparations. The agar-plate assay was the method of choice for determinations in urine and serum. The turbidimetric assay was selected for the assay of pharmaceutical preparations. An extraction technique is described that minimizes problems encountered in the estimation of tobramycin in urine. Sample diluents,
p
H, and molarity were important and were variable depending on assay methods. Evidence is presented to show binding of tobramycin to α-cellulose susceptibility discs. Iron and sodium ions demonstrated potential inhibition of tobramycin in all assay methods tested.
Analytical Method for Streptothricin-Type Antibiotics: Structure of Antibiotic LL-BL136
Authors: Borders D. B. , Kirby J. P. , Wetzel E. R. , Davies M. C. , Hausmann W. K.
Published: June 2012

An analytical procedure was devised which can distinguish members of the streptothricin family of antibiotics. It is based upon an analysis of the hydrolysis products of the antibiotics using a Technicon amino acid autoanalyzer under special conditions. The various fragments including the different streptolidine-amino sugar compounds were well resolved. A basic water-soluble antibiotic discovered in our laboratories and named LL-BL136 was compared to other members of this group by this technique. It was not differentiated from the antibiotic SF-701 reported by Tsuruoka. The autoanalyzer results along with other physicochemical data permitted a structure proposal for this antibiotic, which is the
N
-methyl-desformimino derivative of antibiotic LL-AC541.
Effect of Several Components of Anaerobic Incubation on Antibiotic Susceptibility Test Results
Authors: Rosenblatt Jon E. , Schoenknecht Fritz
Published: June 2012

The factors influencing the in vitro activity of antibiotics during anaerobic incubation were studied by the disc method with a facultative organism,
Escherichia coli
. We observed the effects of incubation aerobically, anaerobically (Torbal jars), in a CO
2
incubator, and aerobically and anaerobically with all CO
2
removed. We also monitored
p
H changes during incubation and observed the effect of two different initial agar
p
H values (7.4 and 8.3). With aminoglycosides, zones were larger at
p
H 8.3 and, in each agar
p
H group, zones were decreased by incubation with increased CO
2
(anaerobically and CO
2
incubator). A fall in agar
p
H took place during the first 5 to 7 hr of incubation when increased CO
2
was present. Decreased aminoglycoside zones in the presence of increased CO
2
were due to fall in agar
p
H. Erythromycin showed the same zone size changes as the aminoglycosides. Chloramphenicol zones were somewhat smaller at the lower medium
p
H. Zones around tetracycline discs were largest after incubation anaerobically. Further aerobic (or CO
2
) incubation of plates after anaerobic incubation resulted in large “zones of relative inhibition” around the aminoglycoside discs. This suggests that these antibiotics had become more active after exposure to aerobic conditions. Our studies indicate that antibiotic susceptibility test results can be significantly altered by several components of anaerobic incubation including changes in agar
p
H and CO
2
concentration as well as anaerobiosis per se.
Comparison of Clindamycin, Erythromycin, and Methicillin in Streptococcal Infections in Monkeys
Authors: Carlisle Harold N. , Saslaw Samuel
Published: June 2012

Intravenous inoculation of a group A hemolytic streptococcus caused lethal infections in all of eight untreated monkeys. Intramuscular injections of clindamycin-2-phosphate in a daily dose of 25 mg/kg given in equal morning and afternoon doses for 10 days resulted in survival of all of eight monkeys. Similar results were observed with the same dose schedule of clindamycin hydrochloride given intragastrically; no fatalities occurred among eight monkeys. In monkeys receiving erythromycin stearate intragastrically or methicillin intramuscularly, three of eight and four of eight monkeys, respectively, died. Duration of both illness and positive blood cultures was greater in the erythromycin- and methicillin-treated survivors than in the clindamycin-treated monkeys. The differences in results between clindamycin and erythromycin could not be correlated with serum antibacterial activity levels, which were similar, or with minimal inhibitory concentrations, which were 0.02 μg/ml with both antibiotics. With methicillin, however, the minimal inhibitory concentration was 0.16 μg/ml and serum antibacterial activity varied from titers of less than 1:2 to 1:8. As in previous studies of staphylococcal infections in monkeys with the same antibiotics, in vitro susceptibility data and serum antibacterial activity did not completely correlate with in vivo results.
Susceptibility Testing of Anaerobic Bacteria with 100-μg Carbenicillin Disks
Authors: Laslie W. W. , Lambe D. W.
Published: June 2012

