Plaque pH recovery by mouth-rinses with water.
A transistor pH electrode (pH-ISFET electrode) was placed in each of four human mouths and bacteria were allowed to accumulate on it for 1, 2 or 3 days. Changes of plaque pH were measured in situ after application of sucrose solution (0.1, 1 or 3%) and, then, quick pH recovery by mouth-rinses with water was estimated. Although the acidic pH after application of 0.1% sucrose was easily and quickly recovered from by a few mouth-rinses with water, rather frequent mouth-rinses with water were required to recover from the acidic pH of 2- or 3-day-old plaque after the application of a 1 or 3% sucrose solution. For example, 15 (mean, n = 4) mouth-rinses with water were required for the 3 day-old plaque pH to recover after the application of 3% sucrose solution.


[Integrated treatment of the symptoms of narcolepsy-cataplexy syndrome with sodium oxybate].
Treatment of narcolepsy-cataplexy is based on the use of different drugs that either stimulate or modify REM sleep, which makes it possible to improve the symptoms that characterise the disease. To present the characteristics of sodium oxybate, a new drug that has been approved in the United States and in the European Union for use in treating narcolepsy-cataplexy; the main contribution made by this new agent is the possibility of acting on all the symptoms of the disease at the same time. In four randomised, double-blind, placebo-controlled studies and with a class A level of evidence, sodium oxybate has proved to be effective in improving the cardinal symptoms of narcolepsy-cataplexy, that is to say, hypersomnia, cataplexy and fragmentation of nocturnal sleep. Treatment was well tolerated and the side effects, consisting mainly of nausea or symptoms related with the nervous system, such as anxiety, depression, confusion or drowsiness, were mild or moderate in most cases and rarely led to the patient's giving up the treatment. The drug has a favourable pharmacokinetic profile, with little potential to interact with other pharmaceuticals. It seems to have a synergic effect with modafinil, boosting its effects in the treatment of excessive sleepiness. Although it is a substance that has been used as a recreational drug, no cases of addiction or drug abuse have been observed in narcoleptic patients treated in a controlled manner. Sodium oxybate can be considered to be a first-choice drug in the treatment of narcolepsy-cataplexy.


Vascular endothelial oxidative stress in alcohol-induced hypertension.
Epidemiological studies in humans and experimental studies in animals have shown the link between chronic alcohol consumption and the prevalence of hypertension. However, molecular mechanisms implicated with alcohol-induced increases in blood pressure (BP) remain elusive. The objective of this study was to investigate the relationship between BP and molecular as well as physiological changes in aortic endothelium in chronic ethanol treated rats. Male Fisher rats were given 20% ethanol (4 g/kg) orally and controls received 5% sucrose daily for 12 weeks. The BP was recorded weekly by tail-cuff method and after 12 weeks, rats were anesthetized with pentobarbital, thoracic aorta isolated and used for aortic reactivity using tissue bath and for biochemical analysis. The data show that ethanol ingestion significantly increased systolic, diastolic and mean BP after 12 weeks compared to control. The endothelial nitric oxide synthase (eNOS) and vascular endothelial growth factor (VEGF) expressions were down-regulated leading to depletion of aortic NO levels in ethanol treated rats compared to control. The aortic NADPH oxidase activity significantly enhanced with a concomitant increase in membrane lipid peroxidation and depressed ratio of reduced to oxidized glutathione in alcohol-treated rats compared to control. The aortic vasoconstriction was slightly enhanced in response to phenylephrine but vasorelaxation was significantly diminished in response to acetylcholine, adenosine and sodium nitroprusside in chronic ethanol treated rats. It is concluded that chronic ethanol ingestion induces aortic endothelial oxidative injury and the down regulation of nitric oxide generating system leading to impaired vasorelaxation and hypertension in rats.


