[2-colored fluorescence of differentially condensed chromosomes stained with acridine orange].
Metaphase chromosomes of the Chinese hamster differentially-condensed under the influence of a) 5-bromdeoxyuridine, b) colcemide, and c) cold, were stained with acridine-orange (AO) in concentrations of 1.5 X 10(-7) to 3 X 10(-5) g/ml at pH 4.1 to 8.5. It was found that stretched chromosomal segments fluoresced in the orange/red part of the spectrum, whereas normally condensed ones--were green. The colour distribution along the chromosome depended mainly on the AO concentration and the exposure in the UV-light, and was independent of pH and molarity of the buffer. Apparently this phenomenon cannot be attributed to the uneven denaturation of the chromosomal DNA, but rather depends on structural and/or chemical differences between euchromatin and heterochromatin.


Usefulness and limitations of transesophageal echocardiography in the assessment of proximal coronary artery stenosis.
To assess the usefulness of transesophageal echocardiography in the evaluation of proximal coronary artery stenosis, 111 consecutive patients (mean age 61 years) who had intraoperative transesophageal echocardiography and coronary angiography within 1 week of surgery were studied. Transesophageal echocardiography visualized the entire length of the left main artery (0.2 to 2.2 cm, mean 0.93), 0.2 to 2.2 cm of the proximal left anterior descending artery and 0.1 to 3.4 cm of the proximal left circumflex artery in 103 patients (93%) and 0.1 to 4.6 cm of the proximal right coronary artery in 55 patients (49%). In the coronary artery segments visualized by echocardiography and compared with the corresponding angiographic segments, transesophageal echocardiography correctly identified 23 (96%) of 24 left main stenoses, 11 (78%) of 14 stenoses involving the left anterior descending artery, 6 (75%) of 8 left circumflex stenoses and all 7 stenoses (100%) of the right coronary artery. In all seven patients with ostial stenosis (left main artery in five and right coronary artery in two), the condition was correctly diagnosed by this technique. The sensitivity and specificity of transesophageal echocardiography in the overall evaluation of proximal coronary artery stenosis as customarily defined by angiography were 96% and 99% for the left main artery, 48% and 99% for the left anterior descending artery, 67% and 100% for the left circumflex artery and 37% and 100% for the right coronary artery, respectively. The distance of the stenotic lesion from the origin of the vessel by transesophageal echocardiography also correlated well with that measured by angiography (r = 0.63 to 0.99).(ABSTRACT TRUNCATED AT 250 WORDS)


A self-inflating tissue expander.
Tissue expansion is a means of mechanically creating an excess of soft tissue, contiguous to a defect, for use in reconstruction. To accomplish this, a self-inflating implant has been designed, tested, and used clinically. It offers potential advantages over similar percutaneously inflated devices, but has also presented new problems. Histologically, tissue expansion in the guinea pig is relatively innocuous, utilizing this implant; clinical results were similarly encouraging. Further clinical studies and applications await the identification of a more permeable membrane.


Tasks and routines in 21st century nursing: student nurses' perceptions.
The aim of this study was to explore final year nursing students' views about their clinical experiences. This was the second of three studies using a grounded theory approach overall with theoretical sampling of final year student nurses being chosen as a result of the initial study's findings. The sample was of a volunteer nature. The data collection tool was an open-ended questionnaire, with themes arising from the first study helping to form the questions. It was anticipated that more clinically experienced students would confirm, refute and perhaps provide "new" information about the reality of clinical nursing when compared with the sample of neophyte nurses from the first study. Data were analysed through initial coding of responses and then compared and contrasted to the data of study one. Findings included categories of views about the nurses' roles and tasks, clinical priorities of qualified nurses, holistic care, and care plans. The conclusion suggest that despite nursing theory proclaiming the advent of "new" nursing with hallmarks of holistic care and movement away from tasks and routines, the student nurses did not find this to be the case. Indeed, tasks and routines are what seemed to structure the work of nurses, with little evidence of holistic, patient-centred care occurring clinically.


Structure of pseudobactin A, a second siderophore from plant growth promoting Pseudomonas B10.
The structure of nonfluorescent pseudobactin A, one of two extracellular siderophores (microbial iron transport agents) produced by the plant growth promoting bacterium Pseudomonas B10, was determined by comparison of its 1H and 13C NMR spectra with those of yellow-green, fluorescent pseudobactin, the other siderophore. The molecular and crystal structure of ferric pseudobactin is reported in the preceding paper in this issue [Teintze, M., Hossain, M. B., Barnes, C. L., Leong J., & van der Helm, D. (1981) Biochemistry (preceding paper in this issue)]. The only structural difference between pseudobactin and pseudobactin A was that the latter was saturated at carbons 3 and 4 of the quinoline derivative, whereas pseudobactin is unsaturated at these positions. A mechanism is proposed for the observed conversion of pseudobactin A into pseudobactin in aqueous solution.


Predominance of influenza A(H3N2) virus genetic subclade 3C.2a1 during an early 2016/17 influenza season in Europe - Contribution of surveillance data from World Health Organization (WHO) European Region to the WHO vaccine composition consultation for northern hemisphere 2017/18.
During the European 2016/17 influenza season, A(H3N2) viruses have predominated and the majority clustered in genetic subclade 3C.2a1. Genetic analyses showed that circulating viruses have undergone considerable genetic diversification of the haemagglutinin gene from the current vaccine virus A/Hong Kong/4801/2014 (clade 3C.2a), but the antigenic data that is limited by the challenges with the antigenic characterisation of currently circulating A(H3N2) viruses, showed no clear evidence of antigenic change. The recommended A(H3N2) vaccine component for the northern hemisphere 2017/18 influenza season remained unchanged. However, early and mid-season vaccine effectiveness (VE) estimates were suggestive of reduced VE against A(H3N2) viruses.


Metoclopramide-induced movement disorders. Clinical findings with a review of the literature.
Metoclopramide, a dopamine-2 receptor antagonist used for various gastrointestinal disorders, may cause or exacerbate a variety of extrapyramidal movement disorders. To draw attention to the frequent occurrence of metoclopramide-induced movement disorders, we identified and studied 16 patients who had been exposed to this neuroleptic. The average age at onset was 63 years (range, 24 to 85 years), and women outnumbered men 3 to 1. Tardive dyskinesia was the most common movement disorder (n = 10 [63%]). Five patients had metoclopramide-induced parkinsonism, 1 patient had tardive dystonia, and 1 patient had akathisia. The average duration of exposure prior to onset of movement disorders was 12 months (range, 1 day to 4 years). Therapy was continued for an average of 6 months (range, 1 day to 2 years) after the onset of symptoms, reflecting clinical nonrecognition of the movement disorder and its relationship to metoclopramide. To prevent persistent and disabling movement disorders, long-term use of metoclopramide should be avoided, and patients should be carefully observed for potential neurologic reactions.


A video compression scheme with optimal bit allocation among segmentation, motion, and residual error.
We present a theory for the optimal bit allocation among quadtree (QT) segmentation, displacement vector field (DVF), and displaced frame difference (DFD). The theory is applicable to variable block size motion-compensated video coders (VBSMCVC), where the variable block sizes are encoded using the QT structure, the DVF is encoded by first-order differential pulse code modulation (DPCM), the DFD is encoded by a block-based scheme, and an additive distortion measure is employed. We derive an optimal scanning path for a QT that is based on a Hilbert curve. We consider the case of a lossless VBSMCVC first, for which we develop the optimal bit allocation algorithm using dynamic programming (DP). We then consider a lossy VBSMCVC, for which we use Lagrangian relaxation, and show how an iterative scheme, which employs the DP-based solution, can be used to find the optimal solution. We finally present a VBSMCVC, which is based on the proposed theory, which employs a DCT-based DFD encoding scheme. We compare the proposed coder with H.263. The results show that it outperforms H.263 significantly in the rate distortion sense, as well as in the subjective sense.


Meeting Abstracts - Academy of Managed Care Pharmacy Nexus 2019.
AMCP Nexus 2019: The Intersection of Value and Care, in National Harbor, MD, is expected to attract more than 2,400 managed care pharmacists and other health care professionals who manage and evaluate drug therapies, develop and manage networks, and work with medical managers and information specialists to improve the care of all individuals enrolled in managed care programs. The AMCP Abstracts program provides a forum through which authors can share their insights and outcomes of advanced managed care practice. Poster presentations are scheduled for Thursday, October 31, from 12:30 pm to 2:00 pm. For each poster, at least 1 author will be available during the poster presentations to discuss findings. Posters will also be displayed on Wednesday, October 30, from 4:30 pm to 6:30 pm, during the opening night reception in the Exchange. Podium presentations for the Platinum award-winning abstracts are Thursday, October 31, from 10:00 am to 11:30 am. Professional abstracts that have been reviewed are published in the Journal of Managed Care & Specialty Pharmacy's (JMCP) Meeting Abstracts supplement.


Looking inside the pores of a chromatographic column. I. Variation of the pore volume with mobile phase composition.
The dependence of void volume and pore volume on mobile phase composition was studied on a reversed phase column based on poly(divinyl benzene) in mobile phases consisting of 100% tetrahydrofuran (THF) and 40-90% THF-water. Void volumes V0 are obtained from a series of polymers with different molar mass by extrapolation of elution volume to M = 0, the interstitial volume Vi from the elution volume of polymers with a sufficiently high molar mass. The pore volume Vp is obtained as the difference (V0 - Vi). While Vi does not depend on mobile phase composition, a dramatic decrease of the pore volume is observed, when the mobile phase is changed from THF to THF-water. This effect of the mobile phase composition on the pore volume is observed using PEG and PPG as test macromolecules, regardless the retention mechanism: at 40-50% THF both PEG (in exclusion mode) and PPG (in adsorption mode) experience the same reduced pore volume, which is considerably lower than that in 100% THF.