A total of 245 strains of anaerobic bacteria were examined for their susceptibility to carbenicillin by the disk test method and by minimum inhibitory concentration (MIC) determinations. Standard-curve studies with a strain of
Bacteroides fragilis
subsp.
fragilis
that was minimally susceptible to carbenicillin and
Escherichia coli
(ATCC 25922) demonstrated that a disk containing 100 μg of carbenicillin was suitable for testing susceptibility of anaerobes to carbenicillin. Thus, the diameter of zones around the 100-μg carbenicillin disks and MIC values were determined under the following test conditions: Mueller-Hinton agar supplemented with sheep blood, vitamin K
1
, and hemin; an incubation temperature of 35 C; and an atmosphere of 80% N
2
, 10% H
2
, and 10% CO
2
. The strains were separated into two populations by correlating zone diameters and geometric mean MICs. The disk test more clearly separated the resistant and susceptible populations and was more reproducible than the MIC test. Thus, a statistical analysis based on the distribution of zone diameters of susceptible and resistant strains was used to derive an interpretive scheme for anaerobic bacteria tested with 100-μg carbenicillin disks. The following interpretive scheme is recommended for testing anaerobes with 100-μg disks of carbenicillin: resistant, 8 mm or less; indeterminate, 9 to 12 mm; and susceptible, 13 mm or greater.
In Vitro Activity of Gentamicin and Minocycline Alone and in Combination Against Bacteria Associated with Intra-Abdominal Sepsis
Authors: Fass Robert J. , Ruiz Daniel E. , Prior Richard B. , Perkins Robert L.
Published: June 2012

The minimal inhibitory concentrations of gentamicin and minocycline alone and in combination were determined by a broth microdilution method for 100 aerobic, facultative, and anaerobic isolates representative of pathogens recovered from patients with intra-abdominal sepsis. Gentamicin inhibited all strains of
Klebsiella, Enterobacter
, and
Pseudomonas aeruginosa
in concentrations of 0.4 to 3.1 μg/ml and all strains of
Escherichia coli
and
Proteus mirabilis
in concentrations of 0.8 to 12.5 μg/ml. Whereas minocycline did not consistently inhibit these organisms in concentrations of 1.6 μg or less/ml, it did act synergistically with gentamicin against 43% of the
Enterobacteriaceae
tested in clinically achievable concentrations; significant synergy was most common with
E. coli
(60%). Minocycline inhibited 62% of
Bacteroides fragilis
, 71% of
Clostridium
, 40% of anaerobic cocci, and 40% of enterococci tested in concentrations of 1.6 μg or less/ml. Whereas gentamicin rarely inhibited these organisms in concentrations of 6.2 μg or less/ml, it did act synergistically with minocycline against 20% of
B. fragilis
, 67% of
Clostridium
, 22% of anaerobic cocci, and 22% of enterococci (which had minimal inhibitory concentrations of minocycline within the range tested) at clinically achievable concentrations. Although only four (13%) of the 30 isolates resistant to both gentamicin and minocycline alone were inhibited by clinically achievable concentrations of the combination, the observed synergy, particularly against strains of
E. coli
, was considered to be of potential clinical usefulness. Antagonism between gentamicin and minocycline was not observed at the concentrations tested.
Characterization and Quantitation of Experimental Surgical-Wound Infections Used to Evaluate Topical Antibacterial Agents
Authors: McRipley R. J. , Whitney R. R.
Published: June 2012

Reproducible experimental surgical-wound infections in mice for use in the evaluation of topical antibacterial agents are described. The experimental would was created on the backs of mice by means of a midline incision and was infected by means of cotton sutures monocontaminated with
Staphylococcus aureus
or
Pseudomonas aeruginosa
. The course of these wound infections was followed by quantitation of surface bacteria through use of a surface rinse technique. Surface wound counts of the infecting organisms thus obtained appeared to reflect the dynamics of the total wound count, as determined by homogenization of biopsied tissue. Treatment of infected wounds with a placebo cream had only a slight effect on surface wound counts and on mortality in the case of the
S. aureus
infection but enhanced markedly the lethality of the
P. aeruginosa
infection.
Responsiveness of Experimental Surgical-Wound Infections to Topical Chemotherapy
Authors: McRipley R. J. , Whitney R. R.
Published: June 2012

