Immunohistochemical differential diagnosis of pleural effusions, with emphasis on malignant mesothelioma.
The immunohistochemical diagnosis of atypical epithelial proliferations in pleural fluid is a challenging topic in cytopathology and surgical pathology. Mesothelioma may be simulated clinically and radiologically by several other nonneoplastic and neoplastic disorders, mandating that strict histologic, histochemical, immunohistochemical, and ultrastructural guidelines be followed for its diagnosis. Because of its availability to most laboratories, immunohistochemistry has emerged as the most commonly used procedure for the diagnosis of pleural malignancies. This review considers the current status of that investigative modality, with particular attention to lesions that are suspected to be mesothelial.


Mitral cell-to-glomerulus connectivity: an HRP study of the orientation of mitral cell apical dendrites.
It has been suggested that the principal output cells of the main olfactory bulb, the mitral cells, along with the glomerulus they enter, form an anatomical and functional column. To test the extent to which mitral cell somata lying close together in the mitral cell layer are connected to the same glomerulus, we reconstructed 267 mitral cells labeled by extracellular injections of horseradish peroxidase (HRP) in the external plexiform layer. Results show that apical dendrites tilt rostrally from the somata to the glomeruli and this tilt is gradually greater as the somata are located more and more rostrally in the olfactory bulb. The apical dendrites of most mitral cells in the same region of the bulb are parallel. We analyzed the degree to which dendrites were parallel by measuring the difference in angle of all pairs of apical dendrites in each section, with the restriction that no cells were separated by more than 500 microns. About half of these pairs of dendrites differed in angle by 20 degrees or less and were therefore said to be parallel. The degree of parallelism did not vary with the cell pair location or with intercell distance. Study of glomerular connections of pairs of mitral cells as a function of intercell distance revealed that 96% of mitral cells connected to the same glomerulus were separated by less than 120 microns, while 72% of cells connected to adjacent glomeruli and only 29% of cells connected to distant, i.e., nonadjacent, glomeruli were separated by less than 120 microns.(ABSTRACT TRUNCATED AT 250 WORDS)


Changing relations between hospitals and primary health care: new challenges for hospital management.
Hospitals in the Netherlands are now operating in a rapidly changing environment. Most changes directly result from government's policy to achieve effective cost containment in health care. Some of them basically affect the existence and functioning of hospitals. These changing environmental conditions inspire hospitals to undertake innovative activities to protect or even strengthen their position. This will be illustrated below by a case in which a small acute hospital attempted to establish a close relationship with primary health care in order to protect its position. Our focus will be upon this innovative initiative and upon some management problems that must then be resolved.


Validation of an equation for calculation of glucose appearance during nonsteady state in sheep.
The purpose of this study was to validate the calculation of the rate of glucose appearance (RA) during nonsteady state for sheep. The RA given by the modified single-compartment model was compared with the actual rate derived from the sum of the infusion of exogenous glucose and endogenous production as determined from hepatic production of glucose. Using a pool fraction of 0.65, the error associated with calculation of RA was about 10%.


Outcome of pediatric patients treated with extracorporeal life support after cardiac surgery.
Extracorporeal life support (ECLS) has been used for over two decades in select patients after cardiac surgery. We previously described factors associated with death in this population. We now review our recent experience to reassess factors related to mortality. All pediatric patients who received ECLS support within 7 days after surgery between July 1995 and June 2001 were examined to describe clinical features associated with survival. We compared the results with our prior report to assess changes in practice and outcome. Seventy-four patients were followed. Fifty percent survived to discharge. Hospital survival was not significantly related to patient age, cannulation site, or indication. Thirty-five percent of patients required hemofiltration while on ECLS and were significantly less likely to survive (23% vs 65%). A multivariate analysis combining all children from our prior report with the present cohort revealed that patients who received hemofiltration were five times more likely to die (odds ratio 5.01, 95% confidence interval 2.11-11.88). Children with an adequate two-ventricular repair had lower risk of death (odds ratio 0.42, 95% confidence interval 0.19-0.91) after adjusting for patient age, study period, and hours elapsed before initiation of ECLS after surgery. Patients with an adequate two-ventricle repair have significantly higher hospital survival, whereas those with single ventricle physiology or need for dialysis have decreased survival.


Effects of HER2-binding affibody molecules on intracellular signaling pathways.
HER2, which is overexpressed in 25-30% of human breast cancers, is a tyrosine kinase receptor critical for the signal transduction network that regulates proliferation, migration and apoptosis of cells. We report the effects of two novel HER2-binding affibody molecules (Affibody), (ZHER2:4)2 and ZHER2:342, on intracellular signal transduction pathways (Erk1/2, Akt and PLCgamma1) using quantitative immunoblotting techniques and their biological effects in cell culture. The clinically approved antibody trastuzumab (Herceptin) was used as reference substance. Our data showed that, although all substances target HER2, the effects on the receptor and signaling molecules differed. For example, HER2 phosphorylation was induced by trastuzumab and (ZHER2:4)2 but inhibited by ZHER2:342. The effects these substances had on signal transduction correlated to some degree with changes in growth and migration, e.g. (ZHER2:4)2 stimulated phosphorylation of Erk1/2 and PLCgamma1, as well as growth and migration, while ZHER2:342 did not. ZHER2:342 even inhibited phosphorylation of PLCgamma1 and migration. Our data suggest that ZHER2:342 is a promising small agent (7 kDa) that may be used as an alternative, or complement, to trastuzumab. If radiolabelled, it can hopefully also be used for HER2 imaging and radionuclide therapy.


Adenosine A(2A) receptor antagonists KF17837 and KW-6002 potentiate rotation induced by dopaminergic drugs in hemi-Parkinsonian rats.
The effects of novel adenosine A(2A) receptor antagonists KF17837 ((E)-1,3-dipropyl-8-(3,4-dimethoxystyryl)-7-methyl-3, 7-dihydro-1H-purine-2,6-dione) and KW-6002 ((E)-1,3-diethyl-8-(3, 4-dimethoxystyryl)-7-methyl-3,7-dihydro-1H-purine-2,6-dione), on rotational behavior induced by apomorphine or L-DOPA (L-3, 4-dihydroxyphenylalanine) were investigated in rats with unilateral 6-hydroxydopamine lesions. Both KF17837 and KW-6002 slightly induced rotational behavior per se. However, KF17837 and KW-6002 significantly increased the total counts of turning induced by apomorphine at doses of 3 mg/kg, p.o. and 10 mg/kg, p.o., and at doses of 1 mg/kg, p.o. and higher, respectively. KF17837 and KW-6002 also potentiated the rotational behavior induced by L-DOPA at a dose of 3 mg/kg, p.o. Furthermore, i.c.v. injection (10 microg/20 microl) of a selective adenosine A(2) receptor agonist CGS 21680 [2-[p-(2-carboxyethyl)phenethylamino]-5'-N-ethylcarboxamidoaden osine] partially prevented the rotational behavior induced by apomorphine and this inhibition was reversed by KW-6002 (1 mg/kg, p.o.). The increase in total counts of apomorphine-induced turning by the adenosine A(2A) receptor antagonists seems to be mainly attributable to prolongation of turning duration rather than enhancement of intensity. These results suggest that these adenosine A(2A) receptor antagonists may be useful to ameliorate shortening in the duration of dopaminergic drug response in patients with advanced Parkinson's disease.


Approaches to analysis of dietary data: relationship between planned analyses and choice of methodology.
Dietary intake cannot be estimated without error and probably never will be. The nature and magnitude of the error depends on both the dietary data collection methodology and the subjects studied. The impact of particular types of error depends on the question being asked and the analytical methodology used to address it. Examples of these phenomena are presented in this review paper. The future lies in improved estimation and understanding of the error terms and in the development of analytical and statistical methods of coping with these error terms rather than with "improvements" in dietary methodology per se.


Molecular characterization of the hdm2-p53 interaction.
A number of viral oncogenes target the tumour suppressor protein p53 and inactivate its function. This is an important step in tumourogenesis. The cellular oncogene hdm2 acts through a similar mechanism. It binds the N terminus of p53, thereby interfering with the ability of p53 transcriptionally to activate genes responsible for growth arrest or apoptosis after genotoxic insults. The disruption of the interaction of the two proteins therefore comprises a promising therapeutic target for treatment of the subset of human cancers in which this pathway is active. In this paper we attempt to characterize the p53-hdm2 interaction biochemically. We analyse the potential of a series of peptide inhibitors, derived from previously described mdm2 binding peptide display phage, to disrupt this interaction in ELISA assays. We conclude that F19, W23 and L26 of p53 are critical contact points for p53 binding to hdm2. Furthermore, we show the potential of the monoclonal antibody 3G5 to interfere with binding of p53 to hdm2 in ELISA assays. Consequently, we define the binding site of 3G5 on hdm2 using overlapping peptides derived from the N terminus of hdm2 and phage display libraries. The result indicates L66, Y67 and E69 on hdm2 as critical binding points for 3G5. In electrophoretic mobility shift assay we demonstrate the formation of hdm2-p53 complexes that can be disrupted in the presence of 3G5 or inhibitory peptides. Finally, we describe the effects of NEM and DTT on the interaction between the two molecules in ELISA assays. All our results are discussed in the light of the recently published crystal structure of the mdm2-p53 complex. A striking correspondence between our findings and the crystal structure is revealed.


Theoretical investigations on the mechanistic pathway of the thermal rearrangement of substituted N-acyl-2,2-dimethylaziridines.
The mechanism of the thermal rearrangement of substituted N-acyl-2,2-dimethylaziridines 1 has been studied using quantum chemistry methods. Geometries of reactants, transition states and products have been optimized at the B3LYP/6-311++G(2d,2p) level. Relative energies for various stationary points have been determined and reaction identified by IRC calculations. The results show that thermal rearrangements occur in three ways. Firstly, the transition state TS 1 in which a hydrogen atom of methyl groups migrates from primary carbon to oxygen of amid group to give the N-methallylamide 2. The second is via the transition state TS 2 in which the attack of oxygen to the tertiary carbon yields the oxazoline 3. The third is via the transition state TS 3 in which a hydrogen migrate from the secondary carbon to oxygen to give the vinylamide 4. In order to get insights into the factors determining the exact nature of its interactions with electrophiles, the application of reactivity parameters derived from density functional theory in a local sense, in particular the softness and Fukui function, to interpret and predict the mechanisms of the thermal decomposition of the N-acyl-2,2-dimethylaziridines 1, has been discussed.