Differential phosphorylation of two size forms of the neuronal class C L-type calcium channel alpha 1 subunit.
L-type calcium channels mediate long-lasting calcium currents which are modulated by protein phosphorylation. Using site-directed anti-peptide antibodies, we show that the alpha 1 subunit of the neuronal class C L-type calcium channel from rat brain exists in two size forms. The longer form, LC2, with an apparent molecular mass of 210-235 kDa was phosphorylated in vitro by cAMP-dependent protein kinase (cA-PK), but the shorter form, LC1, with an apparent molecular mass of 190-195 kDa was not a substrate for cA-PK. In contrast, LC1 and LC2 are both substrates for protein kinase C (PKC), calcium- and calmodulin-dependent protein kinase II, and cGMP-dependent protein kinase (cG-PK). The site-directed anti-peptide antibody CNC2 was produced against the COOH-terminal end of the class C L-type alpha 1 subunit as predicted by molecular cloning and sequencing of cDNA. CNC2 recognized LC2 but not LC1 by immunoblotting and immunoprecipitated only LC2 phosphorylated by either cA-PK or PKC. These results indicate that LC1 is truncated at its COOH-terminal end with respect to LC2 and that cA-PK preferentially phosphorylates sites in the COOH-terminal region of the alpha 1 subunit that are present in LC2 but not LC1. The selectivity of cA-PK for phosphorylation of the COOH-terminal region of LC2 suggests that the channel activities of the two alpha 1 subunit size forms may be differentially regulated by neurotransmitters and hormones which act through cAMP-dependent mechanisms, while both alpha 1 subunit isoforms may be modulated by PKC, cG-PK, and calcium- and calmodulin-dependent protein kinase II.


Patient evaluation and comparison of the recovery profile between propofol and thiopentone as induction agents in day surgery.
The patient's subjective perception of the quality of his/her recovery after day case anaesthesia with propofol or thiopentone as induction agents is still controversial. The authors investigated the perception and quality of awakening after anaesthesia during the recovery period and at 24 hours and 72 hours, in outpatients undergoing anaesthesia induced either with propofol or thiopentone and maintained with a volatile anaesthetic. In a double-blind study in adults undergoing knee arthroscopy in a day surgery unit, propofol and thiopentone were compared as induction agents in 60 randomized outpatients. A Critical Flicker Fusion Threshold test (CFFT), verbal test for anxiety, visual analog scale for anxiety and pain, and questionnaires were used to assess objectively and subjectively the quality of anaesthesia and awakening during the postoperative period. Demographic data and mean duration of anaesthesia were similar. In the propofol group, patients awoke more rapidly (9.2 +/- 5.8 vs 12.3 +/- 5.8 min) (P < 0.05); however, the CFFT measurements did not show any significant difference between the groups, except at time = 0 min, when 17 patients in the propofol group were able to perform the test versus only 10 patients in the thiopentone group (P < 0.05). At 4, 24, and 72 hours postoperatively, the authors were unable to detect any difference between the two groups. Except for early recovery, there were no differences between the intermediate and late recovery profiles, when propofol or thiopentone was used as the anaesthetic induction agent in day surgery.


Airway response to acid instillation in esophagus in bronchial asthma.
An increased incidence of gastroesophageal reflux has been reported in patients with bronchial asthma. We studied the pulmonary effects of acid instillation in the esophagus. Fifteen patients with bronchial asthma and 15 healthy adults in the age group 15-50 years were studied. The control subjects were first screened for bronchial hyperreactivity by a methacholine challenge test. Patients and controls were both subjected to modified Bernstein test. Spirometry was done at baseline and after each instillation of either acid or saline. Respiratory and reflux symptoms were noted after each infusion and antacid administration. Five patients and one control subject had history of reflux symptoms (p < 0.05) and six patients had nocturnal asthma. There was a significant fall in FEV1/FVC after acid infusion patients; this improved significantly after antacid administration. All six patients with nocturnal asthma had respiratory signs or symptoms and had more than 20% fall in FEV1 on acid instillation in the esophagus, while none in the control group developed the same. Gastroesophageal reflux occurs more frequently in patients with bronchial asthma and acid instillation in the esophagus triggers bronchoconstriction.


A further development of the QNAR model to predict the cellular uptake of nanoparticles by pancreatic cancer cells.
Nanotechnology has led to the development of new nanomaterials with unique properties and a wide variety of applications. In the present study, we focused on the cellular uptake of a group of nanoparticles with a single metal core by pancreatic cancer cells, which has been studied by Yap et al. (Rsc Advances, 2012, 2 (2):8489-8496) using classification models. In this work, the development of a further Quantitative Nanostructure-Activity Relationship (QNAR) model was performed by linear multiple linear regression (MLR) and nonlinear artificial neural network (ANN) techniques to accurately predict the cellular uptake values of these compounds by dividing them into three groups. Judging from the attained statistical results, our derived QNAR models have an acceptable overall accuracy and robustness, as well as good predictivity on the external data sets. Moreover, the results of this study provide some insights on how engineered nanomaterial features influence cellular responses and thereby outline possible approaches for developing and applying predictive computational models for biological responses caused by exposure to nanomaterials.


Gastrointestinal bleeding in von Willebrand disease.
Gastrointestinal bleeding due to colonic angiodysplasia is a well-recognised complication of von Willebrand disease (vWD), occurring almost exclusively in subtypes of the disease associated with a reduction in high-molecular-weight (HMW) multimers of von Willebrand factor (vWF). A deficiency of vWF HMW multimers also provides the link between aortic stenosis and gastrointestinal (GI) bleeding in Heyde's syndrome. The diagnosis and treatment of the angiodysplastic bleeding in vWD can be very difficult and the role of vWF containing concentrates in treatment and prophylaxis remains to be established.


Effects of exercise-training on cardiac performance and muscle enzymes in rainbow trout,Oncorhynchus mykiss.
Rainbow trout,Oncorhynchus mykiss, were exercise-trained for 18 hours per day over 28 days at water velocities up to 60% of their measured Ucrit. Anin situ perfused heart preparation was used to compare maximum cardiac performance between control and trained fish. Trained fish had a larger stroke volume at a given filling pressure, as well as an 18% higher cardiac output and a 25% greater maximum power output. These observations indicate that exercise training in rainbow trout improved maximum cardiac performance. Adrenaline produced positive inotropic and chronotropic effects on the perfused heart, but exercise training did not alter these stimulatory effects. Maximal activities of citrate synthase (CS), B-hydroxyacyl CoA dehydrogenase (HOAD), glutamate dehydrogenase (GDH) and carnitine palmitoyl transferase (CPT) were measured in cardiac and skeletal muscles. CS, HOAD and GDH increased in red and white skeletal muscle as a result of training. Training also increased GDH activity in the endocardium and epicardium, and increased HOAD in the epicardium. While the training regime did not result in a statistically significant increase in Ucrit and produced a decrease in the condition factor of the fish, other training effects were clearly evident. Furthermore, significant correlations were observed between Ucrit and the maximal activities of GDH and HOAD.


Epidural analgesia following upper abdominal surgery: United Kingdom practice.
Epidural Analgesia (EA) may be used to provide pain relief after upper abdominal surgery. A variety of drugs and combinations may be used. Potential side effects lead some to believe EA should be restricted to high care areas. The use of EA following upper abdominal surgery is surveyed in 214 hospitals in the United Kingdom by means of a postal questionnaire. Sixty-seven percent use EA frequently and 3% not at all. The low thoracic site is the most commonly used, by 65%. Forty-eight percent use a combination of sites. EA is most frequently achieved using a mixture of an opioid and a local anaesthetic (97%). No other agents are used. Fentanyl and diamorphine are the opioids used most widely (61% and 52% departments, respectively) in combination with local anaesthetic. Subcutaneous heparin is regularly used in 89% of departments. In 43%, the epidural is sited shortly after administering heparin. Use of EA is restricted solely to intensive or high-care units in 46% of hospitals. In 82% of departments, EA is continued for up to 72 h. Ninety-six percent of departments use continuous epidural infusions in the post-operative period. Adjunct analgesia includes non-steroidal anti-inflammatory drugs in 50% of departments. An anaesthetist supervises EA in 89% of hospitals. EA is considered to be the best mode of analgesia available by 80% of respondents. EA is widely used in the United Kingdom following upper abdominal surgery. A degree of consensus exists on the choice of drug types, their method of administration and duration. There is no consensus as to whether the technique should be used on a general ward, which opioid should be used or the timing of heparin.


Incidence of heart failure and mortality after acute coronary syndromes.
The long-term incidence of heart failure (HF) in ST-elevation myocardial infarction (STEMI), non-ST-elevation myocardial infarction (NSTEMI), or unstable angina (UA) patients is uncertain. We examined the 1-year incidence of HF and its association with mortality among patients surviving their first acute coronary syndrome (ACS) hospitalization. A retrospective cohort study of patients, aged ≥20 years, with no prior HF, hospitalized for the first time with ACS between April 1, 2002, and December 31, 2008, in Alberta, Canada, and followed up for 1 year. Index HF was defined as HF that developed as a complication during the index ACS hospitalization, and post-discharge HF, as HF developing after discharge from the index ACS hospitalization. Among 9,406 STEMI, 11,008 NSTEMI, and 4,910 UA patients, 13.6%, 14.8%, and 5.2% had index HF, respectively (P < .01). At 1-year, cumulative HF rates were 23.4% in STEMI, 25.4% in NSTEMI, and 16% in UA patients. Among hospital survivors, 1-year mortality rate was 13.9% in patients with index HF, 10.6% in patients with postdischarge HF, and 2.4% in patients with no HF. In multivariable analysis, both index HF (adjusted hazard ratio 3.2, 95% CI 2.7-3.7) and postdischarge HF (adjusted hazard ratio 4.6, 95% CI 3.9-5.4) were associated with 1-year mortality. There are significant differences in the incidence of HF among STEMI, NSTEMI, and UA patients. The increased mortality risk associated with index HF and postdischarge HF suggests a need for vigilant follow-up of all ACS patients for prompt detection and treatment of HF.


PACAP peptides modulate guinea pig cardiac neuron membrane excitability and neuropeptide expression.
Morphological studies identified PACAP-immunoreactive nerve fibers in dense pericellular arrangements around virtually every cholinergic parasympathetic neuron of guinea pig cardiac ganglia; all postganglionic cardiac neurons expressed membrane-associated PAC1 receptor protein. Characterization of the alternative splice variants established predominant expression of the PAC1(very short) receptor transcript containing neither HIP nor HOP exons. PACAP depolarized cardiac neurons and increased membrane excitability; the excitability resulted from neither altered action potential properties nor inhibition of IM. Treatment of cardiac ganglia explants with PACAP significantly reduced the numbers of cholinergic neurons coexpressing somatostatin immunoreactivity, which did not appear to be correlated with prosomatostatin mRNA expression. The PACAP-mediated decrease in somatostatin immunoreactive neurons required calcium influx through L-type calcium channels and activation of adenylyl cyclase, whereas activation of phospholipase C or protein kinase A was not required. These observations indicate that PACAP through the PAC1 receptors elicits complex actions on guinea pig parasympathetic cardiac ganglia neurons, including modulation of membrane ion conductances and modulation of neuropeptide expression.