Revised estimates of the maternal age specific live birth prevalence of Down's syndrome.
To revise the estimates of maternal age specific live birth prevalence of Down's syndrome in the absence of antenatal screening and selective termination using newly available data. Data were used from the National Down Syndrome Cytogenetic Register (NDSCR), which contains information on nearly all antenatally or postnatally diagnosed cases of Down's syndrome in which a karyotype was confirmed between 1989 and 1998 in England and Wales. It is the largest single series of data on the prevalence of Down's syndrome. The prevalence does not continue increasing at an increasing rate with age above age 45 as has been previously assumed. Above this age the rate of increase declines with increasing age. The overall age pattern is sigmoidal. A new logit logistic model is proposed which fits the data well. The risk of a Down's syndrome live birth is given by: risk=1/(1+exp(7.330-4.211/(1+exp(-0.282x(age-37.23))))).


Use of Multiple Informants to Identify Children at High Risk for ADHD in Turkish School-Age Children.
To examine the distribution of parent- and teacher-rated ADHD symptoms in a Turkish community sample to identify children at high risk for ADHD and to explore the psychosocial correlates of these high-risk children. An 18-item SNAP-IV (Swanson, Nolan, and Pelham) and a three-item impairment scale were completed by parents and teachers on 3,110 children between 7 and 14 years of age from three public schools in Istanbul. Using various case definitions for ADHD, we observed a range of prevalence estimates based on parent (2.7%-9.6%) and teacher (2%-10.1%) reports. Teacher-identified ADHD was associated with low family income and low parental education; parent-identified ADHD was associated with perceived need for mental health treatment. Statistically driven threshold on a symptom scale may overestimate the rate of high-risk children. Relying on one informant is likely to miss some children at high risk. As in clinical practice, therefore, data from multiple informants and evidence of impairment are essential for identifying ADHD.


Conformational investigation of alpha, beta-dehydropeptides. Part III. Molecular and crystal structure of acetyl-L-prolyl-alpha, beta-dehydrovaline methylamide.
The crystal structure of Ac-Pro-delta Val-NHCH3 was examined to determine the influence of the alpha,beta-dehydrovaline residue on the nature of peptide conformation. The peptide crystallizes from methanol-diethyl ether solution at 4 degrees in needle-shaped form in orthorhombic space group P2(1)2(1)2(1) with a = 11.384(2) A, b = 13.277(2) A, c = 9.942(1) A, V = 1502.7(4) A3, Z = 4, Dm = 1.17 g.cm-3 and Dc = 1.18 g.cm-3. The structure was solved by direct methods using SHELXS-86 and refined to an R value of 0.057 for 1922 observed reflections. The peptide is found to adopt a beta-bend between the type I and the type III conformation with phi 1 = -68.3(4) degrees, psi 1 = -20.1(4) degrees, phi 2 = -73.5(4) degrees and psi 2 = -14.1(4) degrees. An intramolecular hydrogen bond between the carbonyl oxygen of ith residue and the NH of (i + 3)th residue stabilizes the beta-bend. An additional intermolecular N...O hydrogen bond joins molecules into infinite chains. In the literature described crystal structures of peptides having a single alpha,beta-dehydroamino acid residue in the (i + 2) position and forming a beta-bend reveal a type II conformation.


Isolation and purification of flavonoid glucosides from Radix Astragali by high-speed counter-current chromatography.
High-speed counter-current chromatography methods, combined with resin chromatography were applied to the separation and purification of flavonoid glycosides from the Chinese medicinal herb, Radix Astragali. Five flavonoid glycosides, namely calycosin-7-O-beta-d-glucoside, ononin, (6aR, 11aR)-9,10-dimethoxypterocarpan-3-O-beta-d-glucoside, (3R)-2'-hydroxy-3',4'-dimethoxyisoflavan-7-O-beta-d-glucoside and calycosin-7-O-beta-d-glucoside-6''-O-acetate, were obtained. Among them, calycosin-7-O-beta-d-glucoside-6''-O-acetate was preparatively separated from Radix Astragali for the first time. Their structures were identified by ESI-MS, (1)H NMR, (13)C NMR, and 2D NMR.