Trypanocidal Trixikingolides From Trixis Vauthieri.
Chagas disease is an illness caused by the protozoan parasite Trypanosoma cruzi. Only two drugs are available, with the drawback of low rate of cure in the chronic phase of the disease and undesirable side effects. These facts highlight the need to find new compounds for Chagas disease chemotherapy. We describe the isolation and identification of an inseparable mixture of two new trixikingolides from Trixis vauthieri, a plant from family Asteraceae, which present outstanding in vitro trypanocidal activity, with IC50 value of 0.053 µM against the intracellular trypomastigotes and amastigotes forms of T. cruzi infecting L929 cells. The IC50 of the mixture against the host cells is 68 times higher and about 70 times more potent than benznidazole, the reference drug used as control at the experiments. The next step, which depends on obtaining larger quantities of the mixture, is to test it on mice infected with T. cruzi.


Evaluation of six enzyme immunoassays for antibody against human immunodeficiency virus.
Six commercial enzyme immunoassays (EIA) were evaluated in 6488 serum samples, with immunoblot analysis as the confirmatory test for antibodies against human immunodeficiency virus (HIV). The Abbott and Wellcome tests identified all 163 immunoblot-positive samples correctly, whereas the other tests did not detect 1-3 samples. In AIDS patients (predominantly with antibodies to gp41env) Organon's EIA was less sensitive (p less than 0.05) and Wellcome's more sensitive (p less than 0.05) than the immunoblot assay. In symptom-free anti-HIV-positive subjects (antibodies to almost all viral antigens and high titres of anti-p24gag) all the EIA were significantly (p less than 0.05) less sensitive than the immunoblot assay. The frequencies of false-positive reactions in a "tricky" panel of samples from patients with autoimmune and acute viral diseases and in a blood-donor panel were Abbott 9.5%, 0.42%: Organon 1.7%, 0%; Litton 1.0%, 0.4%; Behring 2.7%, 0.06%; Wellcome 0%, 0%; and Pasteur 0%, 0.02%. The results of a seventh EIA (Dupont) were excluded from the study at the company's request. All six EIA evaluated are suitable tests for anti-HIV screening in samples from patients and blood donors.


Nonthyroidal illnesses syndrome in full-term newborns with sepsis.
To assess hormonal changes in nonthyroidal illness syndrome (NTIS) in full-term newborns (NT) with sepsis. We included 28 NT with sepsis divided into 2 groups according to the time of normalization of serum and clinical indicators of infection: group A(A), 16 NT with improvement in up to 8 days; and group B(B), 12 NT improvement after 8 days. Among the 28 NT, 15 NT progressed to septic shock, with 5 NT group A and 10 NT in group B. NT were excluded when they showed severe sepsis and asphyxia, and congenital malformations, as well as those whose mothers had thyroid disease and IUGR. 17 NT (60.7%) presented NTIS. Low T3 was observed in NTIS in 10 NT (58.8%), and low T4 and T3 in 5 NT (29.5%), all of them with septic shock. Two NT showed mixed changes (11.7%). After sepsis was cured, there was no hormonal change, except in 3 NT. Administration of dopamine, furosemide, and corticosteroids did not affect the results. This study indicates that nonthyroidal illness syndrome may be transiently present during sepsis in full-term newborns, especially in cases of prolonged sepsis. Low T3 can occur without changes in reverse T3 (different from adults), and low T4 and T3 occur mainly in patients with septic shock.


Peritoneal fluid cytokines and the relationship with endometriosis and pain.
It is generally accepted that the current scoring system for endometriosis has little correlation with clinical symptoms such as pain, and therefore we may deduce that either endometriosis does not cause pain, or that the current scoring system does not indicate the biological activity of the disease. Pain may occur because the presence of endometriosis produces an intraperitoneal inflammatory response, and several studies have shown that the cytokine content of peritoneal fluid differs between women with and without endometriosis. We studied the relationship between tumour necrosis factor alpha (TNF alpha), platelet-derived growth factor (PDGF), interleukin (IL)-6, IL-4 and TNF (alpha and beta) activity in peritoneal fluid and the clinical history of pain and infertility. TNF alpha concentrations were increased in peritoneal fluid of women with endometriosis and of infertile women; PDGF concentrations were increased in peritoneal fluid of parous women; IL-6 was increased in peritoneal fluid of women with adhesions; IL-4 was absent from peritoneal fluid. PDGF and IL-6 concentrations were cycle related, with the highest amounts in the menstrual and proliferative phases respectively. We failed to demonstrate any association between concentrations of cytokines in vitro and pain symptoms or severity of endometriosis.


A test for predicting propensity of activated sludge to acute filamentous bulking.
Filamentous bulking is a solid-liquid separation problem well known to activated-sludge plant operators. The use of curative additives is a rather delicate solution and the tools developed to anticipate it seem limited. To complement existing sludge sedimentation monitoring tools, a new test to assess the propensity of activated sludge for filamentous bulking was developed. It consists of challenging the sludges by feeding them under conditions favoring filamentous bacteria for 24 hours. The effects of such an acute treatment on sludge settleability is subsequently assessed through a simple sludge volume (SV30) measurement with reference to a control. The sludge can then be evaluated as prone to bulking (unstable sludge) or not (stable sludge). Such a test can be used to predict the occurrence of filamentous bulking in activated-sludge treatment plants. This so-called acute bulking test requires simple equipment and can be done by any wastewater treatment plant operator.


[Genetic causes of obesity].
Overweight and obesity represent an increasing health problem. Both genetic and environmental factors contribute to the development of obesity. This article summarises the genetic aspects of these conditions. A literature search was conducted using PubMed and OMIM. Both original and review articles were included. The genetic influence on body weight is shown by twin and family studies. Environmental changes in recent decades have promoted the development of obesity in individuals at risk because of their genetic composition. Our understanding of the molecular pathways underlying common obesity is limited. During the last decade a handful of monogenic disorders leading to early, severe obesity in humans have been identified. All affect the central regulation of appetite. These conditions are rare, except for mutations in the melanocortin 4 receptor that account for about 5% of morbidly obese patients (BMI > 40 kg/m). The identification of monogenic forms of obesity has contributed valuable insight into the regulation of appetite and development of obesity, although causal treatment only exists for leptin deficiency. In addition, several well defined Mendelian syndromes are associated with overweight and obesity. The molecular genetic cause is known for some of these syndromes, but how appetite and energy balance are affected is still unclear.


Safety of high-dose recombinant erythropoietin in a neonatal rat model.
High-dose recombinant erythropoietin (rEpo) is neuroprotective in neonatal animal models of brain injury, but the long-term consequences of neonatal exposure have not been studied. We hypothesized that multiple injections of high-dose rEpo during the neonatal period would be safe, and would improve neurologic outcomes after exposure to neonatal hypoxia or hypoxic-ischemic injury. Three experimental groups of Sprague-Dawley rats were assessed: (1) normoxia, (2) hypoxia and (3) hypoxia-ischemia. Groups 1 and 2 were given 0, 2,500 or 5,000 U/kg rEpo subcutaneously for the first 5 days of life (P1-P5). Group 2 animals also underwent 2 h of hypoxia (8% O(2)) daily from P1-P3. Group 3 animals underwent right carotid artery ligation followed by hypoxia (8% O(2) x 90 min) on P7, followed by either vehicle or rEpo (2,500 U/kg subcutaneously QD x3). We evaluated short- and long-term physiologic and behavioral outcomes. Major organs were evaluated grossly and histologically. rEpo treatment transiently raised hematocrit, prevented hypoxia-induced delays in geotaxis and growth, improved forelimb strength, promoted liver growth in males, lowered the adult platelet count, but did not alter other CBC indices or histology. rEpo prevented hypoxia-ischemia-induced learning impairment and substantia nigra neuron loss. Repeated treatment of newborn rats with high-dose rEpo was safe under all conditions tested. rEpo treatment improved the development of hypoxia-exposed newborns and prevented the learning impairment and dopamine neuron loss due to unilateral hypoxic-ischemic brain injury.


Protein kinase C-beta inhibitor enzastaurin (LY317615.HCI) enhances radiation control of murine breast cancer in an orthotopic model of bone metastasis.
Radiation therapy is a widely used treatment for metastatic bone cancer, but the rapid onset of tumor radioresistance is a major problem. We investigated the radiosensitizing effect of enzastaurin, a protein kinase Cbeta (PKCbeta) inhibitor, on bone tumor growth and tumor-related pain. We found that enzastaurin enhanced the effect of ionizing radiation on cultured murine 4T1 breast cancer and murine endothelial cells, suppressing their proliferation and colony formation. Enzastaurin and ionizing radiation also induced caspase-mediated apoptosis of 4T1 cells to a greater degree than radiation alone. Enzastaurin treatment of 4T1 cells blocked the phosphorylation of PKCbeta, as well as Ras and two of its downstream effectors ERK1/2 and RAL-GTP. Using an orthotopic model of bone metastasis, we observed that a combination of enzastaurin and localized radiation treatment reduced tumor blood vessel density, bone destruction and pain compared to single modality treatment. In conclusion, we demonstrate that inhibition of PKCbeta in combination with localized radiation treatment suppresses tumor growth and alleviates pain as compared to radiation-only treatment. We also show that the radiosensitizing effect of enzastaurin is associated with suppression of tumor cell proliferation and tumor-induced angiogenesis possibly through inhibition of the Ras pathway.


Evolution and elements of the quality oncology practice initiative measure set.
Over the past 5 years, the American Society of Clinical Oncology (ASCO) has supported the development of a Web-based quality-reporting tool in response to a recognized need to provide medical oncologists the opportunity to demonstrate the quality of care that they are providing to patients. The development of quality measures, their basis in the literature, and the descriptions and organizational structure of the measures are discussed. Specific results are the property of practices and are not shared outside of the practices except in aggregate. The system allows collection of information concerning a wide range of quality measures in a short period of time. In the last data collection period in the fall of 2008, information was submitted concerning 81 measures of quality divided into one required and six optional modules from over 250 practices concerning 15,000 patients. The timely collection of information on a wide range of quality measures regarding cancer patients can be efficiently collected using a Web-based data collection tool allowing for practice self-examination and comparison with other practices.


Discovery and structure-activity relationships of small molecules that block the human immunoglobulin G-human neonatal Fc receptor (hIgG-hFcRn) protein-protein interaction.
The neonatal Fc receptor, FcRn, prolongs the half-life of IgG in the serum and represents a potential therapeutic target for the treatment of autoimmune disease. Small molecules that block the protein-protein interactions of human IgG-human FcRn may lower pathogenic autoantibodies and provide effective treatment. A novel class of quinoxalines has been discovered as antagonists of the IgG:FcRn protein-protein interaction through optimization of a hit derived from a virtual ligand-based screen.


