Prognostic significance of a solid component in pulmonary adenocarcinoma.
We retrospectively analyzed pulmonary adenocarcinoma patient survival in our single-institution database to evaluate the impact of solid adenocarcinoma components (SAC) on survival and to propose a method of incorporating SAC into the T classification in future staging systems. We reviewed 504 consecutive patients with surgically resected pulmonary adenocarcinoma for their clinicopathologic characteristics and prognoses, stratifying patients according to predominant adenocarcinoma subtype. We also stratified patients with an SAC-containing tumor according to the ratio of SAC in analyzing outcome. Patients with SAC (SAC+) had significantly poorer prognoses than patients without any SAC (SAC-), irrespective of SAC ratio. Patient groups stratified by pathologic T classification up to T2b could be divided into four categories according to SAC status in decreasing order of survival: (I) T1a/SAC-; (II) T1b/SAC-; (III) T1a/SAC+, T1b/SAC+, and T2a/SAC-; and (IV) T2a/SAC+ and T2b/SAC-. Pulmonary adenocarcinoma patients with any amount of SAC had worse prognoses than those without any SAC. The presence of SAC was an independent unfavorable prognostic factor, comparable to other pathologic findings indicating invasion. Solid adenocarcinoma component was an upstaging factor in T classification for T1 and T2a pulmonary adenocarcinomas. If SAC is present, we propose T1 and T2a tumors should be classified as T2a and T2b, respectively.


Effects of long-term administration of clodronate on growing rat bone.
Bisphosphonates inhibit bone resorption. Short-term bisphosphonate treatment at therapeutical dosage has been shown to be safe, but there are only a few studies concerning the long-term effects of bisphosphonates on the non-osteoporotic skeleton. Here, we studied the bone effects of 32 weeks' treatment with clodronate on growing rats, using a therapeutical dose of 2 mg/kg and a high dose of 10 mg/kg. We used biomechanical, densitometrical, and, histomorphometrical analyses to examine the rat tibia, femur, and vertebra and also tested some hematological and biochemical parameters. Tibial length was significantly lower in the high clodronate group compared with the controls. No differences were found in tibial or vertebral ash weights. The L4 vertebra compression failure load was higher in the high clodronate group compared with the therapeutical clodronate group, but not compared with the controls. The mechanical strength of the femoral shaft or femoral neck was not affected by clodronate. Cortical BMD in the L4 vertebra was significantly higher in both clodronate groups compared with controls. Histomorphometrical analysis indicated that the trabecular number of vertebra was increased in the therapeutical clodronate group. The mineral apposition rate was not significantly affected by the treatment. Hematological analyses showed a decreased number of platelets at the high dosage. A slight increase in liver enzyme activity was seen in both groups. We conclude that long-term administration of clodronate has no harmful but rather some beneficial effects on bone at the therapeutical dosage. However, a fivefold dose of clodronate causes a slight decrease in the growth of tibial length.


Coupling of low-order LP modes propagating in cylindrical waveguides into whispering gallery modes in microspheres.
Whispering gallery modes in microspheres are excited by light delivered to them via optical fibers imbedded in a half-block coupler. The corresponding light intensity resonances in microspheres and coupling of two low-order linearly polarized modes in the fibers, LP₀₁ and LP₁₁, into the microspheres are observed. The LP₀₁ and LP₁₁ modes are delivered to the microsphere via a cylindrical optical fiber carrying light at two operating wavelengths, 1550 and 1300 nm correspondingly. The resonances behavioral differences generated by these fiber modes are also observed and explained. The properties of resonances generated by the LP₀₁ and LP₁₁ modes are analyzed using a linear polarizer inserted in the path of light propagating in optical fibers.


Capsaicin-induced substance P release and sensory control of vascular permeability in the guinea-pig ureter.
Substance P-immunoreactivity (SP-IR) in the guinea-pig ureter was found to be totally depleted after systemic capsaicin pretreatment. Removal of the inferior mesenteric ganglion (IMG) led to a total depletion of SP-IR from the rostral third of the ureter and to a partial depletion from the caudal third. Electrical stimulation of the IMG caused Evans blue extravasation mainly in the rostral third of both ureters, whereas stimulation of the right pelvic nerve caused Evans blue extravasation in the caudal third of the ureters on both sides. The responses to nerve stimulation were absent in capsaicin-pretreated animals. Furthermore, capsaicin caused release of SP-IR from ureter slices in vitro, this release was not inhibited by tetrodotoxin. Potassium (60 and 120 mM) also released SP-IR. It is concluded that SP-IR in the ureter is contained in capsaicin-sensitive sensory neurons reaching the ureter via both parasympathetic (caudal part) and sympathetic nerves (rostral part). Activation of these neurons by capsaicin leads to a peripheral release of SP-IR which most likely increases vascular permeability.


Alternated versus syncopated CHOP-PVB: two studies for the treatment of non-Hodgkin's lymphoma by the Southwest Oncology Group.
Based on a preliminary trial that suggested that CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone), and PVB (cisplatinum, vinblastine, bleomycin), are at least partially non-cross-resistant, the Southwest Oncology Group treated patients with unfavorable histology, non-Hodgkin's lymphoma with CHOP and PVB. In the first study, 76 eligible patients were given three courses of CHOP, with complete or partial responders receiving three courses of PVB followed by three further courses of CHOP. Nonresponders after the initial three cycles of CHOP, received six courses of PVB. In the second study, 154 eligible patients were treated with alternating cycles of the two drug regimens. The overall objective antitumor response (CR + PR) was 77% for the first study and 58% for the second. The complete remission rates were 48% and 38%, respectively. The overall survival for both studies is similar. These results are interpreted in terms of the Goldie-Coldman hypothesis.


Therapeutic Potential of Ranibizumab in Corneal Neovascularization.
Ranibizumab is a humanized, affinity-matured vascular endothelial growth factor (VEGF) antibody fragment that neutralizes all isoforms of VEGF and is FDA approved for use in ophthalmology. Recently it was suggested that ranibizumab may be useful in the treatment of corneal neovascularization, but in reality this therapy is not yet evidence based.


Impact of opioid therapy on gonadal hormones: focus on buprenorphine.
Objective The USA is in the midst of an opioid crisis. Understanding the impact of opioids and commonly used treatments for opioid dependence is essential for clinicians and researchers in order to educate and treat the nation's growing population with opioid use disorders. As a relatively new treatment for opioid dependence, buprenorphine is gaining popularity to the extent of becoming not only a preferred approach to the maintenance of opiate addiction, but also an option for chronic pain management. The purpose of this report is to review the available evidence on the endocrine effects of buprenorphine, particularly as it relates to the hypothalamic-pituitary-gonadal (HPG) axis, which is controversial and not fully defined. Method We conducted a Pubmed search (2000-2017) for human studies in the English language for articles that were available as full length regarding buprenorphine, endocrinopathy, hypogonadism, bone density, opioids. Case reports were also reviewed, although prospective studies and randomized controlled trials received more weight. Results Opioid induced hypogonadism is well established. Most studies report that buprenorphine being a partial agonist/antagonist may not be impacting the pituitary trophic hormones as much. There are reports of sexual dysfunction in subjects maintained on buprenorphine, some without hormonal correlation. Thus with the understanding that pertinent clinical studies are limited in number, varied in methodology, mostly cross sectional, predominantly in men and small number of participants, more research in this area is warranted. Conclusion Based on a comprehensive review of the available literature, we conclude that despite its increasing popularity, buprenorphine has not been adequately studied in respect to its long-term effects on the hypothalamic-pituitary-adrenal (HPA) axis. There is a great need for longitudinal systematic trials to define the potential buprenorphine-induced endocrine consequences.


Real-time projection MR angiography: feasibility study.
Intraarterial injections of small doses of gadopentetate dimeglumine were combined with a fast spoiled-gradient-echo magnetic resonance (MR) sequence to obtain real-time projection angiographic images of the rabbit aorta and canine coronary arteries. Arterial filling and washout, as well as venous and perfusion phases, were clearly displayed, demonstrating that arterial fluoroscopy in which an MR technique is used is feasible.


Origin of the Resistive Anisotropy in the Electronic Nematic Phase of BaFe(2)As(2) Revealed by Optical Spectroscopy.
We perform, as a function of uniaxial stress, an optical-reflectivity investigation of the representative "parent" ferropnictide BaFe(2)As(2) in a broad spectral range, across the tetragonal-to-orthorhombic phase transition and the onset of the long-range antiferromagnetic (AFM) order. The infrared response reveals that the dc transport anisotropy in the orthorhombic AFM state is determined by the interplay between the Drude spectral weight and the scattering rate, but that the dominant effect is clearly associated with the metallic spectral weight. In the paramagnetic tetragonal phase, though, the dc resistivity anisotropy of strained samples is almost exclusively due to stress-induced changes in the Drude weight rather than in the scattering rate, definitively establishing the anisotropy of the Fermi surface parameters as the primary effect driving the dc transport properties in the electronic nematic state.


Two alphapartitiviruses co-infecting a single isolate of the plant pathogenic fungus Rhizoctonia solani.
Seven dsRNA segments were detected from a single Rhizoctonia solani strain HG81. From the full-length cDNA sequences of four smaller dsRNA segments, the genomes of two related partitiviruses, designated as Rhizoctonia solani partitivirus 3 (RsPV3) and RsPV4, were determined. The genomes of RsPV3 and RsPV4 are both composed of two separate dsRNA segments, with each segment possessing a single open reading frame (ORF). ORF1 from RsPV3 and RsPV4 encodes a putative RNA-dependent RNA polymerase, while ORF2 of RsPV3 and RsPV4 encodes a putative capsid protein. RsPV3 and RsPV4 share high sequence identity with viruses classified within the genus Alphapartitivirus, family Partitiviridae.