Immigration and health.
The purpose of this integrated review was to examine research on the relationships between immigration and health. The review was limited to studies of immigration into North America published since 1994. The results suggested that, although recent research has furthered the understanding of immigration and health, the multiple health effects of the various social and cultural processes immigrants undergo are still not clearly understood. In addition, research on acculturation has not clarified the positive or negative effects of acculturation on health. The incorporation of transnational perspectives and contemporary concepts and frameworks such as biculturalism, undocumentedness, and transitions was noted as a significant contribution from recent research. The results of this integrative review indicate that interdisciplinary research on immigration and health is moving in new directions. The reviewers provide suggestions for future research on health disparities as well as on possible health protective factors among diverse immigrant populations.


Establishing a consultation-liaison psychiatry clinical database in an Australian general hospital.
This paper describes the institution of a clinical database in the consultation-liaison psychiatry service of an Australian general hospital psychiatry unit. One of the problems faced was that many researchers and clinicians in Australia use the ICD-9 rather than the DSM-III-R classification system. Nevertheless, it was possible to use the DSM-III-R-based MICRO-CARES clinical database management system in this project. The data obtained during the first 12 months of its use are presented. Despite differences in the patient demographic characteristics, the data obtained are within the ranges described for North American and European sites. The local benefits of such a clinical database are described, and it is argued that such a database is also necessary for interhospital and international collaborative studies and comparisons.


Vitrectomy lens for examination of the optic disk in young children with glaucoma.
To examine the optic disk in infants and young children with glaucoma after the administration of anesthesia, a lens designed for vitrectomy surgery was used to obtain magnified stereoscopic images of the optic disk. Excellent visualization of the optic disk was obtained with our method. Comparison of optic disk appearance is facilitated by using an inexpensive lens designed for vitrectomy surgery.


[Transition from the depressive stage to the manic stage during the treatment with antidepressive drugs].
The effects of antidepressant drugs on phase switching was studied in 602 individuals treated for endogenous depression. Altogether 869 depressed phases were evaluated retrospectively--there were 470 depressed phases in the course of bipolar affective disorder and 399 of unipolar disorder or with the undefined course. Switching from depression to mania was observed in patients with bipolar disorder--in 27.9% of cases of bipolar depression and in 21.5% of bipolar patients. Most frequently the switching was observed during management of depressed phase with amitriptyline (24.4% of treatments with this drug). The results point to a role of cholinergic system in pathophysiology of switching out of depression into mania during treatment with antidepressant drug.


Anti-high-mobility group box chromosomal protein 1 antibodies improve survival of rats with sepsis.
High-mobility group box chromosomal protein 1 (HMGB1) has recently been shown to be an important late mediator of endotoxin shock, intraabdominal sepsis, and acute lung injury, and a promising therapeutic target of severe sepsis. We sought to investigate the effect of antibodies to HMGB1 on severe sepsis in a rat cecal ligation and puncture (CLP) model. Adult male Sprague-Dawley rats underwent CLP and then were randomly divided into two groups: treatment with anti-HMGB1 polyclonal antibodies, and non-immune IgG-treated controls. The serum HMGB1 concentrations were measured at ten time points (preoperatively, and postoperatively at 4, 8, 20, 32, and 48 h and at 3, 4, 5, and 6 days). Hematoxylin-eosin staining, elastica-Masson staining, and immunohistochemical staining for HMGB1 were performed on the cecum and the lung to assess pathological changes 24 h after the CLP procedure. Treatment with anti-HMGB1 antibodies significantly increased survival [55% (anti-HMGB1) vs. 9% (controls); P< 0.01]. The serum HMGB1 concentrations at postoperative hours 20 and 32 of the anti-HMGB1 antibody-treated animals were significantly lower than those of the controls (P < 0.05). Treatment with anti-HMGB1 antibodies markedly diminished the pathological changes and the number of HMGB1-positive cells in the cecum and the lung. The present study demonstrates that anti-HMGB1 antibodies are effective in the treatment of severe sepsis in a rat model, thereby supporting the relevance of HMGB1 eradication therapy for severe sepsis.