Topical agents freshly formulated in a cream base vehicle as well as commercial topical preparations were used to evaluate in mice the responsiveness of experimental surgical wounds infected with
Staphylococcus aureus
or
Pseudomonas aeruginosa
to chemotherapy. The responsiveness of the infections to therapy or the efficacy of a topical agent was assessed primarily by means of wound counts of the infecting organism before and after the employment of an immediate (prophylactic) or delayed (therapeutic) treatment regimen. From tests of several concentrations of an agent formulated in the vehicle, a median effective dose could be determined. In the case of the lethal
P. aeruginosa
infection, a median protective dose could be determined. Both infections were found to be quite susceptible to treatment with those topical agents that demonstrated good activity in vitro against the test organisms. The results of the investigation indicated that the model infections were suitable for the screening of potential topical agents in vivo.
Gentamicin- and Cephalothin-Associated Rises in Blood Urea Nitrogen
Authors: Fanning W. Lee , Gump Dieter , Jick Hershel
Published: June 2012

Standardized rates of drug-attributed rises in blood urea nitrogen were 8.6%, 2.9%, and 9.3%, respectively, in patients receiving gentamicin alone, cephalothin alone, and both drugs together. These results provide evidence against a substantial synergism between the two drugs in the production of impaired renal function.
Inactivation of the Enveloped Bacteriophage ø6 by Butylated Hydroxytoluene and Butylated Hydroxyanisole
Authors: Wanda Paul , Cupp James , Snipes Wallace , Keith Alec , Rucinsky Tom , Polish Louis , Sands Jeffrey
Published: June 2012

Butylated hydroxytoluene (BHT) is a potent inactivator of the enveloped bacterial virus ø6 at concentrations as low as 3 × 10
−5
M. The viral envelope is not removed by BHT treatment, in contrast to the effects of exposure to the detergent Triton X-100. BHT-treated viruses are morphologically indistinguishable from controls but are defective in their ability to attach to the host cell. Temperature at the time of exposure was found to be a crucial factor in the effectiveness of BHT against ø6. A precipitous drop in the degree of inactivation by 3 × 10
−5
M BHT occurred when the temperature was lowered from 20 to 15 C. Calcium ions were found to potentiate the effect of BHT, particularly at lower temperatures where BHT alone was relatively ineffective. Barium and strontium, but not magnesium, were also effective in enhancing the activity of BHT. A structurally related molecule, butylated hydroxyanisole (BHA), was also found to inactivate ø6 virus, but higher concentrations were required than with BHT. Both BHT and BHA are commonly used as food additives, have apparent low toxicity to humans and other animals, and are potentially useful as antiviral agents.
Photoinactivation of Latent Herpes Simplex Virus in Rabbit Kidney Cells
Authors: Kelleher J. J. , Varani J.
Published: June 2012

The photoinactivation of actively and nonactively growing herpes simplex virus by neutral red and proflavine was studied in rabbit kidney cells. Active virus growth was inhibited by both dyes under conditions which did not destroy the cells. Neutral red caused a much greater inhibition than proflavine. Neutral red also caused a reduction in the reactivation rate of latent virus when the infected cells were treated during the latent period. In the treated cultures that did reactivate virus, the average length of the latent period was increased over the control value. Proflavine treatment did not reduce the rate of reactivation of latent virus and did not increase the average latent period of the treated cultures.
In Vitro Susceptibility of Common Clinical Anaerobic and Aerobic Isolates Against Josamycin
Authors: Reese Richard E. , Betts Robert F. , Goedde Lola W. , Douglas R. Gordon
Published: June 2012