Severely Affected by Parkinson Disease: The Patient's View and Implications for Palliative Care.
People severely affected by Parkinson disease (PD)/atypical parkinsonism (AP) comprise a heterogeneous group with distinct needs, which so far remain largely unexamined. The aim of our study was to analyze reasons for feeling severely affected and document unmet needs in a patient subgroup severely affected by PD/AP using solely a subjective inclusion criterion. Patients feeling severely affected by PD/AP were recruited via a magazine published by the German Parkinson Association. A questionnaire was sent out nationwide. Besides analyzing the closed-ended questions, a subsample of 40% was analyzed regarding the open-ended questions using content analysis. Correlations between subjectively felt severe affectedness and objective criteria were calculated. Eight hundred fourteen questionnaires were analyzed. Sample characteristics were: mean age 70 years; 60.3% male; time since diagnosis up to 37 years; and Hoehn and Yahr score (if known) 3 (44.6%), followed by 4 (23.9%). Significant associations were observed between subjectively felt severe affectedness and Hoehn and Yahr ( P ≤ .05), poorer health ( P ≤ .01), higher nursing care level ( P ≤ 0.01), and having no children ( P ≤ .05). Most common reasons for feeling severely affected were mobility impairment (34.9%), coordination problems (17.0%), speech problems (12.2%), and limited day-to-day activities (7.8%). Most often expressed unmet needs were support in everyday life (28.1%), medical treatment (15.2%), help with financial services (11.6%), and social integration (9.9%). To meet the complex needs, an integrated multidisciplinary and multiprofessional approach is indicated befitting palliative care principles. Herein, home-based services seem of special importance for patients in advanced disease stages.


Nonlinear control of an activated sludge aeration process: use of fuzzy techniques for tuning PID controllers.
In this paper, several tuning algorithms, specifically ITAE, IMC and Cohen and Coon, were applied in order to tune an activated sludge aeration PID controller. Performance results of these controllers were compared by simulation with those obtained by using a nonlinear fuzzy PID controller. In order to design this controller, a trial and error procedure was used to determine, as a function of error at current time and at a previous time, sets of parameters (including controller gain, integral time and derivative time) which achieve satisfactory response of a PID controller actuating over the aeration process. Once these sets of data were obtained, neural networks were used to obtain fuzzy membership functions and fuzzy rules of the fuzzy PID controller.


[Postoperative adjuvant immunochemotherapy using Lentinan for advanced gastric carcinoma patients with metastasis in the regional lymph nodes and serosal invasion].
Six patients with gastric cancer, stage IIIA to IV, received intraabdominal cisplatin (CDDP) at laporotomy. This was followed by postoperative intravenous infusion of mitomycin C (MMC), CDDP or fluorouracil (5-FU). When these patients recovered to the extent that permitted oral medication, an immunochemotherapeutic regimen containing either oral UFT (uracil and tegafur) or 5'-deoxy-5-fluorouridine (5'-DFUR), plus intravenous Lentinan (LNT) was administered for a period ranging from one and a half to two years. This postoperative immunochemotherapy was successful in all 6 patients. No relapse has been observed in any of them for at least 4 years. These findings indicate that the chemotherapeutic strategy of administering intraabdominal CDDP immediately after surgery, followed by postoperative immunochemotherapy with pyrimidine-fluoride products plus Lentinan on an outpatient basis may be useful in the treatment of T3 or T4 gastric carcinoma with metastasis in the regional lymph nodes.


[Experimental modeling of jaw bones for dental implantation].
As the result of morphometric study the structural correspondence of the cortical layer and cells' volume surface between jaw segments and some osseous skeletal structures was found. These pairs included zones of lower incisors and parietal bone, zones of upper incisors/lower premolars and ribbon, zones of upper premolars/lower molars and huckle-bone crest, zones of upper molars and handle and body of sternum. Received data let us use the above mentioned osseous objects as the model for experimental studies on jaw bones.


The Soviet country profile: health of the U.S.S.R. population in the 70s and 80s--an approach to a comprehensive analysis.
This paper reviews data from 1970 onwards on the distribution of health resources and health status for urban and rural areas and for the 15 Soviet republics. Major disparities exist between republics and especially between the European republics in the North and West and those of Central Asia and Transcaucasia. The former show relatively low infant death rates but high adult mortality, particularly for middle-aged males; rates of death due to circulatory diseases and malignant neoplasms have increased in these republics and special studies reveal a high incidence of alcohol-related diseases. In contrast, the Central Asian and Transcaucasian republics have extremely high infant mortality but high levels of life-expectancy thereafter. An index of medical inequality shows a much lower level of resources in these republics. Recent long-term strategies are described which aim to raise the income and status of health personnel from their relatively low levels and to equalize the distribution of health care across the country.


[Acute limb ischemia].
Despite major advances in the contemporary management of peripheral arterial occlusive disease, acute ischemia of the lower limb is still characterized by an important morbidity, limb threat, and mortality, and continues to pose a challenge to the vascular surgeon. Ageing of the population increases the prevalence of acute lower limb ischemia. The two principal etiologies of acute ischemia of the lower limbs are arterial embolism and in situ thrombosis of an atherosclerotic artery or of a bypass graft. Popliteal aneurysm thrombosis and vascular trauma are less common causes of severe limb ischemia. Prompt recognition and treatment of acute limb ischemia in an urgent setting are crucial, in order to shorten as much as possible the duration of the ischemia. This paper highlights diagnostic work-up (staging of the severity of ischemia) and appropriate management of acute ischemia of the lower limb. Different procedures of revascularization (operative clot removal, catheter-directed thrombolysis, bypass grafting are evaluated and their outcome results are compared.


Testing for temporal variation in diversification rates when sampling is incomplete and nonrandom.
A common pattern found in phylogeny-based empirical studies of diversification is a decrease in the rate of lineage accumulation toward the present. This early-burst pattern of cladogenesis is often interpreted as a signal of adaptive radiation or density-dependent processes of diversification. However, incomplete taxonomic sampling is also known to artifactually produce patterns of rapid initial diversification. The Monte Carlo constant rates (MCCR) test, based upon Pybus and Harvey's gamma (γ)-statistic, is commonly used to accommodate incomplete sampling, but this test assumes that missing taxa have been randomly pruned from the phylogeny. Here we use simulations to show that preferentially sampling disparate lineages within a clade can produce severely inflated type-I error rates of the MCCR test, especially when taxon sampling drops below 75%. We first propose two corrections for the standard MCCR test, the proportionally deeper splits that assumes missing taxa are more likely to be recently diverged, and the deepest splits only MCCR that assumes that all missing taxa are the youngest lineages in the clade, and assess their statistical properties. We then extend these two tests into a generalized form that allows the degree of nonrandom sampling (NRS)to be controlled by a scaling parameter, α. This generalized test is then applied to two recent studies. This new test allows systematists to account for nonrandom taxonomic sampling when assessing temporal patterns of lineage diversification in empirical trees. Given the dramatic affect NRS can have on the behavior of the MCCR test, we argue that evaluating the sensitivity of this test to NRS should become the norm when investigating patterns of cladogenesis in incompletely sampled phylogenies.


[Chronic non-communicable diseases in Brazil: priorities for disease management and research].
Chronic Non-Communicable Diseases are the main source of disease burden in Brazil. In 2011, the Brazilian Ministry of Health launched the Strategic Plan of Action for Management of Chronic Non-Communicable Diseases focusing on population-based interventions to manage cardiovascular diseases, diabetes, cancer, and chronic respiratory diseases mainly through fighting tobacco use, unhealthy diets, physical inactivity and the harmful use of alcohol. Although a significant number of scientific studies on chronic diseases and their risk factors have been undertaken in Brazil, few are of cohort design. In this context, the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), a cohort study of 15,105 Brazilian public servants reflects the reality of high prevalences of diabetes, hypertension and the main chronic diseases risk factors. The diversity of information that the Study will produce can provide important input to better understand the causes of chronic diseases and to support public policies for fighting them.


Nlcam modulates midline convergence during anterior neural plate morphogenesis.
During development, different cell types must undergo distinct morphogenetic programs so that tissues develop the right dimensions in the appropriate place. In early eye morphogenesis, retinal progenitor cells (RPCs) move first towards the midline, before turning around to migrate out into the evaginating optic vesicles. Neighbouring forebrain cells, however, converge rapidly and then remain at the midline. These differential behaviours are regulated by the transcription factor Rx3. Here, we identify a downstream target of Rx3, the Ig-domain protein Nlcam, and characterise its role in regulating cell migration during the initial phase of optic vesicle morphogenesis. Through sophisticated live imaging and comprehensive cell tracking experiments in zebrafish, we show that ectopic expression of Nlcam in RPCs, as is observed in Rx3 mutants, causes enhanced convergence of these cells. Expression levels of Nlcam therefore regulate the migratory properties of RPCs. Our results provide evidence that the two phases of optic vesicle morphogenesis: slowed convergence and outward-directed migration, are under different genetic control. We propose that Nlcam forms part of the guidance machinery directing rapid midline migration of forebrain precursors, where it is normally expressed, and that its ectopic expression upon loss of Rx3 imparts these migratory characteristics upon RPCs.


Isolation and Structural Characterization of Echinocystic Acid Triterpenoid Saponins from the Australian Medicinal and Food Plant Acacia ligulata.
The Australian plant Acacia ligulata has a number of traditional food and medicinal uses by Australian Aboriginal people, although no bioactive compounds have previously been isolated from this species. Bioassay-guided fractionation of an ethanolic extract of the mature pods of A. ligulata led to the isolation of the two new echinocystic acid triterpenoid saponins, ligulatasides A (1) and B (2), which differ in the fine structure of their glycan substituents. Their structures were elucidated on the basis of 1D and 2D NMR, GC-MS, LC-MS/MS, and saccharide linkage analysis. These are the first isolated compounds from A. ligulata and the first fully elucidated structures of triterpenoid saponins from Acacia sensu stricto having echinocystic acid reported as the aglycone. Compounds 1 and 2 were evaluated for cytotoxic activity against a human melanoma cancer cell line (SK-MEL28) and a diploid fibroblast cell line (HFF), but showed only weak activity.