[Intrathecal baclofen in treatment of spasticity casuistry of the Centro Hospitalar de Coimbra].
The neuromotor techniques do not have good results in severe spasticity prevention and treatment (Ashworth Scale > or = 3). High doses of oral Baclofen are required, thus intrathecal baclofen is a current alternative. To assess the effectiveness of treatment, the eight Spinal Cord Injury (SCI) patients with a intrathecal baclofen pump are controlled in a specific consultation in the Rehabilitation Service of C.H.C. The authors analyse the results and made a bibliographic review. Medline research and retrospective study through the analysis of the individual clinical file. Intrathecal baclofen is effective in severe spasticity when oral baclofen is ineffective or when intolerable side effects occur. In our study group of nine patients, one had infection to the material in the Baclofen pump, and in the other eight patients was observed improvement of spasticity: six were re-classified grade 2 and two were re-classified grade 3 (Modified Ashworth Scale). Intrathecal baclofen infusion is an effective therapeutic alternative in severe spasticity due to spinal cord lesions. With this method, adequate liquor concentrations for hyperactivity/hipertonicity reduction are possible without the normal side effects that occur with the high oral dosage (about 100 times higher).


Purification and some properties of a protein obtained from normal human plasma which inhibits the platelet aggregation induced by thrombotic thrombocytopenic purpura plasma.
Plasma from patients with thrombotic thrombocytopenic purpura (TTP) caused the aggregation of washed human platelets, which was inhibited by preincubation with normal plasma. Using salt fractionation, ion exchange chromatography, and preparative agarose gel electrophoresis, we purified a protein from normal plasma which inhibited the platelet aggregation caused by TTP plasma. On SDS polyacrylamide gel, the purified inhibitor gave a single band with a M.W. of 150,000. The antiserum against the purified protein neutralized the activity of the inhibitor and formed an identical precipitin line against normal and TTP plasma.


Peroxisomal disorder-unusual presentation as failure to thrive in early infancy.
Failure to thrive is not uncommon in paediatric practice and often leads to multiple investigations to find the underlying cause. We report an infant who presented mainly with mild dysmorphism, failure to thrive and elevated alanine transferase (ALT) in early infancy. She was diagnosed to have a peroxisomal biogenesis disorder on further investigation. Peroxisomal disorders represent a spectrum of conditions with absent or abnormal function of intra-cytoplasmic organelles called peroxisomes. Clinical presentation is quite varied, depending on both the type and severity. We describe the clinical presentation of this case, followed by a brief discussion on peroxisomal disorders.


[The tendency of applying medicines for the treatment of consumptive thirst in the period of Jin and Yuan dynasties].
In the period of Jin and Yuan dynasties, the system of syndrome differentiation and treatment in traditional Chinese medicine on consumptive thirst became more and more mature and the medication became gradually precise. By statistically analyzing the prescriptions and herbs for the treatment of consumptive thirst in 22 medical works of the Jin and Yuan dynasties, it is concluded that there are 7 categories with 20 kinds of major herbs applied. This kind of tendency of applying the medicines in consumptive thirst embodied the recognition that the syndrome classification and therapeutic methods by doctors of the Jin and Yuan dynasties, and reflected the cognition on the pathogenesis, site of lesions of consumptive thirst.