Causes of mortality in drunkenness offenders followed-up for 2 years.
Causes of death in 8 of 235 drunkenness offenders each followed up for two years, have been described. The subjects followed up were a heterogenous population of alcohol abusers. The majority were alcohol dependent irregular heavy drinkers. The main causes of death were suicide, road traffic accident, domestic accident, liver cirrhosis, hypothermia (from exposure) and ischaemic heart disease. More than one cause of death was listed in all cases. Chronic alcoholism was frequently listed. Depression was another sub-ordinate cause of death. The overall observed rate of mortality was 30 times the expected rate which was many times higher than those reported by earlier workers for alcoholics generally. These findings were discussed and it was concluded that drunkenness offenders are a particular at risk sub group of alcoholics. In view of the appreciable post mortem blood alcohol levels, it was further concluded that chronic alcoholism and the actual state of being drunk were the two major causes of death in this group of alcohol abusers.


Ensuring the Quality of Evidence: Using the Best Design to Answer Health IT Questions.
The quality of logic in a research design determines the value of the results and our confidence regarding the validity of the findings. The purpose of this contribution is to review the principles of research design as they apply to research and evaluation in health IT. We review the architecture of research design, the definitions of cause, sources of bias and confounds, and the importance of measurement as related to the various types of health IT questions. The goal is to provide practitioners a roadmap for making decisions for their own specific study. The contribution is organized around the Threats to Validity taxonomy and explains how different design models address these threats through the use of blocking, factorial design, control groups and time series analysis. The contribution discusses randomized experiments, and includes regression discontinuity designs and various quasi-experimental designs with a special emphasis on how to improve pre/post designs. At the end, general recommendations are provided for improving weaker designs and general research procedures.


Nerve abscess in lepromatous leprosy. A case report and a discussion of pathogenesis.
An instance of nerve abscesses developing in a patient with lepromatous leprosy is reported. The pathogenesis of nerve abscess in lepromatous leprosy is briefly discussed. It appears that such abscesses may develop (i) from an ENL lesion in the nerve during ENL reaction, (ii) because of exacerbation of existing lepromatous lesion, (iii) arise as an "exacerbation nodule", (iv) due to quiet necrosis in a lepromatous granuloma, or (v) it may be iatrogenic.


Level of awareness of cervical and breast cancer risk factors and safe practices among college teachers of different states in india: do awareness programmes have an impact on adoption of safe practices?
Breast and cervical cancers are the most common causes of cancer mortality among women in India, but actually they are largely preventable diseases. Although early detection is the only way to reduce morbidity and mortality, there are limited data on breast and cervical cancer knowledge, safe practices and attitudes of teachers in India. The purpose of this study is to assess the level of awareness and impact of awareness programs in adoption of safe practices in prevention and early detection. This assessment was part of a pink chain campaign on cancer awareness. During cancer awareness events in 2011 at various women colleges in different parts in India, a pre-test related to cervical cancer and breast cancer was followed by an awareness program. Post-tests using the same questionnaire were conducted at the end of the interactive session, at 6 months and 1 year. A total of 156 out of 182 teachers participated in the study (overall response rate was 85.7 %). Mean age of the study population was 42.4 years (range- 28-59 yrs). There was a significant increase in level of knowledge regarding cervical and breast cancer at 6 months and this was sustained at 1 year. Adoption of breast self examination (BSE) was significantly more frequent in comparison to CBE, mammography and the Pap test. Magazines and newspapers were sources for knowledge regarding screening tests for breast cancer in more than 60% of teachers where as more than 75% were educated by doctors regarding the Pap test. Post awareness at 6 months and 1 year, there was a significant change in alcohol and smoking habits. Major reasons for not doing screening test were found to be ignorance (50%), lethargic attitude (44.8%) and lack of time (34.6%). Level of knowledge of breast cancer risk factors, symptoms and screening methods was high as compared to cervical cancer. There was a significant increase in level of knowledge regarding cervical and breast cancer at 6 months and this was sustained at 1 year. Adoption of BSE was significantly greater in comparison to CBE, mammography and the Pap test. To inculcate safe practices in lifestyle of people, awareness programmes such as pink chain campaign should be conducted more widely and frequently.


Rifampicin treatment of canine pyoderma due to multidrug-resistant meticillin-resistant staphylococci: a retrospective study of 32 cases.
Rifampicin has received increased interest in veterinary dermatology because of its activity against multidrug-resistant meticillin-resistant staphylococci (MRS). There is limited knowledge about the efficacy and safety of rifampicin in dogs. To provide information on response to treatment and adverse effects in dogs treated with rifampicin for multidrug-resistant MRS pyoderma. Thirty two dogs treated with rifampicin for rifampicin-susceptible multidrug-resistant MRS pyoderma. Retrospective review of medical records, including alanine aminotransferase (ALT) and alkaline phosphatase (ALP) serum activity levels and total bilirubin concentrations, obtained before and throughout the treatment, was performed. Oral rifampicin as sole systemic antimicrobial therapy (median dose 5 mg/kg twice daily) was effective in 71.88% of cases. Topical antimicrobials were used in most cases. Median duration of rifampicin treatment was five weeks for superficial pyoderma and four weeks for deep pyoderma. Gastrointestinal signs were reported in 15% of treated dogs. Statistically significant increases of ALT (P = 0.045) and ALP (P = 0.0002) values after 3-4 weeks of treatment was observed. The median increase was equal to 0.3 and ×1.5 the upper limit of the reference ranges for ALT and ALP, respectively. Oral rifampicin combined with topical antimicrobials can be considered an effective therapeutic option for canine superficial and deep pyoderma caused by rifampicin-susceptible multidrug-resistant MRS. Liver enzyme induction might be the most important cause of ALT and ALP increase associated with rifampicin therapy in dogs.


Endocrinological and histological changes induced by continuous low dose gamma-irradiation of the rat testis.
Young adult Sprague-Dawley rats were continuously whole-body irradiated with gamma rays at a dose-rate of 7 cGy/day for 92 days. Plasma LH, FSH and testosterone concentrations and testicular histology were quantified at different times during exposure. Irradiation selectively decreased spermatogonial numbers until 17 days of irradiation, following which a maturation depletion was observed. By the end of the exposure all germ cell types were reduced in number to about 10% of the control values. No significant changes were found in testosterone concentration nor in the weights of testosterone dependent accessory sex organs, LH plasma concentration increased slightly but not significantly at the end of irradiation. A significant increase in plasma FSH concentration occurred after the numbers of a spermatogonia and preleptotene spermatocytes had been reduced, when number of stage VII pachytene spermatocytes decreased to 36% of control values, whereas numbers of round spermatids and Sertoli cells were respectively 86% and 100% of the control values. These results suggest a possible role of pachytene spermatocytes in the regulation of inhibin production by the testis.


Optimizing chaos-based signals for complex radar targets.
There has been interest in the use of chaotic signals for radar, but most researchers consider only a few chaotic systems and how these signals perform for the detection of point targets. The range of possible chaotic signals is far greater than what most of these researchers consider, so to demonstrate this, I use a chaotic map whose parameters may be adjusted by a numerical optimization routine, producing different chaotic signals that are modulated onto a carrier and optimized for different situations. It is also suggested that any advantage for these chaos-based signals may come in the detection of complex targets, not point targets, and I compare the performance of chaos-based signals to a standard radar signal, the linear frequency modulated chirp. I find that I can optimize a chaos-based signal to increase the cross-correlation with the reflection from one complex target compared to the cross-correlation with the reflection from a different target, thus allowing the identification of a complex target. I am also able to increase the cross-correlation of the reflection from a complex target compared with the cross-correlation with the reflection from spatially extended clutter. I show that a larger output signal-to-noise ratio is possible if I cross-correlate with a reference signal that is different from the transmitted signal, and I justify my results by showing how the ambiguity diagram for a chaos-based signal can be different than the ambiguity diagram for a noise signal.


Effects of perioperative blood transfusion on the prognosis in hereditary and sporadic colon cancer.
We investigated the effects of perioperative blood transfusion in the prognosis of hereditary and sporadic colon cancer. There are 1075 colon cancer patients, including 936 sporadic colon cancer and 139 with hereditary colon cancer undergoing surgery at our hospital. All patients underwent 10 years of follow-up. In the sporadic group, mortality, local recurrence rate and distant metastases rate of transfused patients were significantly higher than non-transfused patients. The 10-year survival rates were significantly lower in patients receiving blood transfusions compared to non-transfused patients. In the hereditary group, mortality was higher in transfused patients compared to non-transfused patients.


Multiple receptor activation elicits synergistic IP formation in nonpigmented ciliary body epithelial cells.
We have examined the interaction between muscarinic and alpha(2)-adrenergic receptor activation on inositol phosphate (IP) formation in the nonpigmented cells of the ciliary body epithelium (NPE cells) of the rabbit. We have compared these changes with those previously observed in the intracellular free Ca(2+) concentration. Whereas muscarinic receptor activation causes an increase in intracellular Ca(2+) and IP formation, activation of alpha(2)-receptors does not significantly increase either intracellular Ca(2+) or IPs over basal levels. However, simultaneous activation of muscarinic and alpha(2)-adrenergic receptors with the specific agonists carbachol and UK-14304 produces massive Ca(2+) increases and results in a synergistic increase in IP formation. This synergistic IP formation is inhibited by both muscarinic and alpha(2)-adrenergic receptor antagonists as well as by pertussis toxin and an inhibitor of phospholipase C. IP formation is predominantly independent of intracellular Ca(2+), because it is decreased but not prevented by blocking the entry of Ca(2+) with LaCl(3) or chelating intracellular Ca(2+) with 1, 2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid. Thus synergistic IP formation underlies, at least in part, the synergistic increase in intracellular Ca(2+) resulting from simultaneous activation of muscarinic and alpha(2)-adrenergic receptors.


Solitary skin metastasis adjacent to ureterocutaneostomy 4 years after radical cystectomy for bladder cancer.
A 65-year-old Japanese woman underwent radical cystectomy and right nephroureterectomy for muscle-invasive bladder cancer. A left ureterocutaneostomy was constructed for urinary diversion. There was no evidence of recurrence for 4 years after the surgery. At 54 months after the surgery, however, she was referred with a chief complaint of painless skin erosion around the stoma. An incisional biopsy of the lesion showed no evidence of malignancy. Thereafter, the lesion was treated as a benign skin erosion. However, the erosion expanded over the next 4 months, and a second incisional biopsy revealed that the erosion was overlying malignant cells. Computed tomography showed a skin tumor of 4 cm in diameter. No other metastases were revealed on whole-body imaging examinations. Urine cytology was negative. A skin tumor extirpation was performed, and the specimen showed that the skin tumor consisted of malignant growth of papillary cells adjacent to the ureter, which were identical to those of the primary bladder cancer. A malignant component was not observed in the lumen of the resected ureter. No evidence of disease was observed in the first 3 months after extirpation. Reports of solitary skin metastasis from bladder cancer are rare, and only a few cases have been reported in the English literature. Because skin metastasis from bladder cancer can mimic a number of different benign conditions, a high index of suspicion may be necessary to make a definitive diagnosis.