[Urogenital tuberculosis : current status and future perspectives (author's transl)].
Results of a retrospective study of 72 patients with urogenital tuberculosis admitted to Hôpital Cochin Paris, from 1970 to 1980, were compared with those of studies conducted since 1945. Though there has been a marked reduction in the number of cases of tuberculosis in absolute terms, morbidity has not altered as a nephrectomy was performed in 44 p. cent of cases both in the period 1970 to 1980, and the year 1950. There has, however, been a noticeable increase in the use of plastic surgery. Future perspectives involve both the medical and surgical fields, in the former leading to a shorter period (9 months) of treatment, and in the latter by the development of new endoscopic procedures: modelling ureteral sounds, and hydrostatic bladder distention. It is reasonable to assume that surgery will be required less often in the future, medical treatment involving endoscopic procedures being sufficient to treat the majority of urogenital tuberculosis cases.


Response of host plants to periodical cicada oviposition damage.
Insect oviposition on plants is widespread across many systems, but studies on the response of host plants to oviposition damage are lacking. Although patterns of oviposition vary spatially and temporally, ovipositing insects that exhibit outbreak characteristics may have strong effects on host plants during peak abundance. Periodical cicadas (Magicicada spp.), in particular, may reduce the performance of host plants when they synchronously emerge in massive numbers to mate and oviposit on host plants. Here we provide the first experimental manipulation of host plant use by periodical cicadas to evaluate the impact of cicada oviposition on plant performance across a diversity of host species within an ecologically relevant setting. Using a randomized block design, we established a plantation of three native and three exotic host plant species common to the successional forests in which cicadas occur. During the emergence of Brood X in 2004, we employed a highly effective cicada exclusion treatment by netting half of the host plants within each block. We assessed multiple measures of host plant performance, including overall plant growth and the growth and reproduction of individual branches, across three growing seasons. Despite our thorough assessment of potential host plant responses to oviposition damage, cicada oviposition did not generally inhibit host plant performance. Oviposition densities on unnetted host plants were comparable to levels documented in other studies, reinforcing the ecological relevance of our results, which indicate that cicada oviposition damage did not generally reduce the performance of native or exotic host plants.


Cochlear implantation with round window insertion in children with otitis media with effusion.
To discuss indications and surgical techniques for cochlear implantation (CI) in children with profound sensorineural hearing loss and otitis media with effusion (OME). Between January 2003 and May 2013, a total of 550 patients received cochlear implants at the Anhui Provincial Hospital, Hefei, China. Of these, 30 children with OME underwent CI with round window insertion in one stage. One-stage operations of CI with round window insertion were carried out in 30 children with OME. All electrodes were implanted successfully. CI was performed without complications and the electrode arrays were protected well. All implant devices worked normally and all patients performed well during an average follow-up period of 12 months. None of the patients experienced any immediate or delayed postoperative infection-related complications. CI with round window insertion could be safely and effectively performed in one stage in children with profound sensorineural hearing loss and OME. It is unnecessary to delay implantation to control OME, but it remains a challenging problem in operation.


[Synchronous fluorimetric determination of the residues of three quinolones in Eel by partial least squares].
In the present paper, the synchronous fluorimetric spectra of norfloxacin, lomefloxacin chlorhydric acid, and levofloxacin lactate with deltalambda = 190 nm in a B-R buffer medium of pH 2.87 were measured, and the partial least squares (PLS) method was applied to the quantitative resolution of the seriously overlapped fluorimetric spectra of these compounds. The linear ranges for norfloxacin, lomefloxacin chlorhydric acid, and levofloxacin lactate are 0.016-0.40 microg x mL(-1), 0.01-0.336 microg x mL(-1) and 0.01-0.336 microg x mL(-1), respectively. The limits of detection are 0.012 6 microg x mL(-1) for norfloxacin, 0.006 microg x mL(-1) for lomefloxacin chlorhydric acid, and 0.007 2 microg x mL(-1) for levofloxacin lactate. The analytical results by PLS were compared with principal components regression (PCR) and classical least squares (CLS), and this method was applied to the determination of these three compounds in eel samples with satisfactory results.


Opening wedge tibial osteotomy: the 3-triangle method to correct axial alignment and tibial slope.
Although a change in tibial slope may occur during a medial opening wedge osteotomy, calculations have not been defined to address this problem. The authors investigated geometric factors important to correct axial alignment and tibial slope during osteotomy. To calculate, through 3-dimensional analysis of the proximal tibia, how the angle of the opening wedge along the anteromedial tibial cortex influences the tibial slope (sagittal plane) and valgus correction (coronal plane) during osteotomy, and to analyze the different radiographic methods reported in the literature to measure medial and lateral tibial slope. The authors postulated that differences in reported normal values of tibial slope in the sagittal plane were technique dependent. Descriptive laboratory study. The proximal anteromedial tibial cortex obliquity on magnetic resonance imaging was measured in 35 knees. Serial computed tomography images of the proximal tibia were digitized, allowing a series of virtual opening wedge osteotomies to be performed. Algebraic calculations defined the effect of an opening wedge osteotomy on the anteromedial tibial cortex opening wedge angle, sagittal tibial slope angle, and coronal valgus alignment. The anteromedial tibial cortex oblique angle at the medial osteotomy site was 45 degrees +/- 6 degrees and determined, along with the degrees of valgus correction, the degrees of the opening wedge angle in the oblique plane. The anterior osteotomy gap at the tibial tubercle was generally one half of the posteromedial gap to maintain the normal sagittal tibial slope. Every millimeter of gap error at the tibial tubercle resulted in approximately 2 degrees of change in the tibial slope. The width of the buttress plate along the anteromedial tibial cortex was 2 to 3 mm less than the computed coronal valgus posteromedial osteotomy gap to achieve tibiofemoral valgus correction. A series of measurements preoperatively and intraoperatively are required to obtain the desired correction of tibial slope and valgus alignment.


Multiple patch-test reactions: a pilot evaluation of a combination approach to visualize patterns of multiple sensitivity in patch-test databases and a proposal for a multiple sensitivity index.
The variety of patterns of multiple sensitivity in patch-test data remains poorly defined. Studies addressing this topic have primarily concerned the occurrence of pairs of allergens, and some reports hypothesize a predisposing factor that influences the individual sensitivity of patients to multiple reactions. The aim of this study was to address this topic by reanalyzing a matched data set from two patch-test units in Cleveland, OH, and one unit in Cologne, Germany, focusing on multiple reactions to identical allergens of the standard screening trays over the same 4-year period. Based on the statistical FREQ procedure (SAS Institute Inc., Cary, NC), we propose a program for addressing the difficulties in computing and visualizing patterns of multiple sensitivity. Additionally, we propose the "multiple sensitivity index" (MSI) as an absolute measure for characterizing the occurrence of an allergen with others on a selected panel. For the seventeen allergens examined, 131072 possible combinations were evaluated in a total of 2881 patients. Of patients tested, 12.4% had multiple positive patch-test reactions to two to seven allergens. However, because of the small number of patients with the crucial number of possible combinations, no cluster patterns were evident in the three- to seven-allergen combinations. Pairs of allergens most frequently observed were nickel sulfate and potassium dichromate (n = 23), formaldehyde and quaternium-15 (n = 18), and nickel sulfate and formaldehyde (n = 13). We found that nickel sulfate, once again the most frequent sensitizer, occurred in the majority of noncombined cases (MSI = -0.280). Larger patch-test databases require evaluation to obtain further evidence of cluster patterns of multiple sensitivity and to validate the MSI.


Bioeffects caused by changes in acoustic cavitation bubble density and cell concentration: a unified explanation based on cell-to-bubble ratio and blast radius.
Acoustic cavitation has been shown to load drugs, proteins and DNA into viable cells as a complex function of acoustic and nonacoustic parameters. To better understand and quantify this functionality, DU145 prostate cancer cell suspensions at different cell concentrations (2.5 x 10(5) to 4.0 x 10(7) cells/mL) were exposed to 500 kHz ultrasound (US) over a range of acoustic energy exposures (2 to 817 J/cm(2); peak negative pressures of 0.64 to 2.96 MPa; exposure times of 120 to 2000 ms) in the presence of different initial concentrations of Optison contrast agent bubbles (3.6 x 10(4) to 9.3 x 10(7) bubbles/mL). As determined by flow cytometry, molecular uptake of calcein and cell viability both increased with increasing cell density; viability decreased and uptake was unaffected by increasing initial contrast agent concentration. When normalized relative to the initial contrast agent concentration (e.g., cells killed per bubble), bioeffects increased with increasing cell density and decreased with increasing bubble concentration. These varying effects of contrast agent concentration and cell density were unified through an overall correlation with cell-to-bubble ratio. Additional analysis led to estimation of "blast radii" over which bubbles killed or permeabilized cells; these radii were as much as 3 to 90 times the bubble radius. Combined, these results suggest that extensive molecular uptake into cells at high viability occurs for low-energy exposure US applied at a high cell-to-bubble ratio.


Gene isolation in Arabidopsis thaliana by conditional overexpression of cDNAs toxic to Saccharomyces cerevisiae: identification of a novel early response zinc-finger gene.
In an effort to identify novel regulatory plant genes, conditional overexpression of toxic Arabidopsis thaliana gene products in Saccharomyces cerevisiae was evaluated as a genetic selection scheme. The screening method was tested on a fraction of a cDNA expression library and led to the identification of two Arabidopsis cDNA clones that were toxic to yeast; one corresponded to histone H1 and the other to a previously unidentified gene. This new gene, named ATL2, combines a RING-like zinc-binding motif and a putative signal anchor sequence for membrane insertion in the same molecule. Furthermore, inspection of the 3' untranslated region reveals two types of sequences which appear to be key determinants in rapid transcript decay. Indeed, rapid and transient accumulation of transcript occurs in the presence of a protein synthesis inhibitor and of the growth regulator auxin. These features provide evidence that ATL2 is an early-response gene. Thus, ATL2 represents one of the first early-response plant genes to be described which possesses a distinct regulatory domain; the fact that ATL2 mRNA is induced by auxin suggests that it might have a role during the response of plants to this growth regulator.