Traumatic hip dislocation in children. Long-term followup of 42 patients.
To assess the impact of traumatic hip dislocations in the skeletally immature patient, 42 children younger than 16 years of age (average age, 9 years 10 months) who were treated at the authors' institution were studied. Data were collected from charts and radiographs and by completion of questionnaires. The average followup after injury was 10 years 1 month. The majority of dislocations (64%) were attributable to low energy injuries. Ipsilateral fractures about the hip occurred in 17% of patients. Avascular necrosis of the femoral head developed in 12% of patients, with the amount of time spent dislocated being the only statistically proven risk factor. Patients whose reduction was delayed greater than 6 hours had a 20 times higher risk of having avascular necrosis develop compared with patients whose hips were reduced in 6 hours or less. The use of computed tomography for joint asymmetry of 3 mm or greater and omission of bone scan screening were supported by this study. Functional outcomes were very good in this series with 95% of patients suffering mild (usually weather related) or no pain and 95% of patients suffering mild pain (intermittently noticeable) or no limp. A large percentage of the patients (78%) continued to participate in high demand activities such as football, soccer, and basketball.


Phenytoin dosing in obese patients: two case reports.
Phenytoin is used extensively in the treatment of various forms of epilepsy, and remains the drug of choice in partial and generalized tonic-clonic seizures. Because it demonstrates saturable, Michaelis-Menten pharmacokinetics, dosing of phenytoin within the therapeutic range can be very challenging, especially so in obese patients. We present case reports of two obese patients each requiring very large doses of phenytoin sodium (1000 mg/d) to sustain therapeutic serum concentrations and seizure control. There are very few reports in the literature regarding phenytoin pharmacokinetic changes in the obese. We can only theorize possible changes in these parameters. Further investigation in the form of controlled research trials need to be performed before final dosage recommendations can be given.


Bilharzial endocervical polyp.
Schistosomiasis still represents a major threat to women's health in many developing countries. The frequency in developed countries is increasing among immigrants and tourists who have a history of freshwater exposure in endemic areas. This is a case of 43-year-old immunocompetent Egyptian woman presented by abnormal vaginal bleeding. The gynecological examination revealed an endocervical polyp measuring 3 x 2 x 1 cm. Polypectomy was done. Histopathological examination revealed several granulomas containing viable eggs of Schistosoma hematobium. Schistosomiasis is rarely presented with endocervical polyp. In developing countries, schistosomiasis may be considered in differential diagnosis of patient with endocervical polyp.


Posterior horn medial meniscal root repair with cruciate ligament/medial collateral ligament combined injuries.
Many meniscal root tears remain unrepaired, potentially due to under-recognition and the technical challenge of repairing them. A great effort is made to preserve the native meniscus and restore the circumferential fibers for hoop stress resistance. It has been well demonstrated in the literature that failure to repair this will lead to increased contact pressures in the medial compartment and early degenerative changes in the articular cartilage. Our technique is one that allows the meniscus to resume its important role of knee stability. A thorough understanding of meniscal root anatomy, as well as repair techniques, is important for the cruciate ligament surgeon.


AHRQ's hospital survey on patient safety culture: psychometric analyses.
This project analyzed the psychometric properties of the Agency for Healthcare Research and Quality Hospital Survey on Patient Safety Culture (HSOPSC) including factor structure, interitem reliability and intraclass correlations, usefulness for assessment, predictive validity, and sensitivity. The survey was administered to 454 health care staff in 3 hospitals before and after a series of multidisciplinary interventions designed to improve safety culture. Respondents (before, 434; after, 368) included nurses, physicians, pharmacists, and other hospital staff members. Factor analysis partially confirmed the validity of the HSOPSC subscales. Interitem consistency reliability was above 0.7 for 5 subscales; the staffing subscale had the lowest reliability coefficients. The intraclass correlation coefficients, agreement among the members of each unit, were within recommended ranges. The pattern of high and low scores across the subscales of the HSOPSC in the study hospitals were similar to the sample of Pacific region hospitals reported by the Agency for Healthcare Research and Quality and corresponded to the proportion of items in each subscale that are worded negatively (reverse scored). Most of the unit and hospital dimensions were correlated with the Safety Grade outcome measure in the tool. Overall, the tool was shown to have moderate-to-strong validity and reliability, with the exception of the staffing subscale. The usefulness in assessing areas of strength and weakness for hospitals or units among the culture subscales is questionable. The culture subscales were shown to correlate with the perceived outcomes, but further study is needed to determine true predictive validity.


Deconstructing dementia and delirium hospital practice: using cultural historical activity theory to inform education approaches.
Older patients with dementia and delirium receive suboptimal hospital care. Policy calls for more effective education to address this though there is little consensus on what this entails. The purpose of this clarification study is to explore how practice gaps are constructed in relation to managing the confused hospitalised older patient. The intent is to inform educational processes in the work-place beyond traditional approaches such as training. Adopting grounded theory as a research method and working within a social constructionist paradigm we explored the practice gaps of 15 healthcare professionals by interview and conducted five focus groups with patients, carers and Liaison mental health professionals. Data were thematically analysed by constant comparison and theoretical sampling was undertaken until saturation reached. Categories were identified and pragmatic concepts developed grounded within the data. Findings were then further analysed using cultural historical activity theory as a deductive lens. Practice gaps in relation to managing the confused older patient are determined by factors operating at individual (knowledge and skill gaps, personal philosophy, task based practice), team (leadership, time and ward environmental factors) and organisational (power relationships, dominance of medical model, fragmentation of care services) levels. Conceptually, practice appeared to be influenced by socio-cultural ward factors and compounded by a failure to join up existing "patient" knowledge amongst professionals. Applying cultural historical activity theory to further illuminate the findings, the central object is defined as learning about the patient and the mediating artifacts are the care relationships. The overarching medical dominance emerges as an important cultural historical factor at play and staff rules and divisions of labour are exposed. Lastly key contradictions and tensions in the system that work against learning about the patient are identified. Cultural historical activity theory can be used to advance understanding of practice gaps in order to develop a broader transformative approach to dementia and delirium practice and education. Structural changes at an individual, team and systems level resulting from this novel understanding of practice complexity are proposed. Contradictions can be used as foci for expansive learning. Lastly, interprofessional education (formal and informal) is advocated to further knotwork and improve the care of the older confused patient.


Impaired suppressor cell activity due to surface sulphydryl oxidation in rheumatoid arthritis.
Rheumatoid arthritis is a chronic inflammatory disorder with considerable evidence of impaired regulation of the immune response, including defective suppressor cell function, especially in the synovial membrane. We have investigated whether oxidation of cell surface thiols might be responsible for these defects and whether such cell function may be modulated towards normal by treatment with a sulphydryl-reactive drug, D-penicillamine. Using healthy mononuclear cells treated with an impermeant thiol blocker, induction of suppressor activity by incubation with the lectin Con A was not dependent on surface sulphydryl groups but suppressor activity was abolished by thiol blockade after Con A stimulation. Peripheral blood mononuclear cells from patients with active rheumatoid disease showed impaired Con A-induced suppressor activity which was enhanced to near-normal levels by incubating the rheumatoid cells with a sulphydryl reducing agent, 2-mercaptoethanol, or D-penicillamine. Con A-stimulation of cells from patients treated with intramuscular gold or D-penicillamine generated more active suppression than those from patients receiving non-steroidal drugs only. Mononuclear cells from patients with other chronic inflammatory joint diseases showed normal Con A-induced suppressor activity. These data support the conclusion that surface thiols on mononuclear cells in rheumatoid arthritis are reversibly oxidized by the disease process. This gives rise to aberrant cell function including impaired suppressor activity. Such a mechanism may be at least partly responsible for the defective immunoregulation seen in rheumatoid patients and thus be a relevant target for thiol containing antirheumatic drugs.


Probing the proposed phenyl-A region of the sigma-1 receptor.
The proposed phenyl-A region of sigma (sigma) receptors accommodates several structural features. In this study we explored the possibility that appropriate structural features located at the phenyl-A region of sigma receptor sites could lead to more potent and selective agents for the sigma receptor subtypes. By keeping the phenyl-B substituent as the optimum omega-phenylpentyl moiety, and varying substituents in the phenyl-A region, we have observed changes in binding potency and selectivity at the sigma receptor subtypes. SAR for the binding of these compounds at sigma-2 sites was also examined.


DESIGN, SYNTHESIS AND BIOLOGICAL EVALUATION OF 2,3-DISUBSTITUTED AND FUSED QUINOXALINES AS POTENTIAL ANTICANCER AND ANTIMICROBIAL AGENTS.
This article describes the synthesis of new bioactive quinoxalines as potential anticancer and antimicrobial agents; 2,3-dichloroquinoxaline was used as the key molecule for the preparation of various mono or disubstituted quinoxalines 2-7, pyridoimidazoquinoxaline derivative 8, thiazolo[4,5-b]quinoxaline derivatives 9-11, piperazinoquinoxaline derivatives 12, 13 and 1,4-benzoxazino[2,3-b]quinoxaline 15. The newly synthesized compounds were evaluated for their anticancer and antimicrobial activity. Assay results showed the compounds 6-bromo-2-chloro-N-[4-(trifluoromethyl)phenyl]-3-aminoquinoxaline (4), 7-bromo-2-[2-(4-methoxy-benzylidene) hydrazinyl]thiazolo[5,4-b]quinoxaline (9d) and 7-bromo-1,2,3,4-tetrahydropyrazino[2,3- blquinoxaline (12) proved to possess dual effects as potential anti-cancer and antimicrobial agents.