Localization of monoclonal antibody G250 and bispecific monoclonal antibody CD3/G250 in human renal-cell carcinoma xenografts: relative effects of size and affinity.
A study was made of the relative effects of size and binding strength of various forms of the monoclonal antibody (MAb) G250, reacting with primary and metastatic human renal-cell carcinoma (RCC), on the localization in human RCC xenografts in nude mice. Preferential tumor localization was demonstrated after injection of 125I-labelled intact IgG, with increasing tumor/non-tumor ratios in time. Approximately 27.4% of the injected dose/gram (%ID/g) was localized in the xenograft 24 hr post-injection. A control MAb did not preferentially localize in xenografts. With F(ab')2 fragments, higher tumor/blood ratios were obtained, although a lower percentage of injected dose per gram was bound to the tumor, 24 and 48 hr post-injection. Using a bispecific MAb CD3/G250 F(ab')2 fragment, which reacts with CD3 on human T lymphocytes and binds monovalently to RCC, an enhanced accumulation in tumor tissue was also observed. The %ID/g tumor obtained with bispecific CD3/G250 F(ab')2 was comparable with %ID/g tumor found with G250 F(ab')2. The 10-fold lower binding affinity to RCC compared with intact IgG or F(ab')2 had only marginal effects on %ID/g tumor. These results show that MAb G250 preferentially localizes to RCC xenografts. Because injection of F(ab')2 fragments resulted in higher tumor/non-tumor ratios, G250 F(ab')2 may therefore be more suitable for diagnostic evaluation of RCC in patients. The tumor uptake is more dependent on size than on affinity. Furthermore, the data obtained with bispecific MAb CD3/G250 F(ab')2 support the hypothesis that this bispecific MAb may be able to target cytotoxic T lymphocytes to RCC in humans to mediate destruction of RCC.


Comprehensive analysis of the metabolomic characteristics on the health lesions induced by chronic arsenic exposure: A metabolomics study.
Early detection of the health lesions induced by chronic arsenic exposure (HLICAE) are crucial to prevent permanent arsenic-induced damage. If HLICAE can be identified in time, appropriate preventive and therapeutic measures may be provided without various avoidable lesions. The present study aims to assess the probability of HLICAE early recognition with metabolomics. Applying a case-control study, 94 participants with HLICAE (cases) and other 94 subjects without HLICAE (controls) were matched with gender and age (±1 year), coming from a previous chronic arsenic exposure cohort. Serum metabolomic profiles were assessed by ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) and analyzed with univariate and multivariate statistics. A total of 210 and 364 features were detected in positive and negative ion modes (ESI+/ESI-), respectively. The altered metabolic pathways included lipid and amino acid metabolisms. 28 metabolomics-based biomarkers were significantly associated with HLICAE and provided areas under the curve (AUC, 95% confidence interval) of 0.898 (0.836, 0.960) and 0.908 (0.855, 0.960) in the discovery phase, 78.6% and 86.4% of positive predictive values in the validation phase, in distinguishing HLICAE from controls in ESI+/ESI-, respectively. This study provides novel insights on mechanisms of health effects probably induced by chronic arsenic exposure, and these biomarkers may be applied in HLICAE early detection.


Impact of gender on neointimal hyperplasia following coronary artery stenting.
Whether gender affects long-term outcomes after bare metal stent implantation remains controversial. The aim of this study was to examine the impact of gender on neointimal hyperplasia in a large cohort of patients after stent implantation using 3-dimensional intravascular ultrasound. Lumen and stent areas were manually traced at 0.5-mm intervals throughout the stented segment. Using Simpson's method, lumen, stent, and neointimal (stent - lumen) volumes were calculated and standardized by stent length. Women were older, presented more often with hyperlipidemia or hypertension, and had smaller reference vessel diameter and mean stent area, compared with men. Although neointimal hyperplasia and neointimal thickness in women were similar to that in men, the percentage of neointimal hyperplasia (neointimal area divided by stent area) was higher in women due to the smaller stent area. After adjusting for stent area, the percentage of neointimal hyperplasia did not differ by gender. In conclusion, the results of this study indicate that neointimal hyperplasia after bare metal stent implantation in women is similar to that seen in men. Despite the similarity in outcome, there are several gender-specific differences in baseline characteristics.


Sensory evaluation of emissions from selected building products exposed to ozone.
The interaction of ozone with eight different building products was studied in test chambers. The products were plasterboard, two types of paints on plasterboard, two types of carpet, linoleum, pinewood, and melamine-covered particleboard. Four months of conditioning prior to the experiment had left the products with a low emission. The products' ability to remove ozone from the air covered a wide range. For three of the products (plasterboard with paint, carpet, and pinewood), it was shown that the removal was primarily due to interactions in the products' surfaces and only to a minor extent due to gas-phase reactions. Sensory evaluations were carried out for five of the products, with different ozone-removal potentials. A sensory panel assessed the emissions from sets of two specimens of each product; one specimen was exposed to a high, but realistic, ozone concentration (10 or 80 ppb) and one specimen was exposed to no ozone (background level < 3 ppb). The panel assessed odor intensity and was asked to choose which odor of the two specimens they preferred. The perceivable changes in emissions due to exposure of the products to ozone depended on the type of product. The greatest effect was seen for carpet. Carpet was the only product that showed significantly higher odor intensity when exposed to ozone. Besides, the effect of ozone on preference was strongest for carpet and resulted in a clear negative sensory evaluation. A similar but less pronounced effect was seen for pinewood and plasterboard with paint. No clear preference was seen for melamine and linoleum.


Respiratory Syncytial Virus in Otherwise Healthy Prematurely Born Infants: A Forgotten Majority.
Healthy, premature infants ≤35 weeks' gestational age (wGA) are universally recognized to be at an increased risk of perinatal morbidity and mortality. Serious respiratory syncytial virus (RSV) lower respiratory tract infection imposes an additional burden of illness on these infants following hospitalization. Incurred morbidities relative to term infants include longer lengths of hospital stay, admission to intensive care, and need for oxygen and mechanical ventilation, all of which are associated with increased hospital costs. The highest morbidities are experienced by premature infants who are youngest (<3 months' chronological age) and are of lower gestational age. Short- and long-term follow-up indicates that healthy preterm infants both of lower gestational age and who are late preterm have obstructive lung function at baseline, which is further compromised by RSV-related infection during infancy. There is increasing evidence that childhood exposure to an episode of RSV infection may set the stage for an abnormal respiratory function trajectory, which, in adulthood, leads to chronic obstructive pulmonary disease. Healthy premature infants <32 wGA merit RSV prophylaxis based on existing data, whereas moderate- and high-risk preterm infants 32 to 35 wGA should be selectively and cost-effectively targeted for prophylaxis using validated risk scoring tools and country-specific thresholds for funding.


Radiofrequency ablation for early-stage breast cancer: treatment outcomes and practical considerations.
Radiofrequency ablation (RFA) for early-stage breast cancer has the potential advantage of being a less invasive treatment associated with improved cosmetic outcome. The aim of this review was to summarise the reported treatment outcomes of ultrasound-guided RFA for early-stage breast cancer and to highlight practical considerations with regard to this treatment. A search of the English-language literature concerning RFA for breast cancer treatment was performed. RFA is a technique that can be safely applied in patients with early-stage breast cancer, which is restricted to cT1-T2N0 ductal carcinoma with radiologically defined borders without any signs of multifocality or multicentricity. However, before RFA can be adopted as local therapy for early-stage breast cancer, more research is needed to assess the post-treatment pathological complete response and margin status, the long-term oncologic outcome in comparison to current standard breast conserving therapy and the potential cosmetic superiority of percutaneous RFA. RFA appeared to be a feasible technique for the treatment of early-stage breast cancer, but considerable practical considerations form an obstacle to introduce RFA as a standard of care.


Identification of Fic-1 as an enzyme that inhibits bacterial DNA replication by AMPylating GyrB, promoting filament formation.
The morphology of bacterial cells is important for virulence, evasion of the host immune system, and coping with environmental stresses. The widely distributed Fic proteins (filamentation induced by cAMP) are annotated as proteins involved in cell division because of the presence of the HPFx[D/E]GN[G/K]R motif. We showed that the presence of Fic-1 from Pseudomonas fluorescens significantly reduced the yield of plasmid DNA when expressed in Escherichia coli or P. fluorescens. Fic-1 interacted with GyrB, a subunit of DNA gyrase, which is essential for bacterial DNA replication. Fic-1 catalyzed the AMPylation of GyrB at Tyr(109), a residue critical for binding ATP, and exhibited auto-AMPylation activity. Mutation of the Fic-1 auto-AMPylated site greatly reduced AMPylation activity toward itself and toward GyrB. Fic-1-dependent AMPylation of GyrB triggered the SOS response, indicative of DNA replication stress or DNA damage. Fic-1 also promoted the formation of elongated cells when the SOS response was blocked. We identified an α-inhibitor protein that we named anti-Fic-1 (AntF), encoded by a gene immediately upstream of Fic-1. AntF interacted with Fic-1, inhibited the AMPylation activity of Fic-1 for GyrB in vitro, and blocked Fic-1-mediated inhibition of DNA replication in bacteria, suggesting that Fic-1 and AntF comprise a toxin-antitoxin module. Our work establishes Fic-1 as an AMPylating enzyme that targets GyrB to inhibit DNA replication and may target other proteins to regulate bacterial morphology.