Ezetimibe/simvastatin compared with atorvastatin or rosuvastatin in lowering to specified levels both LDL-C and each of five other emerging risk factors for coronary heart disease: Non-HDL-cholesterol, TC/HDL-C, apolipoprotein B, apo-B/apo-A-I, or C-reactive protein.
Recent evidence suggests that in addition to low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (Apo-B), non-high-density lipoprotein cholesterol (non-HDL-C), some lipoprotein ratios, and C-reactive protein (CRP) are predictive of coronary heart disease (CHD) risk. This post-hoc analysis of two trials comparing single-tablet ezetimibe/simvastatin (EZE/SIMVA) to atorvastatin (ATORVA) or rosuvastatin (ROSUVA) evaluates the proportion of patients attaining LDL-C <70 mg/dL and specific levels of these emerging risk factors. These were double-blind, 6-week, parallel group trials of hypercholesterolemic patients randomized to milligram equivalent doses of ATORVA versus EZE 10 mg/SIMVA, or to usual starting, next higher, and maximum doses of ROSUVA versus EZE/SIMVA. This analysis examined the percent of patients in prespecified dose comparisons and overall achievement of LDL-C <70 mg/dL and/or Apo-B <90 mg/dL, total cholesterol (TC)/HDL-C <4.0, or Apo-B/Apo-A-I <0.7 among all treated patients, non-HDL-C <100 mg/dL among patients with baseline triglycerides ≥200 mg/dL, or CRP <2.0 mg/L among patients with baseline CRP ≥2.0 mg/L. Within each trial, baseline characteristics were similar among groups. At all dose comparisons, significantly more patients receiving EZE/SIMVA reached LDL-C <70 mg/dL and achieved both LDL-C <70 mg/dL and either Apo-B <90 mg/dL, TC/HDL-C <4.0, or Apo-B/Apo-A-I <0.7 (EZE/SIMVA versus ATORVA) compared to ATORVA and ROSUVA. For most dose comparisons, significantly more patients receiving EZE/SIMVA attained both LDL-C <70 mg/dL and either non-HDL-C <100 mg/dL or CRP <2 mg/L compared to ATORVA or ROSUVA. The greater efficacy related to changes in blood lipids of EZE/SIMVA compared with both ATORVA and ROSUVA extends to changes in many emerging risk factors. Ultimate clinical implications of these findings still need to be defined.


Characterization of the variability of a 75-kDa membrane protein in Mycoplasma hominis.
The gene p75 encoding a 75-kDa surface-exposed membrane protein P75 was cloned and sequenced from Mycoplasma hominis type strain PG21T. To investigate the intraspecies variability, sequences were obtained from an additional two isolates 7488 and 183, and the three sequences were compared. The nucleotide and amino acid differences were not confined to specific regions of the gene/protein, but when comparing the three sequences, differences were present as single site substitutions or small insertions or deletions of nucleotides/amino acids. The intraspecies variability was further investigated by restriction enzyme analysis with two restriction enzymes (Alul and MboII) of PCR products amplified from p75 from 28 M. hominis isolates. On the basis of band patterns produced by the two restriction enzymes, the isolates could be divided into five and six groups. These groups neither matched categories of the M. hominis vaa gene nor the M. hominis p120 gene classes, indicating that the three genes vary by different mechanisms and possibly indicating horizontal gene transfer. Federation of European Microbiological Societies.


In vitro hepatic conversion of the anticancer agent nemorubicin to its active metabolite PNU-159682 in mice, rats and dogs: a comparison with human liver microsomes.
We recently demonstrated that nemorubicin (MMDX), an investigational antitumor drug, is converted to an active metabolite, PNU-159682, by human liver cytochrome P450 (CYP) 3A4. The objectives of this study were: (1) to investigate MMDX metabolism by liver microsomes from laboratory animals (mice, rats, and dogs of both sexes) to ascertain whether PNU-159682 is also produced in these species, and to identify the CYP form(s) responsible for its formation; (2) to compare the animal metabolism of MMDX with that by human liver microsomes (HLMs), in order to determine which animal species is closest to human beings; (3) to explore whether differences in PNU-159682 formation are responsible for previously reported species- and sex-related differences in MMDX host toxicity. The animal metabolism of MMDX proved to be qualitatively similar to that observed with HLMs since, in all tested species, MMDX was mainly converted to PNU-159682 by a single CYP3A form. However, there were marked quantitative inter- and intra-species differences in kinetic parameters. The mouse and the male rat exhibited V(max) and intrinsic metabolic clearance (CL(int)) values closest to those of human beings, suggesting that these species are the most suitable animal models to investigate MMDX biotransformation. A close inverse correlation was found between MMDX CL(int) and previously reported values of MMDX LD(50) for animals of the species, sex and strain tested here, indicating that differences in the in vivo toxicity of MMDX are most probably due to sex- and species-related differences in the extent of PNU-159682 formation.


Rounded atelectasis of the lung, just a benign disorder.
Three patients with rounded atelectases are described. One of them developed a malignant non-Hodgkin lymphoma 6 months after presentation with rounded atelectasis. His rounded atelectasis could be followed during 20 months and was unrelated to the appearance, complete remission after chemotherapy and relapse of a malignant non-Hodgkin lymphoma. Rounded atelectasis of the lung is a little-known form of peripheral pulmonary collapse which may mimic a neoplastic tumour. It might be formed either because of a folding in a basal lung segment caused by temporarily pleural effusion, or because of initial damage to the pleura which leads to fibrosis and thus to challenge to the clinician, it should be emphasized that the benign nature of rounded atelectasis should be recognized by radiological techniques.


Antepartum fetal heart rate recording and subsequent fast transmission by a distributed microprocessor-based dedicated system.
Fetal heart rate monitoring in high-risk pregnancies can require admission to hospital over prolonged periods, or the even less satisfactory alternative of routine weekly or sporadic outpatient monitoring. We have developed a digital system for distant fetal heart rate recording with the facility of later rapid transmission by telephone into the hospital. A completed half-hour recording is transmitted to the central computer and permanently stored in less than 30 s, then immediately displayed for verbal reporting. One hundred and seventeen recordings have been made in 27 patients' homes and of these 111 (95%) were easy to interpret. This expandable system meets the major functional requirements for practical and economical antenatal fetal heart rate monitoring at a distance.


Effect of combined administration of a synthetic low-toxicity lipid A derivative, DT-5461a, and indomethacin in various experimental tumor models of colon 26 carcinoma in mice.
We investigated the antitumor effects of a synthetic lipid A derivative, DT-5461a, in combination with indomethacin in three experimental tumor models (peritoneal carcinomatosis, liver tumor, and lung tumor models) of transplanted colon 26 carcinoma in mice. This carcinoma produces the immunosuppressive prostaglandin E2 (PGE2). Intravenous administration of DT-5461a alone resulted in little or no prolongation of survival time [increase in life span (ILS): -2%-22%]. When indomethacin was given in drinking water a slight or moderate increase in survival time was seen (ILS: 4%-45%). In contrast, the combination of DT-5461a and indomethacin induced an additive increase in life span (ILS: 16% to more than 193%). The strongest antitumor effect of this combined therapy was seen in the peritoneal carcinomatosis model; in this model, plasma PGE2 concentrations were considerably higher than in normal mice, and concentrations were further but transiently increased by DT-5461a administration. Following oral indomethacin administration, these elevated PGE2 concentrations were reduced to the level in untreated normal mice. Furthermore, intratumoral tumor necrosis factor (TNF) activity in the group receiving the combined therapy was significantly higher than that in the DT-5461a-treated group. No TNF production was induced by the administration of indomethacin alone. These results suggest that the antitumor effect of DT-5461a can be enhanced by combination with indomethacin, and that the inhibition of PGE2 production may have a role in this antitumor effect.


Chemokine CCL24 promotes the growth and invasiveness of trophoblasts through ERK1/2 and PI3K signaling pathways in human early pregnancy.
Chemokine CCL24, acting through receptor CCR3, is a potent chemoattractant for eosinophil in allergic diseases and parasitic infections. We recently reported that CCL24 and CCR3 are co-expressed by trophoblasts in human early pregnant uterus. Here we prove with evidence that steroid hormones estradiol (E), progesterone (P), and human chorionic gonadotropin (hCG), as well as decidual stromal cells (DSCs) could regulate the expression of CCL24 and CCR3 of trophoblasts. We further investigate how trophoblast-derived CCL24 mediates the function of trophoblasts in vitro, and conclude that CCL24/CCR3 promotes the proliferation, viability and invasiveness of trophoblasts. In addition, analysis of the downstream signaling pathways of CCL24/CCR3 show that extracellular signal-regulated kinases (ERK1/2) and phosphoinositide 3-kinase (PI3K) pathways may contribute to the proliferation, viability and invasiveness of trophoblasts by activating intracellular molecules Ki67 and matrix metallopeptidase 9 (MMP9). However, we did not observe any inhibitory effect on trophoblasts when blocking c-Jun N-terminal kinase (JNK) or p38 pathways. In conclusion, our data suggests that trophoblast-derived CCL24 at the maternal-fetal interface promotes trophoblasts cell growth and invasiveness by ERK1/2 and PI3K pathways. Meanwhile, pregnancy-related hormones (P and hCG), as well as DSCs could up-regulate CCL24/CCR3 expression in trophoblasts, which may indirectly influence the biological functions of trophoblasts. Thus, our results provide a possible explanation for the growth and invasion of trophoblasts in human embryo implantation.


Electrode Edge Effects and the Failure Mechanism of Lithium-Metal Batteries.
The very high specific capacity of Li metal makes it an ideal anode for high-energy batteries. However, Li dendrite growth and the formation of isolated (or "dead") Li during repeated Li plating/stripping processes leads to a low coulombic efficiency (CE). In this work, we discovered, for the first time, that electrode edge effects play an important role in the failure of Li-metal batteries. The dead Li formed on the edge of Cu substrate was systematically investigated through SEM, energy-dispersive X-ray (EDX) spectroscopy, and 2D X-ray photoelectron spectroscopy (XPS). To minimize the Li loss at the edge of the Cu exposed to pressure-free space, a modified Li∥Cu cell configuration with a Cu electrode smaller than Li metal is preferred. It was clearly demonstrated that using an electrode configuration with a minimal open space or pressure-free space across electrodes can reduce accumulation of dead Li during cycling and increase Li CE. This phenomenon was also verified in Li-metal batteries (Li∥LiNi1/3 Mn1/3 Co1/3 O2 ) and should be considered in the design of practical Li-metal batteries.