Accuracy of volume measurements of computed tomography and magnetic resonance imaging phantoms by three-dimensional reconstruction and preliminary clinical application.
Using an independent three-dimensional workstation, the accuracy of volume measurements of phantoms was assessed using three-dimensional reconstruction of two-dimensional computed tomography (CT) and magnetic resonance (MR) images. Round, cylindrical, and irregularly shaped high-contrast phantoms of known volume were imaged in a water bath. The effect of object contrast on volume estimation was tested using phantoms of known volume diluted serially with a contrast agent. The effect of changing field of view and slice thickness was assessed. A clinical application was performed, in which nine shoulders were injected with a known quantity of contrast material, to test the accuracy of the technique in vivo. A strong paired correlation (r = .99) between estimated and true volumes was obtained for high-contrast phantoms ranging from 17 to 128 mL. The weighted average absolute error was 1.42 mL (MR) and 3.50 mL (CT). Accuracy of the serially diluted 27-mL phantoms was essentially unaffected by contrast differences greater than 133 units (MR) and 102 units (CT). The weighted average absolute error was 1.33 mL (MR) and 1.56 mL (CT). Changing field of view had no effect on accuracy, but increasing the slice thickness resulted in over-estimation of volume. The mean error for the clinical application was 4.4% (range: 1.7%-8.3%). Under certain circumstances, three-dimensional reconstructive volume estimation can be a convenient and accurate method for volume determination.


Excess dietary fluoride affects laying performance, egg quality, tissue retention, serum biochemical indices, and reproductive hormones of laying hens.
The present study aimed to evaluate the effects of excess dietary fluoride (F) on laying performance, egg quality, tissue retention, serum biochemical indices, and serum reproductive hormones of laying hens. A total of 384 Hy-Line Gray hens, 37 wk old, were treated with sodium fluoride added to a corn-soybean meal basal diet at 0, 400, 800, and 1200 mg fluorine/kg feed. The results showed that dietary F levels at 800 and 1200 mg/kg markedly decreased ADFI, laying rate, average egg weight, and increased feed conversion ratio (FCR) (P < 0.05). Dietary F levels at 800 and 1200 mg/kg dramatically decreased the egg quality of albumen height, yolk color, eggshell strength, and eggshell thickness, and on the 49th D, 400 mg/kg F group significantly decreased the eggshell strength, compared to those of control group. Fluoride residues in tissues of hens were increased significantly with the increase of dietary F supplemental levels (P < 0.05). Fluoride concentrations were generally high in feces, eggshell, tibia, kidney, and ovary, and the highest in feces, following with eggshell and tibia, lower in kidney and ovary, and the lowest in serum. Serum uric acid levels and alanine aminotransferase activity increased significantly (P < 0.05), and glucose, triglycerides, and phosphorus decreased significantly (P < 0.05) in response to dietary F concentration, compared to those of the control group, respectively. Dietary F supplementation at 1200 mg/kg significantly decreased (P < 0.05) the estrogen concentrations in serum, compared to those of the control group. Concentrations of progesterone in the fluoride-treated groups were significantly (P < 0.05) decreased relative to those of the control group. In conclusion, these results indicated that the excessive ingestion of F has had a detrimental effect on egg laying rate and quality of eggs by damaging the function of the liver, kidney, and ovary of laying hens.


Modulation of inflammatory response after spinal cord trauma with deferoxamine, an iron chelator.
The standard iron-chelator deferoxamine is known to reduce neurological deficits. The aim of the present study was to evaluate the contribution of deferoxamine in the secondary damage in experimental spinal cord injury (SCI) in mice, induced by the application of vascular clips to the dura via a four-level T5-T8 laminectomy. SCI resulted in production of inflammatory mediators, tissue damage and apoptosis. Deferoxamine treatment 30 min before and 1 and 6 h after the SCI significantly reduced: (1) GFAP immunoreactivity, (2) neutrophil infiltration, (3) NF-kappaB activation, (4) iNOS expression, (5) nitrotyrosine and MDA formation, (6) DNA damage (methyl green pyronin staining and PAR formation and (7) apoptosis (TUNEL staining, FasL, Bax and Bcl-2 expression, S-100 expression). Moreover, deferoxamine significantly ameliorated the recovery of limb function (evaluated by motor recovery score). Taken together, the results clearly demonstrate that deferoxamine treatment reduces the development of inflammation and tissue injury associated with spinal cord trauma.


Model for medication therapy management in a university clinic.
Experience with a referral-based medication therapy management (MTM) clinic in a university medical center is described. The MTM clinic's mission is to assist patients who take multiple medications due to multiple chronic conditions with the management of their drug therapy to improve or maintain their health and prevent or minimize drug-related problems. The clinical services provided at the clinic have evolved into a comprehensive program providing five distinct service areas: access, adherence, coordination of care, medication therapy review, and education. During initial visits, patient information is collected, patients are interviewed, medications are reconciled, and the pharmacist identifies and attempts to solve any immediate drug-related problems and concerns. Routine visits are scheduled monthly to coincide with a patient's medication refills. On a typical day, a minimum of two MTM pharmacists and one pharmacy technician staff the clinic. On two days of the week, three MTM pharmacists are available in the clinic. The clinic averages 9-13 scheduled patient visits per day. The MTM clinic functions as a subset of the outpatient pharmacy and is merged financially in the general operational budget of the ambulatory care pharmacy. This model of MTM patient care is intensive and comprehensive and is significantly different from the majority of MTM models currently provided by Medicare Part D plans. A referral-based MTM clinic managed by pharmacists at a university medical center outpatient pharmacy provides care to patients with the goal of improving medication access, medication adherence, continuity of care, medication therapy management, and patient education.


Globotriaosylceramide (Gb3) content in HeLa cells is correlated to Shiga toxin-induced cytotoxicity and Gb3 synthase expression.
Globotriaosylceramide (Gb3) and globotetraosylceramide (Gb4) are the proposed functional receptors for Shiga toxin (Stx). To elucidate the effect of Gb3 content on Stx-induced cytotoxicity in HeLa cells, we cloned HeLa cells and determined the correlation between glycolipids content and Stx-induced cytotoxicity. The 29 HeLa cell clone (HLCC) lines used showed a wide range of sensitivity to Stx, compared to Gb3-rich cells which were more sensitive, showing as little as 20% viability to 100 pg/ml Stx. In contrast, Gb3-deficient cells proved resistant as they were more than 80% viable to 100 ng/ml Stx. Gb3 content in the HLCC lines corresponded with Stxs-induced cytotoxicity as well as Gb3 synthase expression, but no correlation with Gb4 content was noted. These data show that Gb3 content, which is regulated by the expression of Gb3 synthase, determines the sensitivity of HeLa cells toward Stx.


Quasi-ice monolayer on atomically smooth amorphous SiO2 at room temperature observed with a high-finesse optical resonator.
The structure of an H(2)O monolayer bound to atomically smooth hydroxylated amorphous silica is probed under ambient conditions by near-infrared evanescent-wave cavity ring-down absorption spectroscopy. Employing a miniature monolithic optical resonator, we find sharp (approximately 10 cm(-1)) and polarized (>10:1) vibration-combination bands for surface OH and adsorbed H(2)O, which reveal ordered species in distinct local environments. Indicating first-monolayer uniqueness, the absorption bands for adsorbed H(2)O show intensity saturation and line narrowing with completion of one monolayer. Formation of the ordered H(2)O monolayer likely arises from H bonding to a quasicrystalline surface OH network.


[Factors affecting initial virologic response and emergence of resistant mutants after adefovir treatment in lamivudine-resistant chronic hepatitis B patients].
Adefovir dipivoxil (adefovir) effectively inhibits both wild-type and lamivudine-resistant hepatitis B virus (HBV) replication. The development of adefovir resistance is both delayed and infrequent compared with lamivudine resistance. The aim of this study was to characterize the serologic, biochemical, and virologic response to adefovir, and to explore the factors affecting initial virologic response (IVR, defined as a decrease in serum HBV below 4 log10copies/mL after 6 month of treatment) and adefovir resistance in lamivudine resistant HBV-infected patients. This study population comprised 76 patients with lamivudine-resistance who had received adefovir for more than 12 months between March 2004 and December 2006. The adefovir-resistant mutant was assayed at 6 months and 12 months during adefovir administration. Restriction-fragment mass polymorphism analysis was used for detecting YMDD and adefovir mutants. After adefovir administration, an IVR was observed in 31% of the patients with lamivudine resistance. Factors associated with an IVR were HBeAg negativity (P=0.04) and the presence of liver cirrhosis (P=0.04). Age, sex, pretreatment levels of alanine aminotransferase and aspartate aminotransferase, pretreatment HBV DNA levels, presence of precore mutation, and type of YMDD mutants were not related to an IVR during adefovir treatment. The prevalence of adefovir resistance was 5% and 13% at 6 months and 12 months after therapy, respectively. Mixed infection of the precore mutant was a risk factors for the emergence of adefovir resistance (P=0.01). Lamivudine-resistant HBV patients exhibiting HBeAg negativity and liver cirrhosis were more likely to achieve an IVR after adefovir therapy. Adefovir resistance was associated with mixed infection of the precore mutant.


Unusual causes of hypokalaemia and paralysis.
We demonstrate how the application of physiological principles may help to identify unusual causes of a very low plasma potassium (K+) concentration (P(K)) and paralysis. In the two patients described, the short time course of the illness suggested that there was an acute shift of K+ into cells. The combination of a low rate of excretion of K+, the absence of a metabolic acid-base disorder, and the fact that the clinical findings occurred very soon after a large intake of carbohydrate supported this impression. Surprisingly, the P(K) remained low for many hours after these stimuli to shift K+ into cells had abated. The missing link in this story was eventually provided by the attending medical team with the help of their mentor, Professor McCance.


Effects of ginkgo biloba on testicle injury induced by diethylstilbestrol in mice.
To evaluate the effect of gingko biloba (EGb) on diethylstilbestrol (DES) induced testicle injury in mice. Fifty male mice were divided into a control group (A), DES group (B), and 3 EGb groups (C, D, E). The EGb-treated groups received peritoneal EGb at 8.75 (C), 17.5 (D), 35 mg/kg (E) BW daily for 7 days. The control group was given equivalent amount of normal saline. The mice in groups B, C, D and E were injected hypodermically with DES at 40 mg/kg BW daily 4 hours after the first herbal administration, while the control was given olive oil. Compared with DES group, the testis coefficients-relative testicular weight increased in the three EGb-treated groups. No significant difference was observed in epididymis coefficients. Lipid peroxidation status and antioxidant enzyme activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were significantly elevated in testes of EGb-treated groups. Lactate dehydrogenase (LDH) activities and malonaldehyde (MDA) contents were significantly decreased in testes of the EGb groups. The results indicate that EGb protects the testis from diethylstilbestrol-induced injury.