[Micronutrients intake and urinary tract tumors in Córdoba, Argentina].
Micronutrients content of habitually consumed foods comprise a causal network model of cancer, but the evaluation of their effect on this pathology represents a great challenge because of the interdependence in their usual consumption. Several studies reported that nutrients can modify the urinary tract tumors (UTT) risk, although such evidence is still limited. To identify associations between dietary vitamins A, E, B6, C, phosphorus, selenium and zinc intakes and the presence of UTT in Córdoba, Argentina, considering the multicollinearity caused by the interdependence of their consumption. A case control study was carried out including 129 cases with incident histopathologically confirmed UTT and 257 controls. A food frequency questionnaire previously validated was administrated to each subject. Dietary intakes of vitamins A, E, B6, C, phosphorus, selenium and zinc were the variables of interest, each showing high correlation with each other and thus, causing collinearity. So, multiple logistic regression models were adjusted and their adaptation to the presence of correlation, Ridge regression, to obtain the odds ratio (OR). The models included terms of sex, age, body mass index (BMI), socioeconomic status, occupational exposure to carcinogens, tobacco consumption and caloric intake as covariates. Vitamin E and vitamin B6 showed a slight protective effect (OR: 0.943, CI 95% 0.897-0.998 and OR: 0.730 CI 95% 0.457-1.167). Selenium was slightly promoter (OR: 1.012 CI 95% 1.001-1.023). When multicollinearity is considered in the model, it is possible to obtain more accurate estimates of the modulation that some micronutrients have on the risk of UTT more precisely.


Factors influencing the outcome of infectious bronchitis vaccination and challenge experiments.
The factors influencing the outcome of infectious bronchitis vaccination and challenge experiments regarding the respiratory and renal systems are reviewed. Advantages and disadvantages of the available techniques for measuring protection against an infectious bronchitis virus challenge are discussed, including the definition of protection itself. Suggestions are made regarding some ways in which progress towards standardization of a recognized protocol for performing experimental challenge studies can be made and areas where more work is needed are indicated.


Chemical shift imaging at 3 Tesla: effect of echo time on assessing bone marrow abnormalities.
Our purpose is to test the effect of varied in-phase (IP) and opposed-phase (OP) sequence order on characterizing marrow signal changes at 3T. The study was HIPAA compliant and IRB approved. Informed consent was waived. At 3T, IP and OP sequences were acquired in three patients with biopsy-proven osteosarcomas, using two methods: approach 1 (OP acquisition before IP acquisition) and approach 2 (OP after IP). Signal intensity (SI) measurements in 12 locations of biopsy-proven osteosarcoma and in six locations with normal bone marrow were performed independently by two experienced musculoskeletal radiologists. The signal intensity ratio (SIR) was measured within the marrow where there was T1 signal lower than skeletal muscle. A SIR < 20 % on the OP compared with IP imaging was considered positive for marrow replacement, while SIR > = 20 % was considered negative. Interobserver agreement was measured by the Lin concordance correlation coefficient (CCC). In 75 % (18/24) of locations within the biopsy-proven tumors, the SIR was >20 % (SI drop more than 20 % in OP compared to IP) using approach 2 and in 100 % (24/24) of the locations the SIR was <20 % (SI drop less than 20 % in OP compared to IP) using approach 1, indicating a high percentage of false-negative results by approach 2, and no false-negative results with approach 1. There was good agreement between observer measurement (CCC = 0.96). At 3T, the OP sequence should be acquired prior to the IP sequence, because susceptibility artifacts on a later-acquired OP sequence may lead to an erroneous interpretation of marrow signal abnormalities.


Osseointegration of sintered porous-surfaced and plasma spray-coated implants: An animal model study of early postimplantation healing response and mechanical stability.
The osseointegration and long-term success of bone-interfacing implants are dependent on mechanical stability of the implant relative to host bone during the early healing period. The geometric design of an implant surface may play an important role in affecting early implant stabilization, possibly by influencing tissue healing dynamics. In this study, we compared the early tissue healing response and resulting implant stability for two surface designs by characterizing the histological and mechanical properties of the healing tissue around Ti6Al4V sintered porous-surfaced and Ti plasma-sprayed implants. The implants were inserted transversely in rabbit femoral condyles and evaluated at 0, 4, 8, and 16 days postimplantation. At 4 and 8 days after implantation, the early healing tissue (fibrin and collagenous matrix) was more extensively integrated with the three-dimensional interconnected structure of the sintered porous surface than with the irregular geometry of the plasma-sprayed coating. In addition, histological examination indicated that initial matrix mineralization leading to osseointegration occurred more rapidly with the porous-surfaced implants. The more extensive tissue integration and more rapid matrix mineralization with the porous-surfaced implants were reflected in the mechanical test data, which demonstrated greater attachment strength and interfacial stiffness for the porous-surfaced implants 4 and 8 days postimplantation (p <.05). Sixteen days after implantation, both implant designs were osseointegrated and had comparable attachment characteristics. These data demonstrate that appropriate surface design selection can improve early implant stability and induce an accelerated healing response, thereby improving the potential for implant osseointegration.


Progression of acetabular periprosthetic osteolytic lesions measured with computed tomography.
A better understanding of the factors associated with the size and/or progression of osteolytic lesions has been hampered by a lack of sensitivity of radiographic measurement techniques. We retrospectively analyzed quantitative computed tomography scans that had been made with use of a high-resolution multi-slice scanner with a metal artifact-suppression protocol. The scans had been made to determine the volume of osteolytic lesions around thirty-five cementless Harris-Galante acetabular components that had been in situ for at least ten years. Repeat scans of thirty hips allowed for the measurement of progression in the size of osteolytic lesions over a one-year period. Associations between the volume of osteolytic lesions, progression in the size of the lesions, polyethylene wear since the time of implantation, change in component position, and patient-related variables (age, gender, body mass index, activity level, walking limitations, joint pain, and function) were determined. In sixteen of the thirty hips that had repeat computed tomography scans, the lesions progressed in size during the study period. The median size of the lesions in these sixteen hips was 10.3 cm(3) at the time of the initial scan, compared with 13.3 cm(3) at a median of fifteen months later (p = 0.001). Osteolytic lesions measuring >10 cm(3) in volume on the initial scan were 2.5 times (95% confidence interval 1.3 to 4.8 times) more likely to progress in size over one year than smaller lesions were. Patients with greater polyethylene wear rates, higher activity levels, no walking limitations, and larger prosthetic femoral head dimensions (26 or 28 mm) had significantly larger osteolytic lesions (p < 0.0001, p = 0.009, p = 0.006, and p = 0.028, respectively). Progression in the size of the osteolytic lesions over one year was significantly associated with larger initial osteolytic lesions (p = 0.002), greater polyethylene wear rates (p = 0.009), and larger (26 or 28-mm) prosthetic femoral head dimensions (p = 0.019). There is considerable variation in the rates of progression of the size of osteolytic lesions around stable acetabular components. Lesion size and the progression of lesion size are generally related to polyethylene wear rates, higher patient activity levels, and larger-diameter femoral heads. Osteolytic lesions measuring >10 cm(3) in volume are associated with a high rate of progression.


Influence of isoproterenol on myocardial energetics. Experimental and clinical investigations.
The influence of isoproterenol on myocardial performance and energetics was investigated in normal guinea pig myocardium and in patients with normal left ventricular function. The in vitro experiments were performed by simultaneous isometric force and heat measurements using sensitive antimony-bismuth thermopiles. Following the application of isoproterenol (10(-8) M) isometric peak twitch tension and tension-time integral increased significantly by 185% and 142%, respectively. Tension-independent heat which reflects high energy phosphate hydrolysis of excitation-contraction coupling increased by 183%. Tension-dependent heat reflecting the high energy phosphate hydrolysis of the crossbridges increased by 417%. The ratio of tension-dependent heat to tension-time integral increased by 131%. The recovery/initial heat ratio, reflecting the efficiency of the recovery metabolism, and the resting metabolism did not significantly change. In the patients the effect of isoproterenol on myocardial energetics was evaluated in terms of myocardial efficiency. Following isoproterenol administration, left ventricular systolic stress-time integral decreased by 49% due to reductions in end-diastolic pressure, end-diastolic volume and duration of systole. Pressure-volume work remained unchanged. Myocardial oxygen consumption per minute increased in proportion to heart rate. The ratio of myocardial oxygen consumption per beat to left ventricular systolic stress-time integral increased significantly by 95%. External myocardial efficiency was unaltered. Thus, isoproterenol increases the energy turnover of excitation-contraction coupling and increases the energy consumption of the crossbridges disproportionately to developed tension-time integral in the guinea pig heart.


Genomic instability en route to and from cancer stem cells.
Cancer is caused by successive gene mutations that amount to confer malignant phenotype. Genomic instability (GIN) is considered a key endogenous mechanism for accumulation of mutations, and therefore, has been proposed as an engine of tumorigenesis. Recently, cancer stem cells, or tumor initiating cells, have been identified in a variety of human cancers. These cancer stem cells (CSCs) are believed to be responsible for the initiation of malignant growth and metastasis of some, and perhaps all cancer types. How are these two engines of tumorigenesis related to each other? Is GIN a driving force in the genesis of cancer stem cells? Is the genome in CSCs inherently unstable? Could GIN in CSCs be the cause of the observed cancer cell heterogeneity? In this article, we will discuss some early clues indicating that these two driving forces of tumorigenesis appear to be intimately connected.


Pulmonary adenocarcinoma complicated with pulmonary infarction presented as intrapulmonary metastases: a report of a case.
Pulmonary adenocarcinoma complicated with a pulmonary infarction presenting as an intrapulmonary metastasis is relatively rare. We present a case of pulmonary infarction manifesting as intrapulmonary metastases of lung cancer. A previously healthy 59-year-old woman was admitted to our hospital for evaluation of abnormal shadows in the right lower lung field. Laboratory tests showed no abnormalities except for a slight elevation of carcinoembryonic antigens (CEAs). Computed tomography (CT) of the chest revealed a hilar mass lesion with parenchymal lesions in the periphery of the right lower lobe, highly suspected to be a pulmonary adenocarcinoma with intrapulmonary metastases. A diagnosis of pulmonary adenocarcinoma was confirmed by a transbronchial brushing examination. A right middle and lower bilobectomy with mediastinal lymph node dissection was due to hilar lymphadenopathy and a lower lobe invasion of the main tumor. Histopathological findings of the resected specimens revealed poorly differentiated adenocarcinoma of the lung with N1 (number 11i and 12 l) disease and multiple pulmonary infarctions with coagulation necrosis and recanalization. Our case suggests that pulmonary infarction associated with lung cancer should be considered as one important cause of peripheral pulmonary nodules.