Effect of a test meal, duodenal acidification, and tetragastrin on the plasma concentration of beta-endorphin-like immunoreactivity in man.
The effects of various test materials on plasma beta-endorphin-like immunoreactivity (beta-EpLI) were investigated in man using a specific radioimmunoassay developed by the authors. Plasma beta-EpLI was determined after extraction by the acid/acetone method (recovery 73 +/- 5%). The intraassay and interassay coefficients of variation were 5.0% and 7.6%, respectively. The plasma concentrations of human beta-EpLI in normal subjects were 11.6 +/- 4.0 pmol/l for men (n = 23) and 10.7 +/- 4.8 pmol/l for women (n = 27). Ingestion of a test meal (150 g of Campbell's condensed meat soup) resulted in a biphasic rise in plasma beta-EpLI from the basal level of 4.4 +/- 1.0 pmol/l to 29.2 +/- 1.9 pmol/l after 5 min and 24.8 +/- 6.7 pmol/l after 90 min. Intraduodenal infusion of 115 ml of 0.1 M HCl over 10 min increased the plasma beta-EpLI level from 8.7 +/- 0.5 pmol/l to 15.5 +/- 0.4 pmol/l at 10 min after the start of infusion, but the level rapidly returned to the initial value after the end of the infusion. Intramuscular injection of 4 micrograms/kg body weight of tetragastrin markedly stimulated gastric acid output and beta-EpLI release, but pretreatment with 10 mg of histamine H2 receptor antagonist inhibited the gastric acid output and plasma beta-EpLI release induced by tetragastrin. These results indicate that beta-EpLI release is stimulated by ingestion of meat soup, duodenal acidification and tetragastrin administration. It is suggested that gastric acid participates, at least in part, in postprandial release of beta-EpLI, probably from the gastrointestinal tract.


Elevated levels of tryptase in bronchoalveolar lavage fluid from patients with sarcoidosis.
Sarcoidosis affecting the lungs may cause obstructive and/or restrictive lung function impairment. The bronchial reactivity is related to the release of histamine from the mast cells. Upon activation mast cells also release tryptase. This enzyme may activate latent collagenase and thus possibly contribute to the fibrosis formation observed in sarcoidosis. We analyzed the bronchoalveolar lavage fluid (BALF) from 13 nonsmoking and untreated patients with sarcoidosis and from 30 healthy volunteers (18 smokers) with regard to the number of mast cells and the tryptase concentration. Concomitantly albumin, fibronectin and hyaluronan were measured as markers of the inflammatory reaction in the alveoli and interstitium. The number of mast cells was higher (p < 0.001) in patients with sarcoidosis than in controls. Also, the concentration of tryptase was significantly higher in patients (225.3 +/- 83.9 [SEM] mU/L) compared to nonsmoking and smoking controls (34.7 +/- 7.8 and 44.7 +/- 13.0 mU/L, respectively; p < 0.01 for both). In addition, the concentrations of albumin, fibronectin and hyaluronan were higher in patients with sarcoidosis compared to the nonsmoking controls (p < 0.001 for all). However, there was no relationship between either the mast cell number or the tryptase concentration and the lung function parameters (VC, TLC, FEV1, FEV%, DLCO). As our patients did not show any functional signs of bronchial obstruction (FEV1 91.7% +/- 13.3 [SD] and FEV% 99.5% +/- 6.4 of predicted) the lack of correlation is not surprising. The high concentrations observed in the BALF of the noncellular components may just reflect an ongoing inflammatory process that may resolve or, if exaggerated, lead to fibrosis.


Hospital days declining for Medicare patients, but up sharply for HMO members.
Data Library: Hospitalization increased among HMO members during 1997 compared with the previous year, and inpatient expenses as a percentage of total medical expenses for HMOs increased slightly for the first time in years. In contrast, more Medicare beneficiaries are staying out of hospitals and seeking care in alternate settings. Review some of the data in two of HICA's most recent reports.


American nurses report safety risk to patients.
American nurses are reporting deteriorating levels of patient care and openly expressing concern about patient safety, the American Nurses' Association has claimed.


Surgical repair of posterior compartment prolapse: preliminary results of a novel transvaginal procedure using a four-armed polypropylene mesh with infracoccygeal and pararectal suspension.
Anatomical defects of the posterior vaginal compartment are a common reason for pelvic floor reconstructive surgery. The implantation of a four-armed monofilamentous polypropylene mesh with infracoccygeal and pararectal suspension is a recently introduced innovative technique, which is believed to reduce the risk of mesh retraction and prolapse recurrences, and additionally, allows a tension-free adjustment of the mesh. In this preliminary case series, we aimed to evaluate feasibility, intraoperative complications and short-term follow-up results of this novel surgical procedure in a multicentre approach. Seventy-three patients undergoing surgery for posterior vaginal compartment prolapse were enrolled. The mean follow-up time was 3.8 months (range: 2-6 months), and follow-up information was available in 60/73 (82.2%) women. Intraoperative complications were observed in 4.2% of cases, 2 patients with blood loss >500 ml, and one bladder injury occurring during concomitant anterior compartment surgery. Importantly, there were no intraoperative complications directly related to the implantation technique (e.g. rectum perforations), and no prolapse recurrences at follow-up examinations 3-6 months postoperatively. Our short-term mesh erosion rate was 3.1%. We conclude that this innovative procedure is a feasible and safe technique for the treatment of posterior vaginal compartment prolapse. Further prospective and multicentre trials are warranted.