36Cl fluxes in dispersed rat submandibular acini: effects of Ca2+ omission and of the ionophore A23187.
Transmembrane fluxes of 36Cl were investigated in dispersed acini of the rat submandibular gland in Ca2+-containing and Ca2+-free media and also in the presence of the divalent cation ionophore A23187. In Ca2+-replete medium, a time-dependent uptake of tracer resulted in a steady state 36Cl content of 8.5 +/- 0.3 nmol/mg protein in 3-5 min. This uptake was reduced 32% by 1 mM furosemide and 27% by 1 microM acetylcholine. In the presence of Ca2+, the ionophore (10(-5) M) reduced tracer uptake 36% and prevented further effects of either acetylcholine or furosemide. Both acetylcholine and A23187 caused a rapid net efflux of 36Cl from tracer-preloaded acini in Ca2+-containing medium (37% and 20%, respectively). When Ca2+ was omitted from the incubation medium, basal 36Cl uptake in the absence of added test substance was the same as in Ca2+-containing medium but was not affected by acetylcholine, while it was still reduced 29% by furosemide. Addition of acetylcholine to preloaded acini in Ca2+-free medium caused only a transient and unsustained 36Cl efflux but subsequent addition of Ca2+ produced a 36% reduction in tracer content. The ionophore caused a net 36Cl efflux in Ca2+-containing medium (24% decrease in 36Cl content) but had no effect in Ca2+-free medium. Subsequent addition of Ca2+ resulted in a 27% net efflux of tracer. The calmodulin inhibitor trifluoperazine caused a 14% increase in 36Cl uptake but did not cause 36Cl efflux from preloaded cells or modify acetylcholine-induced efflux of tracer from these cells.(ABSTRACT TRUNCATED AT 250 WORDS)


Sequential therapy involving an early switch from entecavir to pegylated interferon-α in Japanese patients with chronic hepatitis B.
The optimal combination of two currently available agents with different mechanisms of action, a nucleos(t)ide analog and pegylated interferon-α (PegIFNα), must be determined to improve treatment of chronic hepatitis B (CHB). In this study, 24 patients with CHB (14 hepatitis B envelope antigen [HBeAg]-positive patients and 10 HBeAg-negative patients) received entecavir for 36-52 weeks, followed by entecavir plus Peg-IFNα2a for 4 weeks, and finally by PegIFNα-2a alone for 44 weeks. A sustained biochemical, virologic, and serologic response was obtained in 7/24 (29%) patients at 48 weeks post-treatment (2/14 [14%] in HBeAg-positive vs 5/10 [50%] in HBeAg-negative patients, P = 0.085). At baseline, patients with a sustained response had a significantly lower γ-glutamyl transferase level (P = 0.0023), a lower aspartate aminotransferase-to-platelet ratio index (P = 0.049), and a lower α-fetoprotein level (P = 0.042) than those without a sustained response. The decline in hepatitis B surface antigen (HBsAg) levels during the first 24 weeks of PegIFNα-2a treatment in patients with a sustained response was greater than that in patients without (P = 0.017). Additionally, HBsAg seroclearance was achieved in two patients (8.3%): one HBeAg-positive and one HBeAg-negative patient. The outcomes of sequential therapy involving an early switch from entecavir to PegIFNα-2a were unsatisfactory in Japanese patients with CHB. In addition to viral factors, host metabolic characteristics and liver fibrosis/tumor markers can be used for prediction of a sustained response to therapy, but accurate prediction of the therapeutic response is difficult.


Partial deletion of the Y chromosome removes the effect of paternal genome imprinting on periovum sensitivity to hyaluronidase in mice.
Cumulus-oocyte complexes from the two consomic strains of mice, B10.BR and B10.BR-Ydel (with a partial deletion of the Y chromosome) and the BALB/c strain, as well as reciprocal F1 and F2 hybrids, were tested for their susceptibility to attack by hyaluronidase. The cumulus cell dispersal was significantly more rapid in the eggs of B10.BR females and of F1 and F2 hybrid females sired by the B10.BR males than in those of BALB/c females and hybrids sired by BALB/c males. These results confirm the earlier data of Bander et al. (1989) which were interpreted as evidence of paternal imprinting of the C57BL genome. In contrast, cumulus cell dispersal in the eggs of females sired by B10.BR-Ydel males was significantly slower than in females sired by B10.BR males, and did not differ from that in the BALB/c strain. The results suggest that the partial deletion of the Y chromosome abolished the effect of paternal genome imprinting which is observed in the B10.BR strain.


Partitioning behavior of heavy metals and persistent organic pollutants among feto-maternal bloods and tissues.
Heavy metals and persistent organic pollutants (POPs), including Pb, Cd, T-Hg, MeHg, PCDD/Fs, PCBs, PBDEs, PCNs, and PBDD/Fs, were analyzed in 20 paired samples of cord blood, maternal blood, maternal urine, and placenta. The samples were collected from pregnant mothers and neonates from South Korea in 2010. The distribution of heavy metals among the samples varied with their physicochemical characteristics. The concentrations of Pb and Hg in the maternal and the cord blood samples were significantly correlated each other, implying efficient transplacental transport (TPT). Cd and Hg were accumulated in the placenta, forming protein conjugates, and T-Hg was higher in the cord blood samples than the maternal blood samples due to the binding affinity of Hg with fetal proteins. POPs generally showed the highest concentrations in the maternal serum samples, and the POPs levels in the cord serum and the placenta samples were dependent on the degree of halogenation. The TPT of POPs was seemingly related to lipoprotein transportation. Some PBDE congeners, however, showed their highest concentrations in the cord serum samples, suggesting an additional TPT mechanism. This is the first study to detect PCNs and PBDD/Fs in the cord serum samples, showing that the PCN levels were comparable to other POPs. According to the principal component analysis (PCA) results of the contaminant levels, POPs and heavy metals showed significantly different characteristics, whereas PBDEs had an intermediate attribute. Despite the limited number of participants, the comprehensive analysis of trace contaminants in the paired sample sets enabled us to infer the distribution and TPT mechanism of various contaminants.


Safety and efficacy of velaglucerase alfa replacement therapy for patients with type 1 Gaucher disease.
Gaucher disease is a multisystem disorder caused by deficiency of β-glucocerebrosidase. Exogenously delivered enzyme replacement therapy (ERT) is currently standard of care. Since 1994, intravenously delivered recombinant ERT with imiglucerase (Cerezyme; Genzyme Corporation, Cambridge, MA, USA) improves hematological, visceral and skeletal features of Gaucher disease at dosages of 15-60 units/kg bodyweight/infusion, administered every other week (EOW). Velaglucerase alfa (VPRIV®; Shire HGT, MA, USA) is a human wild-type-sequenced ERT produced in human cell lines using proprietary Gene-Activation® technology (Shire HGT). This article describes the results of a Phase I/II seminal trial in treatment-naive non-neuronopathic patients (including stepwise dose reduction to 30 units/kg/EOW) and three Phase III trials (two doses: 45 or 60 units/kg/EOW; switch-over from imiglucerase at identical dose; head-to-head with imiglucerase, 60 units/kg/EOW) and Phase III extension trial. Velaglucerase alfa was approved in 2010 in many countries; based on clinical trial experience, it is safe and effective in treatment-naive and switch-over patients, children and adults, splenectomized patients and those with an intact spleen.


Nutritional strategies to optimize training and racing in middle-distance athletes.
Middle-distance athletes implement a dynamic continuum in training volume, duration, and intensity that utilizes all energy-producing pathways and muscle fibre types. At the centre of this periodized training regimen should be a periodized nutritional approach that takes into account acute and seasonal nutritional needs induced by specific training and competition loads. The majority of a middle-distance athlete's training and racing is dependant upon carbohydrate-derived energy provision. Thus, to support this training and racing intensity, a high carbohydrate intake should be targeted. The required energy expenditure throughout each training phase varies significantly, and thus the total energy intake should also vary accordingly to better maintain an ideal body composition. Optimizing acute recovery is highly dependant upon the immediate consumption of carbohydrate to maximize glycogen resynthesis rates. To optimize longer-term recovery, protein in conjunction with carbohydrate should be consumed. Supplementation of beta-alanine or sodium bicarbonate has been shown to augment intra- and extracellular buffering capacities, which may lead to a small performance increase. Future studies should aim to alter specific exercise (resistance vs. endurance) and/or nutrition stimuli and measure downstream effects at multiple levels that include gene and molecular signalling pathways, leading to muscle protein synthesis, that result in optimized phenotypic adaptation and performance.


Invasive lobular carcinoma of the breast: mammographic characteristics and computer-aided detection.
To characterize the mammographic appearance of invasive lobular carcinoma in a large series of screening-detected consecutive breast cancers and to evaluate the ability of a computer-aided detection system to mark these carcinomas. Investigators used the Breast Imaging Reporting and Data System lexicon to characterize lesions as part of a retrospective review of 90 screening mammographic examinations that led to biopsy-proved diagnosis of 94 invasive lobular carcinoma lesions. The 40 available prior mammographic examinations (obtained 9-24 months earlier) were also reviewed to characterize any visible findings. The results of a computer-aided detection analysis were compared with the images, and the sensitivity of the algorithm was calculated for correct detection of the lesions. Fifty-six (60%) of 94 lesions manifested as masses, of which 40 (71%) were described as irregular and spiculated; 20 (21%) of 94, as architectural distortions; and the remainder, 18 (20%), as either asymmetric densities or calcifications. On the screening mammograms showing biopsy-proved cancers, the sensitivity of the computer-aided detection system was 86 (91%) of 94 lesions. Thirty-one of the 40 prior mammograms showed retrospectively visible findings, and 24 (77%) of 31 were marked by the computer-aided detection system. Spiculated masses and architectural distortions are the predominant appearances of invasive lobular carcinoma, and a computer-aided detection system correctly marked a high percentage of invasive lobular carcinoma lesions.


Predictors of the clinical outcome and survival without degenerative arthritis after surgical treatment of femoroacetabular impingement.
The main purposes of the present study were to evaluate the functional improvement, to identify the predictors of the clinical outcome after open surgical management of femoroacetabular impingement (FAI) in mid-term, and to determine 5-year survival rate. In this retrospective study, the clinical data of 33 patients (34 hips) were evaluated. Sex, age, body mass index (BMI), type of FAI, duration of symptoms up to surgical treatment, internal rotation of the affected hip, improvement of the Harris hip score (HHS) in the first 2 years, joint space narrowing evaluated radiographically and classified according to Kellgren-Lawrence classification, and any labral tear were the independent variables. Harris hip score and degenerative arthritic changes at the latest follow-up were identified as outcome measures. Univariate and multivariate analyses were performed. The mean post-operative follow-up was 6 years. Harris hip scores at the latest follow-up were significantly worse in patients with a pre-operative age >35 years, BMI ≥25 kg/m2, internal rotation of the hip ≤10°, grade 1 or 2 joint space narrowing, labral tear, and <15 points improvement of the HHS at the first 2 years follow-up. According to multivariate analysis; major predictors of the outcome were BMI, labral tear, and improvement of the HHS at the first 2 years. A pre-operative BMI ≥25 kg/m2, labral tear, and <20 points improvement of the HHS in the first 2 years of surgery should be considered as the major predictors of the clinical outcome after open surgical management of idiopathic FAI.