Proof of principle of helium-beam radiography using silicon pixel detectors for energy deposition measurement, identification, and tracking of single ions.
Hadron therapy has the capability to provide a high dose conformation to tumor regions. However, it requires an accurate target positioning. Thus, the precise monitoring of the patient's anatomical positioning during treatment is desirable. For this purpose, hadron-beam radiography with protons (pRad) and ions (iRad) could be an attractive tool complementing the conventional imaging technologies. On the pathway to an envisaged clinical application, several challenges have to be addressed. Among them are achieving the desired spatial resolution in the presence of multiple Coulomb scattering (MCS), performing radiographs with a sufficient thickness resolution at clinically applicable dose levels, and the search for combinations of particularly suitable hadrons and detectors. These topics are investigated in this work for a detection system based on silicon pixel detectors. A method of iRad based on energy deposition measurements in thin layers is introduced. It exploits a detection system consisting of three parallel silicon pixel detectors, which also enables particle tracking and identification. Helium ions, which exhibit less pronounced MCS than protons, were chosen as imaging radiation. A PMMA phantom with a mean water-equivalent thickness (WET) of 192 mm, containing maximal WET-variations of ±6 mm, was imaged with a 173 MeV/u helium ion beam at the Heidelberg Ion-Beam Therapy Center. WET-differences in form of 2.3 mm × 2.3 mm steps were aimed to be visualized and resolved in images of the energy deposition measured behind the phantom. The detection system was placed downstream of the imaged object in order to detect single ions leaving it. The combination of the measured information on energy deposition, ion type, and the track behind the phantom was used for the image formation, employing a self-developed data-processing procedure. It was shown that helium-beam radiography is feasible with the reported detection system. The introduced data preprocessing purified the detector signal from detector artifacts and improved the image quality. Additionally, the rejection of hydrogen ions originating from nuclear interactions was shown to increase the contrast-to-noise ratio (CNR) by at least a factor of 2.5. This enabled the resolution of relative thickness differences of 1.2% at a dose level typical for diagnostic x-ray images. The spatial resolution was improved by taking into account the direction of single helium ions leaving the phantom. A spatial resolution (MTF10% ) of at least 1.15p mm-1 for the presented experimental set-up was achieved. A successful feasibility study of helium-beam radiography with the introduced detection system was conducted. The methodology of iRad was based on energy deposition measurements in thin silicon layers. The tracking of single ions and the method of the ion identification was shown to be important for helium-beam radiography in terms of spatial resolution and CNR.


Characterization of modified and normal deoxyoligonucleotides by MALDI, time-of-flight mass spectrometry.
A commercially available, matrix-assisted, laser desorption/ionization (MALDI), time-of-flight mass spectrometer has been used for the successful characterization of picomole quantities of modified deoxyoligonucleotides. The procedure was found to be applicable to the analysis of a variety of modified synthetic structures that included oligos with an intact dimethoxytrityl-blocking group, with omega-aminohexyl- and omega-hexyl-modified bases and with alterations to the normal phosphate backbone: 2'-5' and phosphorothioate linkages. Use of an alpha-cyano-4-hydroxycinnamic acid/ammonium formate based matrix gave sharp peaks, sensitivity to 1 pmol, accuracy to 0.06% on average and avoided the necessity for cryogenic technique and/or specialized equipment. Mixtures of normal and modified oligonucleotides worked well without any special precautions as long as the modified oligonucleotides contained a polyanionic backbone. Modified oligonucleotides that contained an amide linkage in place of the usual phosphate ester link required a sinapinic acid- or esculetin-based matrix with no ammonium formate. Crude oligonucleotides could be rapidly analyzed as a quality-control measure using from 10 to 20 pmol of a typical 0.2-mumol scale synthesis.


CT imaging of angiogenesis.
Tumor angiogenesis has significant implications in the diagnosis and treatment of various solid tumors. With the advent of fast, multi-slice CT scanners, CT imaging techniques capable of qualitative and quantitative analysis of tumor angiogenesis have been the subject of extensive investigation in the past 2 decades. The fundamental bases for CT imaging of angiogenesis are both the transport by blood flow of intravenously administered iodinated contrast material to tissue and the exchange by diffusion of these contrast molecules between the intravascular space and the extravascular interstitial space. With current fast CT scanners both tissue and vascular enhancement can be measured and traced over time at small time intervals to allow detailed modeling of the distribution of contrast agent in tissue. Both compartmental and distributed parameter models for contrast transport and exchange have been developed to quantify from the CT data the following angiogenesis related parameters: tissue blood flow, blood volume, mean transit time, contrast arrival time, capillary permeability surface area product and hepatic arterial fraction in case of the liver. This review addresses the following aspects of CT imaging of angiogenesis: 1) basic concepts related to the understanding of both compartmental and distributed parameter models; 2) comparison between both types of models; 3) practical issues with respect to the measurement of the arterial input function, which is required for the solution of both types of models; and, 4) illustration of the application of a distributed parameter model, the Johnson and Wilson model, in a number of experimental studies.


Is it safe and useful, laparoscopic peritoneal lavage in the treatment of acute diverticulitis of octogenarian patients? A multicenter retroprospective observational study.
Diverticular disease of the colon also affects older people. Generally, older patients with diverticulitis may be regarded as too risky to undergo surgery. This retroprospective multicentric observational study aims to assess the safety and benefits of laparoscopic peritoneal lavage (LPL) in elderly patients with perforated sigmoid diverticulitis. We hospitalized in urgency 100 patients, aged over 75, for sigmoid diverticulitis. Sixty-nine patients were treated with conservative medical therapy, while 31 were treated surgically, in which the surgery was performed in urgency in 18 cases, while in election in 13 cases. Laparoscopic peritoneal lavage was made in urgency in five cases. The mean age of the sample was 81.72. Thirty-one patients underwent surgery, and five patients were treated in urgency with laparoscopic peritoneal lavage. Perioperative mortality was zero. None of the patients who underwent laparoscopic peritoneal lavage showed recurrent disease. Diagnostic laparoscopy can be useful in elderly patient, since these patients may benefit from a more conservative surgical strategy. The selection of patients to be subjected to laparoscopic lavage must be very rigorous.


Determination of a unique and immunodominant epitope of human T cell lymphotropic virus type I.
The identification and isolation of unique and immunogenic recombinant epitopes for human T cell lymphotrophic virus (HTLV) type I might allow the development of an antibody-based assay to differentiate between HTLV-I and HTLV-II infections. To test the feasibility of this approach, an HTLV-I envelope epitope was isolated by immunoscreening of a lambda gt11 recombinant HTLV-I DNA library with a human monoclonal antibody to HTLV-I. This recombinant epitope. MTA-4, when tested with sera from HTLV-I- or HTLV-II-infected individuals, was reactive with all HTLV-I and nonreactive with all HTLV-II antisera. These results indicate that MTA-4 is a unique and immunodominant epitope on HTLV-I and confirm the usefulness of human-derived monoclonal antibodies in an experimental approach to dissect the human humoral response to a viral pathogen.


Surgical management of congenital vascular rings.
Case histories of 53 patients with surgically treated vascular rings are presented. The diagnosis was strongly suggested in all patients by symptoms of tracheosophageal obstruction and was confirmed by barium esophagogram, which showed typical bilateral and posterior indentations in the esophagus. Angiography was rarely used although it is helpful in doubtful cases. Endoscopic studies were considered unnecessary and potentially harmful. A left posterolateral thoractomy afforded ample access for division of the ring in all patients. Two patients died who were operated upon during the early experience. There were no postoperative deaths among the last 45 consecutive patients. All survivors had excellent symptomatic relief although complete resolution of symptoms took several months in some patients. All survivors had excellent symptomatic relief although complete resolution of symptoms took several months in some patients. The importance of early diagnosis and prompt surgical division is emphasized.


Use of bone marrow stromal cells for tendon graft-to-bone healing: histological and immunohistochemical studies in a rabbit model.
Despite increasing attention on the issue of tendon-to-bone integration, there has been no animal study on the use of cell therapy for promoting the insertion healing of tendon to bone. To determine the efficacy of using a large number of bone marrow stromal cells (bMSCs) to enhance tendon-to-bone healing. Controlled laboratory study. The hallucis longus tendons were translated into 2.5-mm diameter calcaneal bone tunnels in a New Zealand white rabbit model. The bone tunnels were treated with or without bMSCs. Three specimens from each group were harvested at 2, 4, and 6 weeks postoperatively and evaluated by conventional histological and immunohistochemical methods. At 4 weeks, the specimens with bMSCs exhibited more perpendicular collagen fiber formation and increased proliferation of cartilage-like cells, which was indicated by positive collagen type-II immuno-staining of the tendon-bone interface. In contrast, the specimens without bMSCs demonstrated progressive maturation and reorganization of fibrous tissue aligned along the load axis. Introduction of a large number of bone marrow stromal cells to the bone tunnel have shown to improve the insertion healing of tendon to bone in a rabbit model through formation of fibrocartilagenous attachment at early time points.


[Etiology and clinic of status epilepticus].
In the presented study we examined 110 patients who suffered from status epilepticus. Total 148 status were analysed with regard to etiology, releasing factors, course and treatment. Causes stressed were head injury with brain damage and intracranial space occupying, especially in the frontal region. Head injury with opened dura mater showed more tendency for development of status than closed ones. In a quarter of all cases origin couldn't be found. All these, with exception of one case, developed intercurrently. Isolated or initial always was consequence of brain lesion, the origin of which was or has been detected. No trend with reference to distribution of age in the particular forms of status were found out. In a third part of all a releasing factor could be discovered. Most the question in these cases was failure in medicamental treatment. We couldn't draw one's interferences about pathogenesis from etiology, age of patient, place in course and form of status. About in a quarter of all status we found defective neurological sequels, in 12% also psychical disturbances. 16 patients died during the period of observation, but only 2 within 24 hours, all together 8 in the first 14 days in deap coma. Immediately cause of death were above all complications of the heart, circulation of blood and respiration tract. In the most cases the treatment consisted in a mixture of anticonvulsive medicaments. The predominant rate of status epilepticus could be inhibited within 24 hours, only 20 lasted a longer time.