Impairment of hypoxia-induced HIF-1α signaling in keratinocytes and fibroblasts by sulfur mustard is counteracted by a selective PHD-2 inhibitor.
Skin exposure to sulfur mustard (SM) provokes long-term complications in wound healing. Similar to chronic wounds, SM-induced skin lesions are associated with low levels of oxygen in the wound tissue. Normally, skin cells respond to hypoxia by stabilization of the transcription factor hypoxia-inducible factor 1 alpha (HIF-1α). HIF-1α modulates expression of genes including VEGFA, BNIP3, and MMP2 that control processes such as angiogenesis, growth, and extracellular proteolysis essential for proper wound healing. The results of our studies revealed that exposure of primary normal human epidermal keratinocytes (NHEK) and primary normal human dermal fibroblasts (NHDF) to SM significantly impaired hypoxia-induced HIF-1α stabilization and target gene expression in these cells. Addition of a selective inhibitor of the oxygen-sensitive prolyl hydroxylase domain-containing protein 2 (PHD-2), IOX2, fully recovered HIF-1α stability, nuclear translocation, and target gene expression in NHEK and NHDF. Moreover, functional studies using a scratch wound assay demonstrated that the application of IOX2 efficiently counteracted SM-mediated deficiencies in monolayer regeneration under hypoxic conditions in NHEK and NHDF. Our findings describe a pathomechanism by which SM negatively affects hypoxia-stimulated HIF-1α signaling in keratinocytes and fibroblasts and thus possibly contributes to delayed wound healing in SM-injured patients that could be treated with PHD-2 inhibitors.


Choroidal melanocytes and associated pathology.
The embryologic origins of choroidal and cutanoeus melanocytes, also of the genes involved in cutaneous and choroidal melanoma, are identical, even the two kinds of tumors are different entities. This is a general scientific report, which stretches the molecular mechanisms, as basement of choroidal melanocytes proliferation.


The use of macrophages stimulated by immune interferon as indicator cells in the mononuclear phagocyte assay.
Macrophages obtained from human monocytes by monolayer culture were stimulated with recombinant immune interferon. They were compared with unstimulated macrophages and monocytes as indicator cells in the mononuclear phagocyte assay, using both IgG anti-Rh(D)-coated complement-coated red cells. The presence of the interferon in the culture medium improved the adherence of macrophages in monolayers. The interferon markedly augmented the number of IgG-coated red cells which became attached to the macrophages and reduced the amount of antibody needed for red cell-macrophage interaction. This stimulatory effect occurred regardless of the IgG subclass composition of the anti-Rh(D) antibody. The activity of the stimulated macrophages to interact with IgG- or complement-coated red cells was considerably greater than that of monocytes. The results imply that macrophages treated with recombinant immune interferon are more sensitive than monocytes as indicator cells in the mononuclear phagocyte assay.


Image of a left atrial mass after a cardiopulmonary bypass in a child.
Invagination of an appendage into the left atrium is a rare complication. It occurs spontaneously or after open-heart surgery. In our case, a postoperative transesophageal echocardiogram, after closure of a ventricular septal defect in a 5-month-old infant, revealed a large mass in the left atrium. A diagnosis of a left appendage inversion was confirmed after external examination of the heart. Herein, we provide echocardiographic images before, during, and after manual reversion of the left appendage. Misdiagnosis of this complication could have led to an additional unnecessary surgical procedure that could have impacted on the patient's morbidity.


Comparison of patient age with MR imaging features of gangliogliomas.
The purpose of this study was to compare MR imaging features of gangliogliomas in children less than 10 years old with those seen in patients at least 10 years old. Our study population consisted of 15 female patients and 10 male patients with a mean age of 20 years. The early childhood group was composed of six children with a mean age of 5.5 years. The older group was composed of 19 patients with a mean age of 25.6 years. We assessed tumor volume, tumor location, percentage of tumor that was cystic, pattern of contrast enhancement, and degree of edema. The temporal lobe was the most common tumor location in both groups. Mean tumor volume in the early childhood group was 83 cm3, which was significantly larger than the mean tumor volume (9.78 cm3) for the older group (p = 0.001). Cystic tumors were more common in the early childhood group (83%) than in the older group (63%), and the average percentage of cysts in the cystic tumors was much higher in the early childhood group (67%) than in the older group (30%). Contrast enhancement was seen in five of six early childhood tumors and 13 of 16 tumors in older patients. Four of six tumors in the early childhood group and five of 19 tumors in the older patient group had associated edema. The mean tumor volume of gangliogliomas in the early childhood group was significantly larger than that of the older patient group. This finding may be indicative of differences in tumor growth patterns in the two groups, ability of the hemicranium to adjust to mass effect in childhood, or sampling error as a result of a relatively small sample size.


Intimacy needs and chronic illness: strategies for sexual counseling and self-management.
Individuals experiencing a chronic illness have many needs and concerns. One area frequently overlooked is that of intimacy. Those experiencing cardiovascular illnesses have concerns about the strain of sexual activity on their heart. Individuals with lung diseases may perceive that sexual activity is no longer possible because of breathing difficulties. Accurate information and strategies for self-management are needed to address the intimacy needs and concerns of these individuals. The purpose of this article is to identify intimacy needs and strategies for sexual counseling for individuals with cardiovascular illnesses such as myocardial infarction, heart failure, implantable defibrillators, hypertension, and for chronic lung problems.


Lectins for histochemical demonstration of glycans.
Lectins have been proven to be invaluable reagents for the histochemical detection of glycans in cells and tissues by light and electron microscopy. This technical review deals with the conditions of tissue fixation and embedding for lectin labeling, as well as various markers and related labeling techniques. Furthermore, protocols for lectin labeling of sections from paraffin and resin-embedded tissues are detailed together with various controls to demonstrate the specificity of the labeling by lectins.


Characterization of human serum amyloid A protein isoforms separated by two-dimensional electrophoresis by liquid chromatography/electrospray ionization tandem mass spectrometry.
A detailed structural analysis of the serum amyloid A proteins (SAA) of an individual with highly active, chronic rheumatoid arthritis is reported. SAA isoforms were separated by high-resolution two dimensional (2-D) gel electrophoresis. Peptide mapping by reverse-phase chromatography/electrospray ionization tandem mass spectrometry was applied to correlate the protein(s) contained in each spot with their respective coding gene and to study the post-translational processing and modification events which might result in differential electrophoretic mobility. Nine protein spots were analyzed. The six major spots corresponded to the Arg and des-Arg forms of SAA1 alpha and SAA2 alpha, respectively, and to the glycosylated and nonglycosylated form of constitutive serum amyloid A protein (C-SAA). Two minor spots were identified as SAA1 alpha isoforms containing post-translational modifications. We suggest that these variants contained a gamma-N, N'-dimethylasparagine residue at position 83 and that one of them was additionally oxidized at Trp53 and Trp85. The ninth spot was shown to contain a mixture of SAA1 alpha and SAA2 alpha. To our knowledge, this is the first report in which analysis of peptides has been used to verify the presence of C-SAA in acute-phase serum. Furthermore, the data illustrate that extensive post-translational processing results in a structurally diverse class of acute-phase SAA proteins, which are derived from a small number of genes. Finally, the fast and conclusive technology used in this study promises to be generally useful for the comprehensive investigation of proteins at the level of the primary structure.


Dystonia following head trauma: a report of nine patients and review of the literature.
We report nine patients who developed dystonia following head trauma. The most frequent form was hemidystonia only (six patients). One patient presented with hemidystonia plus torticollis, one with bilateral hemidystonia and one with torticollis only. Seven patients sustained a severe head injury, and two had a mild head injury. At the time of injury, six were younger than 10 years, two were adolescents, and the patient with torticollis only was an adult. Except in the patient with torticollis only, the onset of dystonia varied considerably from months to years. All patients with hemidystonia had posthemiplegic dystonia of delayed onset. Seven out of 8 patients with hemidystonia had lesions involving the contralateral caudate or putamen, as demonstrated by CT and MR. The patient with hemidystonia plus torticollis had no lesion to the basal ganglia, but a contralateral pontomesencephalic lesion. Response to medical treatment was generally poor. Functional stereotactic operations were performed in seven patients. A variety of factors may be responsible for the vascular or nonvascular posttraumatic basal ganglia lesions, which may lead to dystonia. The pathophysiology seems to be more complex than thought previously. We believe that dystonia following head injury is not as rare as is assumed. Awareness of its characteristics and optimized diagnostic procedures will lead to wider recognition of this entity.


Angina bullosa haemorrhagica: presentation of eight new cases and a review of the literature.
Angina bullosa haemorrhagica (ABH) describes the acute and sometimes painful onset of oral blood-filled vesicles and bullae not attributable to blood dyscrasia, vesiculo-bullous disorders, systemic diseases or other known causes. The haemorrhagic bullae spontaneously burst after a short time resulting in ragged, often painless, superficial erosions that heal spontaneously within 1 week without scarring. Although the pathogenesis is still unclear, ABH seems to be a multifactorial phenomenon: dental or functional trauma seems to be the major provoking factor. The lesions of ABH can be easily confused with other mucosal diseases. It is important that the presentation of this benign disorder is distinguished from other more serious disorders with similar presenting features. The aim of this paper is to report the clinical features of eight cases of ABH, in an attempt to distinguish ABH from other blistering diseases of oral mucosa and to describe their management.


Poly(ADP-ribose) polymerase-1 promotes microglial activation, proliferation, and matrix metalloproteinase-9-mediated neuron death.
Activated microglia contribute to cell death in ischemic and neurodegenerative disorders of the CNS. Microglial activation is regulated in part by NF-kappaB, and the nuclear enzyme poly(ADP-ribose) polymerase-1 (PARP-1) enhances NF-kappaB binding to DNA. In this study, the role of PARP-1 in microglia-mediated neurotoxicity was assessed using microglia from wild-type (wt) and PARP-1-/- mice. Cultured microglia were incubated with TNF-alpha, a cytokine that is up-regulated in many neurological disorders. When stimulated with TNF-alpha, wt microglia proliferated, underwent morphological changes characteristic of activation, and killed neurons placed in coculture. The effects of TNF-alpha were markedly attenuated both in PARP-1-/- microglia and in wt microglia treated with the PARP enzymatic inhibitor 3,4-dihydro-5-[4-(1-piperidinyl)butoxy]-1(2h)-isoquinolinone. These effects were also blocked by (E)-3-(4-methylphenylsulfonyl)-2-propenenenitrile, which inhibits translocation of NF-kappaB to the nucleus. TNF-alpha also up-regulated microglial release of matrix metalloproteinase-9 (MMP-9), an enzyme with potential neurotoxic properties that is transcriptionally regulated by NF-kappaB. This up-regulation was blocked in PARP-1-/- microglia and in wt microglia by the PARP inhibitor 3,4-dihydro-5-[4-(1-piperidinyl)butoxy]-1(2h)-isoquinolinone. Microglia from MMP-9-/- mice were used to evaluate the contribution of MMP-9 to microglial neurotoxicity. MMP-9-/- microglia treated with TNF-alpha showed substantially reduced neurotoxicity relative to the wt microglia. TNF-alpha-stimulated wt microglia treated with the MMP inhibitor ilomastat also showed reduced neurotoxicity. These findings suggest that PARP-1 activation is required for both TNF-alpha-induced microglial activation and the neurotoxicity resulting from TNF-alpha-induced MMP-9 release.