The in vitro susceptibility of 145 anaerobic clinical isolates and 96 gram-positive aerobic clinical isolates to josamycin, a new macrolide antibiotic, was studied using the agar dilution technique. Ninety-five of the aerobes were susceptible to 1.56 μg or less of josamycin per ml. The median minimal inhibitory concentration of these organisms was ≤0.39 μg/ml. The in vitro activity of josamycin against the anaerobes was compared with that of erythromycin, clindamycin, penicillin, and chloramphenicol. At concentrations ≤3.12 μg/ml, 100% of strains of
Bacteroides
species and
Bacteroides fragilis
were susceptible to josamycin. At low concentrations (≤0.39 μg/ml), clindamycin was more active than josamycin against the anaerobes. However, at concentrations ≤3.12 μg/ml, the activities of josamycin and clindamycin were similar except against the
Fusobacterium
species, which was quite resistant to josamycin.
Effect of Gentamicin on Growth of Viral, Chlamydial, and Rickettsial Agents in Mice and Embryonated Eggs
Authors: White Lendell A. , Hall Henrietta E. , Tzianabos T. , Chappell W. Adrian
Published: June 2012

Gentamicin, at concentrations up to 500 μg/ml, showed no effect on the replication, yield, or infectivity of seven viruses or on the agents of psittacosis and meningopneumonitis when grown in mice or embryonated eggs. At the 500 μg/ml level, lymphogranuloma venereum cultures had a slight reduction in infectivity.
Rickettsia akari
demonstrated susceptibility at the 5 μg/ml level, whereas
R. rickettsii, R. mooseri
, and
R. canada
grown in embryonated eggs were susceptible in varying degrees to gentamicin at or above the 50 μg/ml concentration.
Concentrations of Trimethoprim-Sulfamethoxazole in Blood After a Single, Large Oral Dose
Authors: Yoshikawa Thomas T. , Guze Lucien B.
Published: June 2012

Concentrations of trimethoprim (TMP) and sulfamethoxazole (SMZ) in blood were determined in seven healthy volunteers after ingestion of 720 mg of TMP and 3,600 mg of SMZ (nine tablets of TMP-SMZ, 1:5 ratio) as a single oral dose. The mean levels of drug in blood achieved during the first 8 h after drug administration ranged from 6.12 to 8.32 μg/ml for TMP and 98 to 120 μg/ml for SMZ. These concentrations easily exceeded the previously reported minimal inhibitory concentrations for clinical isolates of
Neisseria gonorrhoeae
. The combination of TMP-SMZ given as a single, large oral dose may be a useful therapeutic regimen for patients with uncomplicated gonorrhea and susceptible microorganisms.
Pirbenicillin: Pharmacokinetic Parameters in Mice
Authors: English Arthur R. , Girard Dennis , Retsema James A.
Published: June 2012

The rapid intravenous administration to mice of pirbenicillin, carbenicillin, and ampicillin produced biexponential blood concentration-time curves when assessed by frequent blood samplings at short intervals. The pharmacokinetic behavior of pirbenicillin and the other penicillins was analyzed by the two-compartment open model. This is thought to be the first study giving detailed pharmacokinetic values of penicillins in mice. Some significant differences were noted between the pharmacokinetic values of pirbenicillin, ampicillin, and carbenicillin. These values suggest that the interchange of pirbenicillin between the central and peripheral body compartments of the mouse was slower than that of either carbenicillin or ampicillin and indicated that a greater fraction of the pirbenicillin than the ampicillin dose reached the peripheral compartment.
New Method for Detecting In Vitro Inactivation of Penicillins by
Haemophilus influenzae
and
Staphylococcus aureus
Authors: Lee Wie-Shing , Komarmy Louis
Published: June 2012

A new technique for detecting penicillinase production in
Haemophilus influenzae
and
Staphylococcus aureus
was compared with the capillary procedure for detecting beta-lactamase and the Bauer-Kirby disk susceptibility procedure. Isolates were classified similarly by all three procedures.
Antiviral Effects of Virazole in Chronic Hepatitis B Surface Antigen-Seropositive Chimpanzees
Authors: Denes Alexander E. , Ebert James W. , Berquist Kenneth R. , Murphy Bert L. , Maynard James E.
Published: June 2012

Virazole (Ribavirin, ICN 1229), a broad-spectrum, antiviral chemotherapeutic agent was used to treat two adult chronically hepatitis B surface antigen (HB
s
Ag)-seropositive chimpanzees. No significant change in serum hepatitis B surface antigen was noted and no adverse reactions were observed. The role of viral replication in the chronic carrier state of hepatitis B is discussed.