Comparison of the clinical signs, pathological and immuohistochemical findings in visceral organs of chickens experimentally infected with Salmonella Zega through three routes.
Salmonella Zega isolated from natural outbreaks that were characterized by high mortality in poultry farms in three Southwestern States of Nigeria was used to inoculate two week-old chicks through different routes in order to determine and compare the clinical signs, pathological and immunohistochemical changes in each route of infection. The birds were divided into 4 groups of 25 each as groups A (orally inoculated), B (intraperitoneally inoculated), C (inoculated per cloaca) and D (uninoculated control). All the birds were inoculated with 0.2 ml of 1 × 108 cfu of the bacteria. Clinical signs were observed and recorded according to the route of infection, and with the days post-infection from day 0 till day 10 post-infection. Two birds from each group were sacrificed every 24 h and examined for gross lesions, which were described and scored according to the route of infection and days post-infection. Samples of visceral organs were collected for bacteriology, histopathology and immunohistochemistry. Clinical signs in chicks infected orally and intraperitoneally were weakness, anoraexia lethargy, somnolescence, yellowish diarrhoea observed from 4 days till day 10 post infections. Mild sign of weakness was observed in chickes infected per cloaca, from day 3 to 7. The gross lesions were congestion, oedema and enlargement and necrosis in visceral organs from day 4 to 10 post infection in orally and intraperitoneally infected chicks, but mild vascular changes were observed in chicks infected per cloaca, except in the caecum were lesions of necrosis and infiltration of inflammatory cells were moderate to severe. Microscopic lesions were necrosis of host cells and infiltration by lymphocytes, heterophils and macrophages in multiple organs observed from day 4 to 10 post infection in orally and intraperitoneally infected chicks. Immunoreactions were observed in all the visceral organs examined. Clinical signs, pathological and immunohistochemical findings were mild in chicks infected per cloaca, except caecal lesions. Salmonella Zega isolated from an outbreak in poultry farms in Abeokuta, Nigeria was highly pathogenic in chicken and produced similar findings in oral and intraperitoneal infections; while per cloacal infection showed a localized infection of the caecum.


Adalimumab as steroid-sparing treatment of inflammatory-stage thyroid eye disease.
Steroids are often used as medical therapy for active thyroid eye disease (TED). While high-dose steroids have been shown to be effective in reducing the severity of TED symptoms, the side effects of steroids can be severe. As the pathogenesis of TED is thought to involve the upregulation of proinflammatory cytokines, including tumor necrosis factor-α (TNF-α), it has been postulated that anti-TNF agents may be used as steroid-sparing agents in the treatment of TED. This retrospective study was conducted to examine the efficacy of adalimumab, a subcutaneously administered TNF-α antagonist, in treating the inflammatory symptoms of active TED. All patients in the inflammatory phase of TED who were treated with adalimumab at the Jules Stein Eye Institute over a 2-year period were reviewed. Data concerning visual acuity, optic nerve function, extraocular motility restriction, binocular visual fields, and proptosis were extracted from patient charts. Clinical photographs from baseline and 3-month follow-up visits were reviewed by masked orbital specialists. Each photograph was graded on the severity of conjunctival injection, chemosis, eyelid erythema, and eyelid edema on a scale from 1 to 4. An inflammatory score was calculated as the sum of these 4 elements. Groups were compared using paired t tests. Six of 10 patients showed a decrease in inflammatory score while on adalimumab, whereas 3 showed an increase and 1 stayed the same. One patient experienced a significant complication (hospital admission for sepsis). Eight patients received concomitant tapering steroids during the first 6 weeks of therapy as the adalimumab reached maximum efficacy. When data from all 10 subjects were analyzed together, there was no significant change in inflammatory index after 3 months of treatment with adalimumab. However, when the 5 patients with a high baseline inflammatory index (>4) were considered separately, there was a significant improvement (mean decrease of 5.2±2.7; p<0.01) after adalimumab treatment. Four of 5 patients also reported a subjective improvement in symptoms while on adalimumab. This study suggests that adalimumab may have a role in the treatment of active TED with prominent inflammatory symptoms. The use of adalimumab and other immunosuppressive agents in the treatment of TED may help to mitigate some of the metabolic and psychiatric side effects of pulsed steroid treatment. A future randomized controlled study will be necessary to determine the efficacy of adalimumab as a primary therapy for TED.


PREDICTORS OF SELF-REPORTED GAINS IN A RELATIONSHIP-BASED HOME-VISITING PROJECT FOR MOTHERS AFTER CHILDBIRTH.
We assessed mothers' self-reported gains from a postpartum home-visiting (HV) project in which home visitors are volunteer mothers from the community. Hypotheses were that gains are positively related to (a) mothers' felt-closeness with their home visitor, (b) mothers' level of sociodemographic risk, and (c) the home visitors' preproject training in support services for families or children (Professionalism). One hundred sixty-four clients returned written evaluations of the HV project. Items assessing gains were reduced to two factors: Improved Well-Being ("Self") and Improved Infant Care ("Infant"). Repeated measures general linear models, with Gains (Self, Infant) as the repeated measure, and multiple regression analyses evaluated the hypotheses. Across the sample, gains on both factors were moderate, although gain scores were higher regarding Self than for Infant. Results show that (a) Mothers' felt-closeness with their volunteer was strongly related to mothers' gains; (b) high-risk mothers gained more from the project than did mothers of lower risk, particularly regarding Infant Care; and (c) mothers visited by volunteers who were professionals reported more substantial gains than did mothers visited by volunteers who were not professionals. Findings can help explain variance in mothers' gains from such projects and could be useful in improving their efficacy.


[Lower limb stump reconstruction with a functional calcaneo-plantar unit free flap. A series of 16 cases].
The main objective of surgery, once amputation is inevitable, is to preserve a functional stump. This report describes the immediate reconstruction of 16 leg stumps in children by transfer of a functional calcaneo-plantar unit. Of these, 3 were thigh and 13 were lower leg reconstructions. Amputation was performed for tumor in 4 cases, and was due to accidents in the remaining twelve. The main technical features of flap preparation are preservation of the calcaneum branch and attachment of the heel skin to the greater tuberosity of the calcaneum. One case resulted in failure due to vascular thrombosis. The other 15 cases resulted in bone consolidation after an average of 45 days, sensitive protection by 70 days, and very good trophic and protective results. The provision of good distal pressure area encourages overall development of the child. There was no morbidity at the donor site, and because there is no major muscle mass in the distal fragment, the overall risk is very low compared to that of total proximal leg replantation. The transfer of functional calcaneo-plantar tissue as a single unit is the best strategy for one-step restoration of good distal support area for the stump. All surgeons liable to perform leg amputations should be aware of this technical approach.


Synthesis of novel chalcogenide 'lifebelts' and their electrogenerated chemiluminescence.
Novel chalcogenide lifebelts have been prepared by using a simple sacrificial template method, and their electrogenerated chemiluminescence properties were studied.


Robotic single docking total colectomy for ulcerative colitis: First experience with a novel technique.
We describe a novel technique that could aid the surgeon to perform a total proctocolectomy with a single docking position of the da Vinci Si HD System. Patients were positioned in 20° Trendelenburg lithotomy split legs position. A 12-mm trocar was for camera and 3 more trocars were placed: two robotics on left and right flanks and one laparoscopic in left iliac fossa. The robot was docked between the legs of the patients. Four proctocolectomies were performed. Mean operative time was 235 min (range 215-255); mean blood loss was 100 cc (range 50-200). Median post-operative stay was 6 days. Overall morbidity was 75%, whereas major complications occurred in 25%. Post-operative mortality was null. The robotic single docking approach to perform total proctocolectomy for ulcerative colitis is a time-saving technique respect to the multiple docking approach.


Acceptance of hearing protection aids in members of an instrumental and voice music band.
There are barriers to effective hearing protection among musicians. To investigate the acceptance of hearing protection aids in members of an instrumental and voice music band. A prospective study of 34 members of the Municipal Indaial Band. Sound pressure levels were measured during a rehearsal, indicating mean levels ranging from 96.4 dB(A) to 106.9 dB(A). Subjects answered questionnaires and underwent audiometry. They attended a lecture in which folders and hearing protection aids were provided; subjects were asked to try using the protectors for 3 months. At the end of the study period, 56.2% reported not liking hearing protection, while 43.7 % accepted such protection. The most common complaints were discomfort with sounds (58.8 %) and tinnitus (47%). 77.1% said that music might cause hearing impairment. A statistically significant difference was observed in the right ear at 4 and 6 kHz and at the left ear in 3, 4 and 6 kHz when median thresholds were compared with those from unexposed controls. Although most subjects seemed aware of the risk, few took preventive measures against hearing loss. This suggests the need for periodic educational campaigns and specific legislation tailored to music professionals.


A neural network model for visual selection and shifting.
In this paper, a two-layer network is built to simulate the mechanism of visual selection and shifting based on the mapping dynamic model for instantaneous frequency. Unlike the differential equation model using limit cycle to simulate neuron oscillation, we build an instantaneous frequency mapping dynamic model to describe the change of the neuron frequency to avoid the difficulty of generating limit cycle. The activity of the neuron is rebuilt based on the instantaneous frequency and in this work, we use the first layer of neurons to implement image segmentation and the second layer of neurons to act as visual selector. The frequency of the second neuron (central neuron) is always changing, while central neuron resonates with the neurons corresponding to an object, the object is selected, then with the central neuron frequency changing, the selected object loses attention, the process goes on.