The Discriminative stimulus effects of gamma-hydroxybutyrate and related compounds in rats discriminating baclofen or diazepam: The role of GABA(B) and GABA(A) receptors.
The discriminative stimulus effects of gamma-hydroxybutyrate (GHB) can be mimicked by GABA(A) receptor-positive modulators (e.g., diazepam) and GABA(B) receptor agonists (e.g., baclofen). The purposes of this study were to see whether stimulus control could be established with baclofen and to further characterize the role of GABAergic mechanisms in the behavioral actions of GHB by evaluating GHB and related compounds in rats discriminating either diazepam or baclofen. Training criteria were satisfied with baclofen and diazepam after 69 and 44 sessions, respectively. GHB and its precursors gamma-butyrolactone and 1,4-butanediol occasioned >80% responding on the drug-associated lever in rats discriminating baclofen and <11% in rats discriminating diazepam. Diazepam and other GABA(A) receptor-positive modulators occasioned intermediate levels of responding on the baclofen lever, whereas baclofen occasioned less than 4% responding on the diazepam lever. The GABA(B) receptor antagonist CGP 35348 [(3-aminopropyl)(diethoxymethyl) phosphinic acid] partially antagonized the effects of baclofen as well as the baclofen-like effects of GHB, and flumazenil partially antagonized the effects of diazepam. This study established stimulus control with baclofen, and substitution data provided direct evidence for a role of GABAergic, especially GABA(B), mechanisms in the discriminative stimulus effects of GHB. The lack of substitution by GHB or its metabolic precursors for diazepam indicates a comparatively smaller role of GABA(A) mechanisms in these effects of GHB. The inability of CGP 35348 to completely attenuate the effects of baclofen and GHB suggests that multiple receptors could be involved in the discriminative stimulus effects of GHB.


Canadian cancer statistics 1990.
In 1990, an estimated 104,000 new cases of cancer (excluding non-melanoma skin cancer) will be diagnosed in Canada. The estimated number of deaths due to cancer in that same year will total 54,500. Just over one in three Canadians can expect to develop some form of cancer during their lifetime, and one in four men and one in five women will die from this disease. Almost 10% of women will develop breast cancer, while close to 8% of men will develop lung cancer. In 1990, lung cancer alone is expected to account for 17,300 newly diagnosed cancers (16.6% of the total), and 14,200 cancer deaths (26% of the total). Cancer will also take its toll as the fourth leading cause of death in children. This article explores additional statistics, trends in cancer incidence and mortality since 1970, cancer survival rates, and cancer mortality by income level. This article is based on material prepared by Statistics Canada for inclusion in Canadian Cancer Statistics 1990 (1), and developed in collaboration with the Canadian Cancer Society, Health and Welfare Canada, and provincial and territorial cancer registries.


Overcoming the odds: access to care for immigrant children in working poor families in California.
To explore the extent to which, among working poor families, uninsured immigrant children experience more barriers to care than uninsured nonimmigrants, and compare these differences to those of insured children. We used data from the 2001 California Health Interview Survey, a randomized, population-based telephone survey conducted from November 2000 through September 2001. Financial and nonfinancial access to health care and utilization of health services were examined for 3,978 nonimmigrant and 462 immigrant children and adolescents under the age of 18 years. We compared differences in crude rates across four subgroups (insured immigrants, uninsured immigrants, insured nonimmigrants, uninsured nonimmigrants) and in adjusted models controlling for socioeconomic and immigration characteristics, parental language, health status, and other demographic factors. More immigrant than nonimmigrant children lacked health insurance at the time of the interview (44% vs. 17%, p < 0.0001). Among the uninsured, immigrants had higher odds of perceiving discrimination (11% vs. 5%, p < 0.05) and postponing emergency room (ER) (16% vs. 7%, p < 0.05) and dental care (40% vs. 30%, p < 0.05) after controlling for covariates. Among the insured, immigrants fared worse on almost every access and utilization outcome. Among insured immigrants, child and parent undocumented status and having a non-English-speaking parent contributed to missed physician and ER visits. Disparities in access and use remain for immigrant poor children despite public insurance eligibility expansions. Insurance does not guarantee equitable health care access and use for undocumented children. Financial and nonfinancial barriers to health care for immigrant children must be removed if we are to address disparities among minority children.


Proton pump inhibitor usage and the associated risk of pneumonia in patients with chronic kidney disease.
Chronic kidney disease (CKD) is a serious medical problem and public health issue in Taiwan. Gastrointestinal symptoms frequently occur in patients with CKD, and proton pump inhibitors (PPIs) have therapeutic indications for gastrointestinal disorders involving excessive acid production. However, PPIs may also increase the risk of developing pneumonia through acute and irreversible gastric acid suppression. This study aimed to characterize differences in the risk of pneumonia in patients with CKD who use PPIs. This population-based case-control cohort study in Taiwan collected data from the Taiwan Health Insurance Research Database. Cases studied consisted of all patients in the database with an initial diagnosis of CKD during the 5-year period from 1997 to 2002. Each patient with CKD who used PPIs during this 5-year period was tracked to identify the occurrence of any type of pneumonia. We estimated the adjusted hazard ratios (HRs) and 95% confidence interval (95% CI) by using multiple logistic regression analysis. The adjusted HR of the risk of pneumonia for patients with CKD using PPIs was 2.21 (95% CI = 1.59-3.07, p < 0.001). The risk of pneumonia was found to be positively associated with administration of PPIs. We observed a greater risk of pneumonia in patients with CKD using PPIs than in patients not using PPIs. Results of this study suggest that use of PPIs in CKD patients may be associated with increasing the risk of pneumonia. Physicians should exercise caution while prescribing PPIs for patients with CKD.


Epikeratophakia for treatment of keratoconus.
Epikeratophakia has been applied for the correction of aphakia in children and adults as well as for the treatment of keratoconus to correct the refractive errors accompanied by these conditions. In this paper we present preliminary results of the outcome of ten consecutive keratoconus patients who were subjected to epikeratophakia. The patients suffered from advanced keratoconus without any major haziness in the optic area of the cornea, and they had become unable to tolerate contact lenses. Follow-up period varied form 1 to 4 months. Two minor complications were verified (one erosion and one partly detached lenticule) but these were managed and further healing was without problems. The keratometry values were markedly changed by the operation. The improval of the visual acuity after the operation was accompanied by the postoperative increase in the transparency of the lenticule. Epikeratophakia seems to be a safe and relatively simple method for the treatment of keratoconus.


Parathyroid hormone increases epidermal growth factor receptors in cultured human trophoblastic cells from early and term placenta.
The effect of PTH on the epidermal growth factor (EGF) receptor was analyzed during the in vitro differentiation of human cytotrophoblasts. The cytotrophoblasts were isolated by a trypsin-DNase method from first trimester and term placentas and purified on a Percoll gradient. In culture, these cells aggregated and fused together to form a syncytium. This in vitro differentiation was associated with a 2-fold increase in 125I-EGF binding after 48 h of culture. The addition of 0.1 microM PTH (PTH-treated cells) to the culture medium induced a significant 2- to 3-fold increase (P less than 0.005) in EGF binding. The effect was dose related with a maximum obtained at a 1 nM concentration. Scatchard analyses revealed that PTH-treated cells possess a 2-fold higher number of high affinity sites as compared to control cells from early placenta (0.71 +/- 0.06 pmol/mg protein and 0.34 +/- 0.04 pmol/mg protein, respectively) and from term placenta (1.24 +/- 0.10 pmol/mg protein and 0.61 +/- 0.07 pmol/mg protein, respectively). The apparent Kd values for high affinity sites (0.15 nM) and for low affinity sites (4 nM) were not altered either by the gestational age of the cells or by PTH treatment. With respect to the EGF-dependent phosphorylation in membranes of trophoblast cells in culture, it was found that the phosphorylation of two major proteins of 175 kilodaltons and 35 kilodaltons, is greatly increased in PTH-treated cell membranes in the presence of EGF. This PTH-induced effect on EGF receptors was associated with an augmented functional response of trophoblastic cells to EGF. PTH increased the EGF-stimulated secretion of hCG. These results demonstrate that PTH increases the number of biologically active EGF receptors during the in vitro differentiation of human trophoblast cells. This PTH-induced effect suggests a role for this hormone in the regulation of the growth and the endocrine functions of these cells.


Do patients with haemophilia undergoing cardiac surgery have good surgical outcomes?
A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether patients with haemophilia undergoing cardiac surgery have good surgical outcomes. Haemophilia A and haemophilia B are sex-linked recessive inherited diseases affecting males only, with females acting as carriers. The conditions result in various degrees of factor VIII or factor IX deficiency, respectively. The life expectancy of haemophilia patients is increasing and now approaches that of the general male population, and they are confronted with age-related co-morbidity, including ischaemic cardiovascular disease. Replacement of the deficient factor (VIII for haemophilia A and IX for haemophilia B) is the cornerstone of treatment; other therapeutic options include tranexamic acid, desmopressin and aprotinin. Recently, the advent of recombinant factor VIII and IX has eliminated the infective risk of using factor concentrates, such as prothrombin complex concentrate or fresh frozen plasma. A total of 84 papers were found using the reported search criteria, and out of this 25 papers, selected with reference to a more modern date range, provided the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results were tabulated. We conclude that there is lack of good-quality evidence and that, in all probability, these papers are subject to publication bias as poor outcomes are unlikely to have been reported. However, all the reported series showed that good outcomes are possible in this specific subgroup of patients given the correct approach. The data accrued from these studies (a total of 30 adults and three children) suggest that routine cardiac surgery can be performed safely in patients with haemophilia, with minimal morbidity and mortality. We identified the following key points to achieve this result: a team approach, a factor replacement protocol and perioperative monitoring of factor levels. Intraoperative plasma factor levels can be easily measured before heparin and after protamine sulphate administration, whereas during cardiopulmonary bypass this will require a chromogenic method. Exposure to factor concentrates early in the life might predispose a patient with severe haemophilia to the development of inhibitors. Moreover, the absence of inhibitors should be confirmed before any surgical procedure.