Growth and nutritional status in infants with short-bowel syndrome after the serial transverse enteroplasty procedure.
The aim of this study was to describe the long-term nutritional outcomes of 4 patients with short bowel syndrome (SBS) who underwent a newly described bowel-lengthening procedure, the serial transverse enteroplasty (STEP) procedure. We performed a retrospective review of the medical records of 4 children who underwent STEP at 1 center. The primary outcome measure was the percentage of total dietary energy received by the enteral route before and after STEP. Other outcome measures were weight and height Z scores and body composition, as measured by arm anthropometric values. Four children with SBS were identified, all of whom had been dependent on parenteral nutrition since birth. The mean preoperative follow-up period was 234 days (range, 63-502 days), and the mean postoperative follow-up period was 362 days (range, 252-493 days). By using model-based mean estimates, the mean enteral nutrition intake was 48% preoperatively vs 62% postoperatively (P = .02). The model mean weight for age Z score increased by .7 SDs postoperatively (P = .01), and the model mean weight for height increased by .6 SDs (P < .0001). The percent standard mid-upper-arm circumference increased by 13.1% postoperatively (P = .03), and the percent standard triceps skinfold increased by 24.5% postoperatively (P < .0001). The STEP procedure was associated with improved growth and body composition among 4 children with SBS in the face of a decreasing need for parenteral nutrition. Among patients with refractory SBS and dilated small intestine, the STEP procedure is associated with improved clinical and nutritional outcomes in the first year after surgery.


Discrimination of Bordetella parapertussis and Bordetella pertussis organisms from clinical isolates by PCR using biotin-labelled oligonucleotide probes.
A recently developed shared-primer polymerase chain reaction (PCR) was investigated, in an ongoing pertussis surveillance study for discrimination of Bordetella parapertussis and Bordetella pertussis organisms, by using specific biotin-labelled oligonucleotide probes. From a total of 132 samples, 83 were positive by the B. parapertussis specific probe, 33 were positive by the B. pertussis specific probe and 16 samples containing Hemophilus influenzae as a negative control were below threshold by both probes. The shared-primer PCR in combination with specific oligonucleotide probes provides a rapid, sensitive and specific molecular diagnostic tool for future surveillance studies. In addition, it may be used to further investigate whether B parapertussis antigens should be added to acellular pertussis vaccines to protect against B. parapertussis infections.


Clinical and microbiologic determinants of serious bloodstream infections in Egyptian pediatric cancer patients: a one-year study.
Bloodstream infections (BSI) remain a major cause of morbidity and death in patients undergoing treatment for cancer. However, all recent epidemiological and therapeutic studies underline the absolute need for knowledge of the factors governing the infections in each center. The aim of this study is to identify the factors affecting BSI in the pediatric service of the National Cancer Institute (NCI) at Cairo University. More tailored policies for the treatment of patients with febrile neutropenia following chemotherapy can then be created. Over a 12-month period, all children with cancer and fever, with or without neutropenia, who were admitted to the NCI for empirical therapy of febrile episodes and who had a microbiologically confirmed bloodstream infection were studied retrospectively. A total of 328 BSI occurred in 1135 febrile episodes in pediatric cancer patients at the NCI in one year. Gram-positive bacteria were isolated in 168 episodes (51.2%) and 61.9% of the total isolates (either single or mixed), Gram-negative in 97 (29.6%), and mixed infections in 45 (13.7%). The common causative agents of bloodstream infections in this study were coagulase-negative staphylococci (16.2%), Staphylococcus aureus (13.4%), Streptococcus spp. (12.1%) followed by Acinetobacter spp. (6.7%) and Pseudomonas spp. (5.5%). Fungemia was encountered in 18 episodes, being mixed in nine of them. A more serious BSI in terms of a prolonged episode was encountered in 30.2% of the episodes and was significantly associated with patients being hospitalized, having intensified chemotherapy, polymicrobial and fungal infection, lower respiratory tract infections and persistent neutropenia at day seven. In a large population of children, common clinical and laboratory risk factors were identified that can help predict more serious BSI. These results encourage the possibility of a more selective management strategy for these children.


Genomic parallelism and lack thereof in contrasting systems of three-spined sticklebacks.
Parallel evolution and the extent to which it involves gene reuse have attracted much interest. Whereas it has theoretically been predicted under which circumstances gene reuse is expected, empirical studies that directly compare systems showing high and low parallelism are rare. Three-spined stickleback (Gasterosteus aculeatus), where freshwater populations have been independently founded by ancestral marine populations, represent prime examples of phenotypic and genomic parallelism, but cases exist where parallelism is low. Based on RAD (restriction site associated DNA) sequencing, we analysed SNPs and chromosome inversions in populations in Denmark and Greenland showing low and high parallelism, respectively. We identified parallelism across freshwater populations in Greenland at genomic regions previously identified to be associated with marine-freshwater divergence. These same markers also separated Danish marine and freshwater sticklebacks, albeit to a weaker extent. Hence, parallelism was not absent in Denmark but possibly constrained by spatially and temporally varying selection. Divergence time estimates found one Danish freshwater population to be much older than the others. It also deviated strongly with respect to parallelism and may represent earlier postglacial colonization based on a different pool of standing variation and eliciting different adaptive responses to freshwater conditions. These findings provide empirical support to previous suggestions that the time since replicate populations had access to a common pool of standing variation is a major factor determining gene reuse. At last, based on the observed parallelism in the Greenlandic system we discuss the predictability of adaptive responses in newly established populations.


Inhibition of rat brain microsomal Na+,K+-ATPase by S-adenosylmethionine.
Rat brain microsomes were preincubated with S-adenosylmethionine (SAM), MgCl2, and CaCl2, then reisolated, and the activity of Na+,K+-ATPase determined. SAM inhibited the Na+,K+-ATPase activity compared with microsomes subjected to similar treatment in the absence of SAM. A biphasic inhibitory effect was observed with a 50% decrease at a SAM concentration range of 0.4 microM-3.2 microM and a 70% reduction at a concentration range above 100 microM. Inclusion of either S-adenosylhomocysteine or 3-deazaadenosine in the preincubations prevented the SAM inhibition of Na+,K+-ATPase activity. The inhibition by SAM appeared to be Mg2+- or Ca2+-dependent.


Echocardiographic assessment of right and left ventricular function after single-lung transplantation.
To evaluate the impact of single-lung transplantation on right and left ventricular performance and to identify potential preoperative characteristics that could predict postoperative outcome, a large group of patients were retrospectively evaluated by means of serial Doppler echocardiography. Twenty-six of 57 consecutive single-lung transplant patients had satisfactory Doppler echocardiographic studies before and after surgery. A significant reduction in right ventricular diastolic and systolic areas and an increase in right ventricular fractional area were noted after transplantation. The left ventricular contractility remained unchanged. In addition, significant reduction in right atrial area, right ventricular free wall thickness, and tricuspid regurgitation were also seen. Paradoxical septal motion present in eight patients before the procedure resolved in all of them after single-lung transplantation. Transthoracic echocardiography is a useful technique to document improvement in right ventricular function in 63% of patients following single-lung transplantation. Preoperative paradoxical septal motion identifies single-lung transplant recipients who have the largest postoperative right ventricular area reduction and fractional area increase. Alternative imaging modalities should be sought for single-lung transplant candidates in whom conventional transthoracic echocardiography is suboptimal.


Oxidative stress and endothelial dysfunction in cerebrovascular disease.
Maintenance of vascular tone by the endothelium involves the production of endothelium-derived nitric oxide (NO). NO, produced from endothelial nitric oxide synthase diffuses to the underlying smooth muscle to stimulate soluble guanylate cyclase, resulting in increased cyclic GMP levels, and subsequent smooth muscle relaxation and blood vessel dilatation. Endothelial dysfunction, manifested as diminished NO bioavailability, is a common feature of a number of vascular-related diseases.. Oxidative stress can be defined as an imbalance between reactive oxygen species (ROS) production and/or impaired ROS metabolism that favours them being present in excess of physiological levels. Oxidative stress can negatively impact many cell types, including in the vasculature. There is now a wealth of evidence suggesting that oxidative stress is a major cause of endothelial dysfunction in the cerebral circulation. This review will summarize disease models in which both oxidative stress and endothelial dysfunction occur in the cerebral circulation, namely hypertension involving angiotensin II (Ang II), diabetes, subarachnoid hemorrhage, stroke and Alzheimer's disease. Molecular mechanisms by which oxidative stress occurs, (eg increased NADPH-oxidase activity) will also be discussed.


Skin damage probabilities using fixation materials in high-energy photon beams.
Patient fixation, such as thermoplastic masks, carbon-fibre support plates and polystyrene bead vacuum cradles, is used to reproduce patient positioning in radiotherapy. Consequently low-density materials may be introduced in high-energy photon beams. The aim of the this study was to measure the increase in skin dose when low-density materials are present and calculate the radiobiological consequences in terms of probabilities of early and late skin damage. An experimental thin-windowed plane-parallel ion chamber was used. Skin doses were measured using various overlaying low-density fixation materials. A fixed geometry of a 10x10 cm field, a SSD=100 cm and photon energies of 4, 6 and 10 MV on Varian Clinac 2100C accelerators were used for all measurements. Radiobiological consequences of introducing these materials into the high-energy photon beams were evaluated in terms of early and late damage of the skin based on the measured surface doses and the LQ-model. The experimental ion chamber gave results consistent with other studies. A relationship between skin dose and material thickness in mg/cm(2) was established and used to calculate skin doses in scenarios assuming radiotherapy treatment with opposed fields. Conventional radiotherapy may apply mid-point doses up to 60-66 Gy in daily 2-Gy fractions opposed fields. Using thermoplastic fixation and high-energy photons as low as 4 MV do increase the dose to the skin considerably. However, using thermoplastic materials with thickness less than 100 mg/cm(2) skin doses are comparable with those produced by variation in source to skin distance, field size or blocking trays within clinical treatment set-ups. The use of polystyrene cradles and carbon-fibre materials with thickness less than 100 mg/cm(2) should be avoided at 4 MV at doses above 54-60 Gy.