System of Scientific Advisory Boards at the National Cancer Institute.
This article describes the Boards of Scientific Counselors of the National Cancer Institute (NCI) and focuses on their role and their relationship to the other advisory boards used by NCI in the governance of the National Cancer Program. The advisory boards consist of the President's Cancer Panel, the National Cancer Advisory Board, the Boards of Scientific Counselors of the four programmatic divisions, and the Frederick Cancer Research Facility Advisory Committee. Each of these boards is an element of the organized system by which NCI obtains its scientific advice. The system provides a forum in which scientific directions and priorities are debated, ideas for research initiatives compete, and advice is given on the allocation of research and training funds. This article is a sequel to a number of earlier papers reviewing the corporate management structure that has been developed over the past decade at NCI.


Association between fetal interleukin-1 receptor antagonist gene polymorphism and unexplained fetal death.
In spite of extensive clinical examinations or autopsies, as many as 15% to 40% of stillbirths remain unexplained. A systemic fetal inflammatory response is an independent risk factor for severe neonatal morbidity, mediated by proinflammatory cytokines. As a major anti-inflammatory cytokine, interleukin-1 receptor antagonist (IL-1ra) plays a crucial role modulating the proinflammatory response. The gene coding for IL-1ra (IL1RN) is polymorphic. We hypothesized that fetal possession of a specific allele, IL-1RN*2, associated with increased proinflammatory responses, may increase susceptibility to intrauterine fetal death. Fetal kidney cells were obtained from paraffin blocks of 27 unexplained stillbirths. DNA was isolated and tested for IL-1RN genotypes by polymerase chain reaction. As a control group, DNA from 302 live births was also tested. There was an enhanced rate of IL-1RN*2 homozygocity, 41%, among unexplained stillbirths compared with the control group, 8.6% (P < .001). Histologic analysis of fetal tissues demonstrated a predominant proinflammatory response in IL-1RN*2 homozygote fetuses. Extensive screening (microbiology, maternal serology, placenta histology) did not identify any specific trigger agent. There is an association between unexplained stillbirth and fetal homozygous IL1RN*2 carriage.


Mosaic Drosophila wings reveal regional heterogeneity in the guidance of ectopic axons.
In most studies of axon guidance in the peripheral tissues of insects, the ability of experimentally perturbed axons to pathfind was examined only along their normal pathways. This means that regions normally devoid of axons have not been sampled for their ability to influence axonal trajectories. To examine this question, we have induced the formation of single sensory neurons in a variety of abnormal locations in the developing wing of Drosophila and have examined the course taken by their axons. The axons of such ectopic neurons have a regionally varying tendency to grow in the normal, proximal direction. This proximal bias approaches 100% for neurons located in the distal part of vein L2 and 70% in distal vein L4 but falls to chance (50%) along vein L5. Thus, neurons forming in ectopic regions of the wing, especially those found near the normal axon pathways (veins L1 and L3), have a high probability of growing axons in the correct direction. We conclude that information relevant to axon outgrowth is not restricted to the normal pathways. Whether this information is intrinsic or extrinsic to the neurons, and why its strength shows such conspicuous regional variation, awaits further study.


Patchy ischemic retinal whitening in acute central retinal vein occlusion.
To describe a new fundus abnormality in nonischemic central retinal vein occlusion and its pathophysiologic basis. Retrospective, observational case series. Eleven consecutive patients from a community-based retina referral practice who had central retinal vein occlusion (CRVO) and patchy ischemic retinal whitening (PIRW) and 225 consecutive patients from the same practice with CRVO and no PIRW. Patchy ischemic retinal whitening occurs in younger patients with nonischemic CRVO (P < 0.0003) and is associated with better visual outcomes than without PIRW (P = 0.0201). Patchy ischemic retinal whitening has a perivenular distribution in the macula, has no fluorescein angiographic correlate in milder cases, can occur before any retinal hemorrhages or macular edema, and resolves in 2 to 4 weeks. Cilioretinal arteriolar insufficiency is a common finding associated with PIRW (5/11 cases). The laboratory evaluation of patients with PIRW is generally normal. Patchy ischemic retinal whitening is a useful fundus sign of nonischemic CRVO that can precede other signs. Familiarity with this sign and its correlates will allow accurate diagnosis and counseling of affected patients.


A mitochondrial porin cDNA predicts the existence of multiple human porins.
Pores formed in the outer membrane of mitochondria by mitochondrial porin make it permeable to water-soluble metabolites smaller than approximately 5 kDa. We have isolated a full-length cDNA encoding a human porin. This probe detects a single approximately 1.5-kilobase mRNA species on Northern blots, but multiple hybridizing bands on genomic Southern blots. The open reading frame predicts a 38.1-kDa protein with a pI of 6.59 that is homologous but not identical to a previously reported protein sequence of a 31-kDa porin isolated from human lymphocytes (porin 31HL). The most striking difference between the two porins is that the sequence predicted by the cDNA is longer than the 31HL porin by 27 amino acids at the amino terminus and 38 amino acids at the carboxyl terminus. The porin cDNA directs the in vitro translation of two protein species of approximately 32 and approximately 36 kDa, which appear to result from alternate usage of AUG initiation codons. The 32-kDa protein is the predominant species imported into both rat and yeast mitochondria in vitro. Taken together, these results suggest that multiple porin proteins can be expressed in humans. Additionally, a porin consensus protein sequence has been identified that is conserved in eukaryotic organisms as diverse as yeast and man.


A Delphi-based consensus study into planning for biological incidents.
Biological incidents present a significant threat to health services in the UK. The objective of this study was to achieve consensus in all phases of biological incident planning and response. A three-round Delphi study was conducted using a panel of 23 experts from specialities involved in the management of biological incidents. The consensus and non-consensus outcomes from the Delphi study were subsequently presented for discussion in four syndicate groups at a one-day consensus conference funded by the Health Protection Agency. The results of each syndicate group discussion were presented at a subsequent plenary session at the end of the conference. Further iteration of both the consensus and the non-consensus outcomes of the Delphi study resulted in the endorsement, modification, integration or rejection of individual statements. 125 consensus statements were produced. The 125 synopsis consensus statements that all phases of biological incident planning and response. These can be used to inform policy decisions and translated into practical guidance for emergency planners and first responders at local, regional and national levels.


Aesthetic and oncologic outcomes after one-stage immediate breast reconstruction using a permanent biodimensional expandable implant.
Immediate breast reconstruction (IBR) with implants is the commonest method of reconstructive surgery after mastectomy. With careful patient selection, a stable implant pocket can be created at the primary operation to decrease the likelihood of further surgery to adjust the reconstructed side. One-stage IBR is cost effective but failed procedures requiring early revision may be costly as permanent expanders are expensive. Data were prospectively collected on all women undergoing a planned one-stage immediate breast reconstruction between 1997 and 2010. All patients had a Style 150 implant (Allergan, Marlow, UK). Descriptive statistics, Kaplan-Meier plots and, where applicable, Cox Proportional Hazards Regression was used to compare outcomes between groups. 249 planned one-stage IBRs were performed in 193 women, median age 45 years (range 20-77) with median follow-up of 101 months (range 27-159 months). 18/193 (9%) patients required implant exchange at 12 months and 66% of patients maintained their original implants at the time of census. Implant assisted latissimus appears to be robust even when radiotherapy was delivered. Disease free survival and breast cancer mortality were as expected for the breast cancer stage treated. With careful patient selection, one-stage implant IBR using a definitive anatomical expandable implant provides good long term reconstruction and safe oncologic outcome. Direct to implant decision algorithms may be influenced by future developments in acellular dermal matrix technology, but the ability to create a single-stage stable implant pocket with good surgical technique should not be forgotten.


Role of MHC class-I antigens and the CD3 complex in the lysis of autologous human tumours by T-cell clones.
Peripheral blood lymphocytes (PBL) of 4 patients with malignant effusions were stimulated for 6 days with purified autologous tumour cells, before isolation of the lymphoblasts and cloning by limiting dilution in interleukin-2 (IL-2). Forty-five clones were analyzed for cytotoxicity (CTX) against autologous, allogeneic tumour and erythromyeloid K562 cells of known status with respect to expression of major histocompatibility complex (MHC) antigens, estimated by reaction with the W6/32 (anti HLA, -A, -B, -C monomorphic) and TDR 31.1 (anti HLA-DR) monoclonal antibodies (MAb). All 45 clones were CD3+. Twenty-five (56%) of them were cytotoxic for at least one target; 24 were autoreactive (restricted in 7); 17 were alloreactive; 16 were K562 reactive. Under comparable conditions autoreactivity was partially blocked by W6/32 in 12/20 effector:target combinations; alloreactivity in 8/13 and K562 reactivity in 0/14. Modulation of effector cell surface CD3 antigens by OKT3 monitored by flow cytometry reduced autoreactivity in 9/14 combinations, alloreactivity in 2/6 and K562 reactivity in 0/4. W6/32 blocking and T3 modulation of cytotoxicity were almost invariably concordant against the same target. The data suggest that, to accomplish lysis of autologous and allogeneic tumour targets, certain clones require MHC recognition and a functional CD3 complex, while for others with similar target cell repertoires, there is no such requirement. It is possible that T-cell clones responding to a tumour-associated antigen (TAA) in the context of self MHC antigens can also respond to an allogeneic class-I product in the absence of TAA, and/or that aberrant class-I antigen expression on autologous tumours accounts for the alloreactivity.


Attentional processing of other's facial display of pain: an eye tracking study.
The present study investigated the role of observer pain catastrophizing and personal pain experience as possible moderators of attention to varying levels of facial pain expression in others. Eye movements were recorded as a direct and continuous index of attention allocation in a sample of 35 undergraduate students while viewing slides presenting picture pairs consisting of a neutral face combined with either a low, moderate, or high expressive pain face. Initial orienting of attention was measured as latency and duration of first fixation to 1 of 2 target images (i.e., neutral face vs pain face). Attentional maintenance was measured by gaze duration. With respect to initial orienting to pain, findings indicated that participants reporting low catastrophizing directed their attention more quickly to pain faces than to neutral faces, with fixation becoming increasingly faster with increasing levels of facial pain expression. In comparison, participants reporting high levels of catastrophizing showed decreased tendency to initially orient to pain faces, fixating equally quickly on neutral and pain faces. Duration of the first fixation revealed no significant effects. With respect to attentional maintenance, participants reporting high catastrophizing and pain intensity demonstrated significantly longer gaze duration for all face types (neutral and pain expression), relative to low catastrophizing counterparts. Finally, independent of catastrophizing, higher reported pain intensity contributed to decreased attentional maintenance to pain faces vs neutral faces. Theoretical implications and further research directions are discussed.