Use of augmented Lagrangians in the calculation of molecular conformations by distance geometry.
Distance geometry is a technique widely used to find atomic coordinates that agree with given upper and lower bounds on the interatomic distances. It is successful because it chooses at random some relatively good "trial coordinates" that take into account the whole molecule and all constraints at once. Customarily, these trial coordinates must be refined by minimizing a penalty function until the structure agrees with the original bounds. Here we present an alternative to minimizing the penalty function, which has the advantage of more precisely satisfying the bounds, showing more clearly when the bounds are mutually contradictory, and simultaneously optimizing an objective function subject to precise satisfaction of the bounds.


Schwann cells in neuroblastoma.
Why should we consider Schwann cells when we are interested in the biology of neuroblastomas (NBs)? Although we are familiar with the term "stroma-rich" NB, we basically think of a favourable prognostic subgroup, histologically distinguished by the development of a prominent Schwann cell-stroma. According to current opinion on the maturation processes in NBs, the NB-associated Schwann cell is believed to represent a differentiation product of the NB cell, and we therefore do not envisage the Schwann cell as having any important role in NBs. However, our interest was raised after having realised that Schwann cells in NBs are normal cells, very likely attracted to the neoplastic neuroblasts. But what role does this cell play in these tumours? Can we still reduce the appearance of Schwann cells in NBs to an epi-phenomenon or is this cell population responsible for the differentiation of certain NBs? If so, will it be possible to use their strategies to induce differentiation of neuroblasts and so render them non-aggressive, mature ganglionic cells? To shed light on the possible interactions between normal Schwann cells and NB cells, the maturation capacity of NBs and the genetic constitution of the two main cell populations in these tumours are briefly reviewed. Some data leading to the current view on the origin of the Schwann cells in NBs, and several physiological aspects of the Schwann cells, including normal neurone-Schwann cell interactions, are detailed.


Multi-body optimization with subject-specific knee models: performance at high knee flexion angles.
When estimating knee kinematics from skin markers and stereophotogrammetry, multi-body optimization (MBO) has provided promising results for reducing soft tissue artefacts (STA), but can still be improved. The goal of this study was to assess the performance of MBO with subject-specific knee models at high knee flexion angles (up to 110°) against knee joint kinematics measured by magnetic resonance imaging. Eight subjects were recruited. MBO with subject-specific knee models was more effective in compensating STA compared to no kinematic and spherical constraints, in particular for joint displacements. Moreover, it seems to be more reliable over large ranges of knee flexion angle. The ranges of root mean square errors for knee rotations/displacements were 3.0°-9.2°/1.3-3.5 mm for subject-specific knee models, 6.8°-8.7°/6.0-12.4 mm without kinematic constraint and 7.1°-9.8°/4.9-12.5 mm for spherical constraints.


The effect of mid-luteal estradiol level on the outcome of ICSI-ET cycles.
We investigated if mid-luteal estradiol levels could predict the outcome in intracytoplasmic sperm injection embryo transfer (ICSI-ET) cycles ( n=231). Pregnant and non-pregnant women were compared regarding their peak estradiol levels on human chorionic gonadotropin (hCG) injection day, and mid-luteal estradiol levels on the 7th day following oocyte recovery. Pregnancy rates of the groups that were designed according to the "peak/mid-luteal estradiol level" and the mid-luteal estradiol levels were also compared. Peak and mid-luteal estradiol levels in pregnant women were higher than in non-pregnant women in all patients, although the difference between peak and mid-luteal estradiol levels were similar in pregnant and non-pregnants. Pregnant women had higher mid-luteal estradiol levels in good responders, but the peak estradiol levels of pregnant and non-pregnant women were similar. In poor responders, pregnant and non-pregnant women were similar with respect to peak and mid-luteal estradiol levels. Both in all patients and good responders, women with mid-luteal estradiol levels <200 pg/ml had lower pregnancy rates than those with >2000 pg/ml. Peak/mid-luteal estradiol ratios of pregnant and non-pregnant women were not significantly different in all patients, good responders and poor responders; although a tendency for a lower ratio in pregnants was encountered in good responders. Pregnancy rates of the groups according to the "peak/mid-luteal estradiol ratio" were similar; in all patients, good responders and poor responders. A relation between the mid-luteal estradiol level and the outcome is encountered only in good responders.


Surgical management of parotid hemangioma.
Hemangiomas represent one of the most common childhood neoplasms. They are often managed conservatively, requiring numerous years for spontaneous involution. No effective medical treatment has been reported for children with large, deforming hemangiomas of the parotid gland and overlying cheek. The authors retrospectively studied 17 children who underwent surgical resection of parotid hemangiomas at Childrens Hospital Los Angeles from 1997 to 2003. All 17 patients had improvements in facial asymmetry and deformity. There were no major complications. Minor complications included hematoma (11.8 percent), transient facial nerve palsy (11.8 percent), and blood transfusion (5.9 percent). All operations were performed on an outpatient basis. Surgical resection of parotid hemangiomas provides an aesthetic benefit to young children with low associated morbidity. Early resection by an experienced surgeon should be considered as a treatment option for these disfiguring lesions.


Interaction of serum and colony-stimulating factor for survival of a factor-dependent hemopoietic progenitor cell line.
The growth in vitro of the murine myeloid cell line FDC-P1 depends on the presence of serum and a murine hemopoietic growth factor (either granulocyte/macrophage colony-stimulating factor (GM-CSF) or multipotential colony-stimulating factor (multi-CSF, IL3]. To determine the differential roles of serum and colony-stimulating factor (CSF) during the growth of FDC-P1 cultures, we investigated the kinetics of proliferation and death after withdrawal of serum or CSF, using flow cytometry to quantitate the numbers of vital and dead cells. After withdrawal of CSF, the cells died without entering a quiescent state. The life span of cultures lacking CSF increased with increasing concentrations of serum (greater than 50 h at 30% serum), and the cells kept dividing until they died. During the period of population death caused by the absence of CSF, the re-addition of CSF immediately prevented further cells from dying. After the withdrawal of serum in the presence of CSF, the cells continued to live and proliferate for weeks, but required high cell densities (much greater than 10(5)/ml), which suggests that the cells produced an active substance that can substitute for serum. Serum as well as serum-free conditioned medium from dense cultures made the survival and growth of FDC-P1 cultures independent of cell density. Without sufficient quantities of this activity, all cells of the population died within an interval that was much shorter than one cell cycle, which indicates that the factor acts throughout most of the cell cycle. The results suggest that both the CSF and the serum factor act together to permit cell survival, rather than to drive proliferation.


Clinical characteristics of high-grade lymphomas with immune genes in germline configuration.
In a prospective study of 42 high-grade lymphomas which were categorized according to the Kiel classification, the clinical significance of immune genotyping was studied. Immunoglobulin (Ig) and T-cell receptor (TCR) gene rearrangements were investigated. In 33 cases the immune genotype confirmed the phenotype. In one case with equivocal phenotype a TCR beta-chain rearrangement proved the T-cell origin of the lymphoma. None of the cases showed a bigenotype. There were eight lymphomas with immunoglobulin and TCR beta-chain and gamma-chain genes in germline configuration, which were divided into a group of immature lymphomas and a group of lymphomas with a more mature phenotype. The immature lymphomas had widespread disease, rapid progression, and favorable prognosis after intensive chemotherapy. The group of T-cell and Ki-1 lymphomas with null-cell genotype was clinically heterogeneous. Three of four cases were secondary lymphomas after lymphomatoid papulosis, lymphomatoid granulomatosis, or Hodgkin's disease. All cases presented with extranodal involvement. Only one of these patients is in continuous remission. In conclusion, the lack of immunoglobulin and TCR beta-chain and gamma-chain gene rearrangements does not exclude the diagnosis of high-grade malignant lymphoma, especially in cases with unusual extranodal involvement. However, the DNA analysis identifies a null-cell genotype subset of high-grade lymphomas which may have clinical significance.


(2S,8Z)-2-butyroxy-8-heptadecene: major component of the sex pheromone of chrysanthemum gall midge, Rhopalomyia longicauda.
The sex pheromone of the chrysanthemum gall midge, Rhopalomyia longicauda (Diptera: Cecidomyiidae), the most important insect pest in commercial plantations of chrysanthemum, Dendranthema morifolium (Ramat.) Tzvel., in China, was identified, synthesized, and field-tested. Volatile chemicals from virgin females and males were collected on Porapak in China and sent to the United Kingdom for analysis. Coupled gas chromatographic-electroantennographic detection (GC-EAG) analysis of volatile collections from females revealed two compounds that elicited responses from antennae of males. These compounds were not present in collections from males. The major EAG-active compound was identified as 2-butyroxy-8-heptadecene by gas chromatographic (GC) retention indices, mass spectra, in both electron impact and chemical ionization modes, hydrogenation, epoxidation, and derivatization with dimethyldisulfide. The lesser EAG-active compound was identified as the corresponding alcohol. The ratio of butyrate to alcohol in the collections was 1:0.26. Racemic (Z)-8-heptadecen-2-ol and the corresponding butyrate ester were synthesized from (Z)-7-hexadecenyl acetate, and the synthetic compounds found to have identical GC retention indices and mass spectra to those of the natural, female-specific components. Analysis of the volatile collections on an enantioselective cyclodextrin GC column showed the natural pheromone contained (2S,8Z)-2-butyroxy-8-heptadecene. Field tests showed that rubber septa containing racemic (Z)-2-butyroxy-8-heptadecene were attractive to R. longicauda males. The (naturally occurring) S-enantiomer was equally as attractive as the racemate, while the R-enantiomer was not attractive to males, and did not inhibit the activity of the S-enantiomer. The attractiveness of the butyrate was significantly reduced by the presence of even small amounts of the corresponding alcohol.