Spatial and temporal visual filtering in patients with glaucoma and ocular hypertension.
To investigate the spatial and temporal response characteristics in patients with glaucoma and ocular hypertension (OHT), in order to demonstrate the earliest specific measure of vision loss and to elucidate the precise mechanism of early glaucomatous damage. The Open Optical View System was used to assess changes in spatial and temporal vision in patients with clearly defined glaucoma (30 eyes), patients with OHT (30 eyes) and 30 eye-matched normal control eyes. The psychophysical methods applied were developed by Barber and Ruddock, who showed that the responses called ST1 and ST2 have similar characteristics to those found in the parvocellular and magnocellular pathway respectively. The measurement of spatial and temporal responses rests upon the measurement of a target that moves across a background, itself modulated spatially (gratings) and temporally (flicker). The results reported, taken together with the current data on retinal ganglion cell function, reveal damage to both the parvocellular and magnocellular pathway in patients with glaucoma. In the OHT groups only marginal changes were found in the parvocellular response, but significant changes in the magnocellular response. In both OHT and glaucoma, the temporal processing shows greatest abnormalities at a small number of low flicker frequencies. We provide psychophysical evidence of the detectable ganglion cell damage in patients with OHT who remain normal on testing with automated perimetry. The psychophysical method chosen (which measures the function of specific sub-divisions of the visual pathway) may prove useful in screening for glaucomatous damage.


A comparison of methods for the detection of the r'(s) haplotype.
The r'(s) haplotype is found in 5% to 15% of individuals of African descent. Persons with this haplotype have a partial C antigen and weakened e and can produce anti-C or other "e-like" alloantibodies. Thus, for these chronically transfused patients, accurate detection of the r'(s) haplotype is important for selection of matched units. African-American donors were genotyped using the human erythrocyte antigen (HEA) microarray. Samples (n = 125) identified as "possible r'(s) " were then tested by IDCORE XT and RHD and RHCE microarrays. DNA sequencing was used to resolve discordant samples. The genotyping results were compared to serologic testing using a monoclonal anti-C reagent (Clone MS24). Of the 125 possible r'(s) samples identified by HEA, only 94 (75%) were confirmed by both RHD and RHCE microarrays. The IDCORE XT accurately detected 93 of 94 (99%) of the confirmed r'(s) and had no false positives. DNA sequencing of the one discordant sample revealed the presence of a compound heterozygote with RHD* DIII.4/RHCE*ceVS.02 as one haplotype and r'(s) Type 2 as the other. The 31 unconfirmed r'(s) samples carried RHCE*ceVS.03 not linked to the hybrid RHD-CE-D. This occurred most often with RHD*DIIIa (55%) or RHD*01 (19%) and rarely with DIII.4, DIII.6, DAU3, and weak D Type 14. Serologic testing with anti-C gave 100% concordance with the r'(s) samples. The predominant type of r'(s) in African-Americans is Type 1, which can be detected either by a reagent anti-C containing Clone MS24 or by IDCORE XT. However, serology cannot differentiate between a normal C allele and the hybrid.


Involvement of the endogenous lectin CSL in adhesion of Chinese hamster ovary cells.
Immunochemical localization of an endogenous mannose-binding protein, the cerebellar soluble lectin (CSL; Zanetta et al., J. Neurochem. 49, 1250-1257 (1987)), in Chinese hamster ovary cells indicated its high concentration in areas of contact between cells. This suggested its role in cell adhesion. The pattern of staining differed significantly in the cells cultured in suspension from that grown as monolayer. In cells maintained for a short time as suspension, the extracellular CSL immunoreactivity was found mainly in close apposition to the plasma membrane including contact areas. In cells cultured as monolayer, extracellularly, the lectin was found both at the cell surface and in a 75-nm thick layer between two cells, apparently adhering to the cell surface through bridges. Endogenous glycoprotein ligands of CSL were present in the cultures of CHO cells, both as membrane-bound glycoproteins and as glycoprotein ligands soluble in the presence of mannose in the absence of detergent. The lectin CSL induced adhesion between these cells as evident by low concentration of anti-CSL Fab fragments inhibiting such adhesion. These data suggested that adhesion between CHO cells occurs, in part, through a glycobiological recognition system involving CSL. This mechanism should be taken into account for the interpretation of experiments of transfection in CHO cells of the genes of glycoproteins involved in cell adhesion.


[Chronic orchialgia].
Chronic orchialgia, whose positive signs defy routine examinations, is usually misdiagnosised as chronic prostatitis or a psychological disorder. This paper aims at introducing the definition, etiology, diagnosis and management of chronic orchialgia, as well as a reappraisal and refinement of the traditional treatment of the disease.


Identification of the optimal treatment regimen in the presence of missing covariates.
Covariates associated with treatment-effect heterogeneity can potentially be used to make personalized treatment recommendations towards best clinical outcomes. Methods for treatment-selection rule development that directly maximize treatment-selection benefits have attracted much interest in recent years, due to the robustness of these methods to outcome modeling. In practice, the task of treatment-selection rule development can be further complicated by missingness in data. Here, we consider the identification of optimal treatment-selection rules for a binary disease outcome when measurements of an important covariate from study participants are partly missing. Under the missing at random assumption, we develop a robust estimator of treatment-selection rules under the direct-optimization paradigm. This estimator targets the maximum selection benefits to the population under correct specification of at least one mechanism from each of the two sets-missing data or conditional covariate distribution, and treatment assignment or disease outcome model. We evaluate and compare performance of the proposed estimator with alternative direct-optimization estimators through extensive simulation studies. We demonstrate the application of the proposed method through a real data example from an Alzheimer's disease study for developing covariate combinations to guide the treatment of Alzheimer's disease.


The aftermath of rash action: sleep-interfering counterfactual thoughts and emotions.
A consistent body of evidence suggests that excessive cognitive activity at bedtime is a key factor in insomnia. It is generally assumed that sleep-interfering cognitions are affect laden, but still little is known about the precise nature of the affective processes that are involved. The present study sought to explore the role of counterfactual thinking and counterfactual emotions (regret, shame, and guilt) in insomnia as a function of impulsivity. It was hypothesized that when retiring for the night, individuals scoring high on urgency review their rash daytime behavior and are therefore likely to engage in counterfactual thinking and to experience associated feelings of regret, shame, and guilt. A sample of 101 undergraduate students completed three questionnaires: the UPPS Impulsive Behavior Scale, the Bedtime Counterfactual Processing Questionnaire, and the Insomnia Severity Index. Results indicated that both urgency and counterfactual processing were related to insomnia severity and that the effect of urgency on insomnia was mediated by counterfactual processing. These findings reveal for the first time that impulsivity relates to counterfactual cognitive-affective processing and that this type of processing contributes to sleep disturbances.


Zn ion post-implantation-driven synthesis of CuZn alloy nanoparticles in Cu-preimplanted silica and their thermal evolution.
Cu nanoparticles (NPs) were fabricated in silica by 45 keV Cu ion implantation at a fluence of 1.0 × 10(17) cm(-2) and were then subjected to implantation of 50 keV Zn ions at fluences of 1.0 × 10(16), 5.0 × 10(16), and 10.0 × 10(16) cm(-2), respectively. Our results clearly show that post Zn ion implantation could significantly modify structures and components of the preformed Cu NPs and thus the corresponding surface plasmon resonance (SPR) absorption can be modulated in a wide range. In particular, CuZn alloy NPs with unique SPR absorption were synthesized in Cu-implanted silica followed by Zn ion implantation at a fluence of 5.0 × 10(16) cm(-2). During subsequent annealing, two distinguished processes concerning CuZn alloy NPs (i.e., realloying and dealloying) were found that directly result from thermally driven diffusion of Zn atoms. Moreover, owing to Zn diffusion, lots of core-shell nanostructures consisting of Zn-related compound shells around Cu cores were observed after annealing at 500 °C and higher. The underlying mechanism concerning the formation and decomposition of CuZn alloy NPs is discussed and presented.


Characterization of bacterial genospecies by computer-assisted statistical analysis of enzyme electrophoretic data.
A computer-assisted statistical treatment of the electrophoretic data obtained from the analysis of two dehydrogenases and 27 kinds of esterases produced by strains belonging to the taxonomically complex genus Acinetobacter is described. The 12 genospecies were clearly separated from each other by correspondence analysis. For each genospecies the distances of the strains from their barycenter were computed and typical isolates suitable for use as reference strains were determined. This approach is suitable for the systematic study of other procaryotic or eucaryotic organisms.


Biocompatibility of alendronate-loaded acrylic cement for vertebroplasty.
This paper reports a biological evaluation of a non-resorbable acrylic cement loaded with alendronate for the treatment of osteoporotic vertebral compression fractures. The cement formulation was based on polymethyl methacrylate and acrylic monomers; one of these had covalently linked vitamin E residues. The same cement in the absence of alendronate was used as a control. The setting of the charged cement presented a maximum polymerization temperature of 44°C, a setting time of 24 min, a residual monomer content lower than 3 wt.%, a compressive strength of 99±10 MPa and an elastic modulus of 1.2±0.2 GPa. Cytotoxicity studies using human osteoblast cultures revealed that the leachable substances of the alendronate loaded cement collected between 1 and 7 days decreased cell viability to values lower than 80%. However, morphological changes and cellular damage in cells produced by the extracts decreased with the leak time. Cell adhesion and growth on charged cement was significantly lower than on the control. Implantation of the cement paste in the intra-femoral cavity of rabbits showed that initially the osteogenic activity was evident for the cement charged with alendronate, and the osteosynthesis process took place mainly in the trabeculae and was manifested by the presence of a non-mineralised osseous spicule. The interface between material and adjacent bone tissue was initially characterized by a variable fibrous response that in many cases it appeared reduced to thin connective tissue after a 24-week-period.


Acute myelogenous leukaemia following cytotoxic therapy: five cases and a review.
Acute myelogenous leukaemia (AML) following cytotoxic chemotherapy has been reported increasingly. Five new cases are presented including the first described following treatment for immune thrombocytopaenia. A review of the literature has revealed 226 case reports of treatment-linked AML with sufficient detail to permit further study. Of the total of 231 patients, 76 (33 per cent) followed Hodgkin's disease, 59 (25.5 per cent) multiple myeloma, 22 (9.5 per cent) non-Hodgkin's lymphoma, 32 (14 per cent) other solid tumours and 42 (18 per cent) non-malignant diseases. The time interval from the start of chemotherapy to the diagnosis of AML was similar in all disease groups whether the patients had received radiotherapy or not. Differences emerged when the duration of exposure to chemotherapy was analysed in the individual disease groups; exposure was shorter in those patients treated for Hodgkin's disease and solid tumours than with the others suggesting that the pattern of administration of chemotherapy may be important. The effects of radiotherapy in addition to chemotherapy could not be defined precisely, but the study highlights the particular risk that appears to arise from alkylating agents, and the need to define optimal methods of administration of chemotherapy with minimal risk of inducing leukaemia.