Determination of trace elements in porcine brain by inductively coupled plasma-mass spectrometry, electrothermal atomic absorption spectrometry, and instrumental neutron activation analysis.
Methods have been developed for the analyses of trace metals in various areas of porcine brains, (temporal, parietal, frontal cortex, both right and left hemispheres). Determinations were carried out using inductively coupled plasma-mass spectrometry (ICP-MS) and electrothermal atomic absorption spectrometry (ETAAS). The elements investigated were Li, Mn, Cu, Zn, Cd, Hg, and Pb by ICP-MS and Cu, Cd, and Mn by ETAAS. For determination by ICP-MS, a method of standard additions calibration coupled with internal standards was used, and for ETAAS, standard additions calibrations were prepared. The accuracy of all methods was determined using NIST and IAEA certified reference material. A small number of pig brains were analyzed by instrumental neutron activation analysis for Cr, Co, Cs, Fe, Rb, Se, Sc, Sb, and Zn using the comparator method of analysis. Four separate NIST standard reference materials have been used to examine the validity of the comparator method.


"Blowing in the wind": a review of teenage smoking.
One quarter of all adults in the UK are regular smokers, the vast majority having started smoking in their teens. Teenage smoking, especially in females, continues to increase both as regards the numbers of cigarettes smoked and the numbers of teenagers who regularly smoke. The main factors influencing teenagers to smoke are peer pressure, family members who smoke and experimentation. Nicotine dependence can develop very quickly and in the UK little attention has been directed towards helping teenagers break the habit. In global terms the figures are frightening. Of the 1.25 billion smokers, 800 million live in developing countries. In the UK, government legislation, restrictions on advertising and educational programmes may improve the situation in the near future but there is still little recognition that smoking is responsible for 4 million deaths each year worldwide and insufficient attention has been paid to children and young families to try to prevent children and teenagers from smoking in the first place.


Isolation, structure and fatty acid synthesis inhibitory activities of platensimycin B1-B3 from Streptomyces platensis.
Platensimycins B(1)-B(3) are natural congeners of platensimycin with modest to significant changes in the benzoic acid portion of the molecule, leading to attenuation in the biological activities and thus confirming the significance of the free carboxylate for the potent activity.


Ambroise Paré (1510-1590) and His Innovative Work on the Treatment of War Injuries.
The purpose of this study is to summarize the innovations of Ambroise Paré (1510-1590) on the treatment of war wounds and improving amputation technique through ligature in arteries and veins. Ambroise Paré debunked the widely accepted idea that gun powder was poisonous for wounds. He also minimized the use of cautery of wounds by his dressing methods and the application of ligature during amputations. All these innovative rationales revolutionized the practice of war surgery during the Renaissance and paved the way for the introduction of modern surgery. Nevertheless, although his wound dressing innovations became widely accepted, the same did not happen with ligature and amputation; those techniques could become widely applicable if one could somehow control bleeding until the blood vessels had been tied. This became possible much later in the 18th century when Jean Louis Petit invented the first useful and efficient tourniquet.


Rat brain slices oxidize glucose at high rates: a (13)C NMR study.
Since glucose is the main cerebral substrate, we have characterized the metabolism of various (13)C glucose isotopomers in rat brain slices. For this, we have used our cellular metabolomic approach that combines enzymatic and carbon 13 NMR techniques with mathematical models of metabolic pathways. We identified the fate and the pathways of the conversion of glucose carbons into various products (pyruvate, lactate, alanine, aspartate, glutamate, GABA, glutamine and CO(2)) and determined absolute fluxes through pathways of glucose metabolism. After 60 min of incubation, lactate and CO(2) were the main end-products of the metabolism of glucose which was avidly metabolized by the slices. Lactate was also used at high rates by the slices and mainly converted into CO(2). High values of flux through pyruvate carboxylase, which were similar with glucose and lactate as substrate, were observed. The addition of glutamine, but not of acetate, stimulated pyruvate carboxylation, the conversion of glutamate into succinate and fluxes through succinate dehydrogenase, malic enzyme, glutamine synthetase and aspartate aminotransferase. It is concluded that, unlike brain cells in culture, and consistent with high fluxes through PDH and enzymes of the tricarboxylic acid cycle, rat brain slices oxidized both glucose and lactate at high rates.


Theoretical analysis of radioactivity profiles during fast axonal transport: effects of deposition and turnover.
In a preceding study [Blum, J.J., and Reed, M.C. (1985): Cell Motil. 5:507-527], factors responsible for the shape and velocity of the leading edge of the radiolabeled organelle profile were analyzed, but processes that might influence the shape of the plateau-like region behind the advancing wave were ignored. It is now shown that deposition of material from the fast transport system into membrane-associated structures, degradation of such deposited material and its return to the soma by the retrograde transport system, or leakage of radiolabeled material from the axon can account for the shape of the plateau. Furthermore, these processes are compatible with the maintenance of such structural inhomogeneities as the nodes of Ranvier.


[Bronchopulmonary cancer in workers exposed to arsenic: a case control study].
Case-control methodology was used to assess lung cancer risk from exposure to arsenic in air, employing data from former workers in different units at the Chuquicamata copper mine and smelter complex. Thirty two workers from this complex were identified among the lung cancer deaths that occurred in the Northern region of Chile between 1987 and 1991. Each case was matched on age and sex, with controls that had a similar date of enrolment in the company. Available data on arsenic concentrations in air for six work sites were compiled from 1952 to 1991 and these were used to categorize the workplaces: Administrative area (1.6 micrograms/m3), Mine (2.3 micrograms/m3), Oxid Plant (3.1 micrograms/m3), Workshop and Services (9.8 micrograms/m3), Sulphur Plant (8.4 micrograms/m3) and Smelter (201.7 micrograms/m3). The results indicate an Odds Ratio of 5.7 (Fisher's p = 0.016) of dying from lung cancer among workers of the smelter compared with the rest of the workers.


Why consumers behave as they do with respect to food safety and risk information.
In recent years, it seems that consumers are generally uncertain about the safety and quality of their food and their risk perception differs substantially from that of experts. Hormone and veterinary drug residues in meat persist to occupy a high position in European consumers' food concern rankings. The aim of this contribution is to provide a better understanding to food risk analysts of why consumers behave as they do with respect to food safety and risk information. This paper presents some cases of seemingly irrational and inconsistent consumer behaviour with respect to food safety and risk information and provides explanations for these behaviours based on the nature of the risk and individual psychological processes. Potential solutions for rebuilding consumer confidence in food safety and bridging between lay and expert opinions towards food risks are reviewed. These include traceability and labelling, segmented communication approaches and public involvement in risk management decision-making.


Pulmonary versus systemic delivery of levofloxacin. The isolated lung of the rat as experimental approach for assessing pulmonary inhalation.
The present work was aimed to compare levofloxacin pulmonary disposition after systemic or inhalatory delivery and to evaluate the influence of respiratory pattern on lung distribution. An experimental model of the isolated lung of the rat was used. Twenty-four Wistar rats were distributed in four groups receiving levofloxacin under different experimental conditions including systemic or pulmonary delivery and higher or lower respiratory frequency with lower or higher tidal volume, respectively. Levofloxacin (500 microg) was administered as a bolus injection or by inhalation. Lung tissue samples as well as efferent and broncoalveolar fluid were collected. Quantification of levofloxacin levels in all samples was performed by a high-performance liquid chromatography (HPLC) technique. Pulmonary distribution coefficient of levofloxacin after systemic delivery showed mean values of 1.19+/-0.13 and 3.34+/-0.61 ml/g for each respiratory pattern assayed. The partition coefficients estimated from simultaneous drug level in lung tissue and efferent fluid (EF) are in agreement with the above values. Comparison of systemic and pulmonary administration reveals statistical significant differences between partition coefficients showing much higher values for the latter route (8.01+/-5.53 versus 2.86+/-1.35). In conclusion, inhalation compared to systemic administration improves levofloxacin access to the lung tissue; the experimental approach used here to assess the pulmonary drug disposition may be a useful model for biopharmaceutical studies of inhaled therapeutics.


Sepsis-Induced Coagulopathy and Disseminated Intravascular Coagulation.
Disseminated intravascular coagulation (DIC) has been recognized as a deadly complication in sepsis, and its early recognition followed by appropriate management of the underlying infection are the current management strategies. The activation of coagulation, inflammation, and other pathways are fundamental host responses against infection but also produce injury to the host. Recent advances have helped define the critical roles of thrombus formation in overcoming infection. In addition to activation of coagulation induced by pathogens, other important pathways including damage-associated molecular patterns, neutrophil extracellular traps, extracellular vesicles, and glycocalyx damage are involved in the pathogenesis of sepsis-induced DIC. The hallmark of DIC is thrombosis in the microvasculature; however, sepsis-induced DIC is a laboratory diagnosis based on coagulation test results and clinical setting. Although simplified criteria were recently introduced, DIC should be distinguished from other similar conditions such as thrombotic microangiopathy and heparin-induced thrombocytopenia. In DIC, treating the underlying cause is crucial, and additional adjunct therapies including antithrombin, thrombomodulin, and heparins may have potential benefit, but evidence supporting their use in terms of improvement of clinically relevant outcomes continues to be debated. In this review, we introduce recent findings regarding the pathophysiology, diagnosis, and treatment of sepsis-induced DIC. In addition, we also discuss future potential therapeutic approaches regarding this complex, life-threatening complication.


Affinity gels for purification of retinoid-specific binding protein (RSBP).
Retinoids are defined as compounds which elicit specific biological effects such as control of cell growth and cell differentiation by binding to a specific receptor. Recently, we demonstrated the presence of a protein (RSBP) which satisfies the criteria for the retinoid receptor. For purification of RSBP, we prepared two types of affinity gels with retinoidal ligands (Gel-Am and Gel-Ch) based on synthetic retinobenzoic acids which possess very potent retinoidal activities. RSBP in the crude fraction extracted from cultured cells could be purified about 300-fold by affinity column chromatography using these affinity gels.