[Ligation of the vena dorsalis penis profunda in treating vascular-induced impotence].
It is reported on the diagnosis and treatment of vasculogeneic impotence. With the use of dynamic cavernosography in 6 patients changes in the venous system were detected and therefore the profound dorsal penile vein was ligated. In 4 patients the sexual function could be improved. The results are encouraging in the case of safe diagnosis and adequate operative treatment.


Determination of pesticide residues in Turkey's table grapes: the effect of integrated pest management, organic farming, and conventional farming.
Turkey is one of the world's largest producers and exporters of table grapes. Growing social concerns over excessive pesticide use have led to farming to move from conventional to organic practices. Table grapes were collected from 99 different farms in three Aegean regions. Pesticide residues were only detected in farms using conventional agriculture practices while no pesticides were detected in grapes from farms using organic or integrated pest management. A risk assessment model indicated that lambda-cyhalothrin posed the most significant risk at conventional farms.


High-performance liquid chromatographic method for the enantioselective analysis of mefloquine in plasma and urine.
An HPLC method for analysis of the enantiomers of the antimalarial drug mefloquine is presented. A complete resolution of (-)-(11S,2'R) and (+)-(11R,2'S) erythro-mefloquine from plasma and urine was obtained on a commercial AGP column. Mefloquine enantiomers were detected by UV at 222 nm. The separation factor (alpha) at +20 degrees C was 1.50. The limit of determination (coefficient of variation 4.0%) for the enantiomeric ratio (11S,2'R)/(11R,2'S) is 15:1 at a total mefloquine concentration of 1.6 mM.


Development of a colloidal gold-based immunochromatographic test strip for the rapid, on-site detection of Pseudomonas aeruginosa in clinical samples.
Current procedures for the detection of Pseudomonas aeruginosa require sophisticated equipment, skilled technicians, and a great deal of time. Immunochromatography assays (ICA) are simple and rapid diagnostic procedures that can be performed and interpreted on the spot or at the bedside without a machine. We developed a rapid, 1-step immunochromatographic test strip that is well suited to the on-site detection of P. aeruginosa with high sensitivity and specificity. In brief, a monoclonal antibody targeting the outer membrane protein F (OprF) of P. aeruginosa, 3C3B5, was conjugated to colloidal gold and used as a detection antibody. An OprF polyclonal antibody was developed as the capture antibody. Eighty-three clinical samples were examined for P. aeruginosa by rapid 1-step ICA and compared with Multiplex-polymerase chain reaction (M-PCR). The detection limit of this method is 5 × 10(5) CFU/ml for P. aeruginosa and 10 ng/ml for the OprF protein. The immunochromatographic strip test demonstrated a slightly lower sensitivity (84.8%), but a similar specificity (100%), to multi-PCR, which is an accurate method for the detection of P. aeruginosa in the laboratory. We observed no cross-reactivity with non-P. aeruginosa bacterial microbes. The detection of P. aeruginosa by the ICA strip can be completed within 5-10 min and is at least 10-fold faster than M-PCR. The ICA test strip developed in this study has proved to be a rapid, simple, effective and economical method for the detection of P. aeruginosa infection in clinical samples. To our knowledge, this is the first report of an ICA method being used to detect P. aeruginosa.


Current concepts in concussion: evaluation and management.
Concussion is a disturbance in brain function caused by direct or indirect force to the head. It is a functional rather than structural injury that results from shear stress to brain tissue caused by rotational or angular forces-direct impact to the head is not required. Initial evaluation involves eliminating cervical spine injury and serious traumatic brain injury. Headache is the most common symptom of concussion, although a variety of clinical domains (e.g., somatic, cognitive, affective) can be affected. Signs and symptoms are nonspecific; therefore, a temporal relationship between an appropriate mechanism of injury and symptoms must be determined. There are numerous assessment tools to aid diagnosis, including symptom checklists, neuropsychological tests, postural stability tests, and sideline assessment tools. These tools are also used to monitor recovery. Cognitive and physical rest are the cornerstones of initial management. There are no specific treatments for concussion; therefore, focus is on managing symptoms and return to play. Because concussion recovery is variable, rigid classification systems have mostly been abandoned in favor of an individualized approach. A graded return-to-play protocol can be implemented once a patient has recovered in all affected domains. Children, adolescents, and those with a history of concussions may require a longer recovery period. There is limited research on the management of concussions in children and adolescents, but concern for potential consequences of injury to the developing brain suggests that a more conservative approach to management is appropriate in these patients.


Dielectrophoretic deposition of graphite oxide soot particles.
Alternating current dielectrophoresis in water was used to position graphite oxide soot (GO-soot) particles generated by rapid thermal expansion of graphite oxide under inert gas. The dielectrophoretic deposition was carried out at a frequency of 10 MHz and a peak-to-peak voltage of 10 V, and the deposited particles were analyzed using scanning electron microscopy. The vertical cross section, obtained by focused ion beam cutting, shows the wrinkled layers of the GO-soot particles and cavities between the layers. The electrical transport measurements show typical characteristics of metal-like pathways. The improved electrical contact between electrodes and GO-soot, probably due to the thin platelet structure of GO-soot, makes the material favorable for electrical device applications. The results demonstrate that AC dielectrophoresis can be used to selectively deposit graphite oxide soot particles at desired locations.


Neurovascular anatomical variations in the anterior palate observed on CBCT images.
This study aimed to assess the presence of additional foramina and canals in the anterior palate region, through cone beam computed tomography (CBCT) images, describing their location, direction, and diameter. CBCT exams of 178 subjects displaying the anterior maxilla were included and the following parameters were registered: gender; age group; presence of additional foramina in the anterior palate (AFP) with at least 1 mm in diameter; location and diameter of AFP; and direction of bony canals associated with AFP. Twenty-eight patients (15.7%) presented AFP and in total 34 additional foramina were registered. No statistical differences between patients with or without AFP were found for gender or age. The average diameter of AFP was 1.4 mm (range from 1 to 1.9 mm). Their location was variable, with most of the cases occurring in the alveolar process near the incisors or canines (n = 27). In 18 cases, AFP was associated with bony canals with upward or oblique direction toward the anterior nasal cavity floor. In 14 cases, the canal presented as a direct extension of the canalis sinuosus, in an upward direction laterally to the nasal cavity aperture. In two cases, the canal was observed adjacent to the incisive and joined the nasopalatine canal superiorly. CBCT images have a crucial role in the recognition of anatomical variations by allowing detailed tridimensional evaluations. Additional foramina and canals in the anterior region of the upper jaw are relatively frequent. Practitioners should be aware and trained to identify these variations. Over 15% of the population studied had additional foramina in the anterior palate, between 1 mm and 1.9 mm wide, with variable locations. In most cases the canals associated with these foramina either presented as a direct extension of the canalis sinuosus, or coursed towards the nasal cavity floor.


Hypogammaglobulinemia and Nocardia brain abscesses.
The host defense responses to Nocardia asteroides are not known. We have investigated a patient with common variable adult onset hypogammaglobulinemia who developed fatal disseminated nocardiosis. The patient had low levels of serum immunoglobulins; the total lymphocyte count was normal as were the percentages of circulating T and B cells. Transmission electron microscopic studies demonstrated typical N. asteroides within the brain parenchyma and nonspecific inflammatory changes in the central nervous system. The findings suggest that humoral immunity may play a major role in the host defense of patients with this disease.


[Factors associated with successful smoking cessation among adolescent smokers undergoing a smoking cessation program involving nicotine replacement therapy].
To identify factors associated with successful smoking cessation among adolescent smokers in a smoking cessation program involving nicotine replacement therapy. We recruited adolescent smokers who were prepared to quit smoking and participated in the smoking cessation program in Kanagawa prefecture. All participants fulfilled a questionnaire beforehand, covering gender, age at the beginning of the study, age at onset of smoking, the number of quit attempts, the number of cigarettes per day and the smoking status of their families and friends. Seven nicotine patches (nicotine 52.5 mg/day) were given to them free of charge for daily use. Their smoking status and the use of nicotine patches were confirmed by telephone or postcard at the 1 and 6 month follow-ups. The relationships between successful smoking cessation and different factors among eligible participants were analyzed using the Fisher's exact test and the Mann-Whitney U test. The subjects included 39 adolescent smokers (mean 16.4 years). The mean age at onset of smoking and the mean duration of smoking were 13.3 years and 2.3 years, respectively. The average daily number of cigarettes smoked was 12.8. Of 39 eligible participants at the one month follow up, 14 (35.9%) were found to be abstaining from smoking. The subjects treated with nicotine patches were significantly more likely to be abstinent than those without them (P<0.05). However, no significant associations with other factors were found. Of 39 participants at the six months follow up, 10 (25.6%) were still abstinent but there were no significant associations with any of the factors, including use of nicotine patches. Subjects living with smokers were significantly less likely to be successful in their efforts to quit than those living with non-smokers (P< 0.05). There were no significant associations with other factors, including using nicotine patches. No adverse events relating to the use of the nicotine patches were encountered during the study period. The smoking cessation program involving NRT provided for adolescent smokers appeared effective at the one month follow up. Those adolescents living with smokers had more difficulties in quitting smoking than those with non-smokers at the 6 month follow up. In order to increase the number of adolescent smokers in the smoking cessation study, the need to obtain parental consent might be considered as a barrier to be overcome. Additionally, more effective follow-up procedures should be considered for the purpose of avoiding dropouts during the study.


Viridans streptococcal bacteraemia in patients with neutropenia.
Viridans streptococcal bacteraemia is frequent in neutropenic patients. 25 neutropenic patients with viridans streptococcal bacteraemia were compared with 64 control patients. Exposure to repeated chemotherapy or cytarabine were independent risk-factors for streptococcal bacteraemia. The use of carboxyureidopenicillins and a stay in laminar-airflow rooms were protective. In a further cohort study of 49 patients, oral streptococci with the same ribotype as blood isolates were recovered from all 7 bacteraemic patients. The oral cavity is a portal of entry for viridans streptococci bacteraemia in neutropenic patients, especially after oral mucosal damage induced by repeated chemotherapy.