Impact of allergic rhinitis on bronchi: an 8-year follow-up study.
Allergic rhinitis is considered a strong risk factor for the onset of asthma. However, few studies addressed this issue from a functional point of view. The aim of this study was to follow up a group of patients with allergic rhinitis to investigate the onset of possible spirometric abnormalities and/or bronchial hyperreactivity (BHR). Eighty-nine patients with moderate-severe persistent allergic rhinitis were prospectively and consecutively evaluated; 940 controls were also included in the study. Clinical examination, skin-prick test, spirometry, and methacholine challenge were performed in all patients every 2 years for 8 years. The number of patients with forced expiratory flow at 25 and 75% of pulmonary volume of <70% of predicted significantly increased during the observation time. At baseline, no subjects had BHR; whereas 34 patients had BHR after 8 years. Sensitization to mites, birch, and Parietaria as well as rhinitis duration are risk factors for these changes. This study highlights the close link between upper and lower airways and suggests that spirometry should be performed in patients with allergic rhinitis.


Operant conditioning of vertical eye movements without visual feedback in the midpontine pretrigeminal cat.
An operant conditioning of vertical eye movements was achieved in the midpontine pretrigeminal cat in total darkness by contingent reinforcement of spontaneous eye movements with lateral hypothalamic (LHT) reward stimulation, when each movement (upward direction was chosen in this experiment) exceeded a preset amplitude. However, the response rates in the dark were lower than those in the light and the time to reach the peak response rate was much longer. Recording of evoked potentials to optic chiasma (OC) stimulation revealed enhancement of late components of the visual cortex (VC) and superior colliculus (SC) responses in relation to eye movements. Sequential records of the averaged evoked responses associated with eye movements indicated that the amplitudes of the late components of the VC and SC waves gradually increased in the course of establishment of the operant conditioning, and decreased gradually during extinction. In a yoked control test, increase in amplitudes of the late components was much less significant during non-contingent reinforcement given independently of the eye movements. These results suggest that 'corollary discharge' may play a critical role as a cue in acquisition of the operant conditioning of vertical eye movements when visual feedback is absent in total darkness.


High glucose-induced barrier impairment of human retinal pigment epithelium is ameliorated by treatment with Goji berry extracts through modulation of cAMP levels.
Human retinal pigment epithelium cells were used to investigate the mechanisms underlying blood-retinal barrier disruption under conditions of chronic hyperglycemia. The treatment with 25 mM glucose caused a rapid drop in the transepithelial electrical resistance (TEER), which was reversed by the addition of either a methanolic extract from Goji (Lycium barbarum L.) berries or its main component, taurine. Intracellular cAMP levels increased concurrently with the high glucose-induced TEER decrease, and were correlated to an increased activity of the cytosolic isoform of the enzyme adenylyl cyclase. The treatment with plant extract or taurine restored control levels. Data are discussed in view of a possible prevention approach for diabetic retinopathy.


Pretreatment with UV light renders the chromatin in human fibroblasts more susceptible to the DNA-damaging agents bleomycin, gamma radiation and 8-methoxypsoralen.
Confluent human fibroblast cultures were pretreated with either 254 nm UV light (UV) or methyl methanesulphonate (MMS), incubated at 37 degrees C and subsequently challenged on ice with bleomycin (BLM), gamma-radiation or 8-methoxypsoralen (MOP). The resulting number of challenge-induced DNA damages (measured as DNA strand breaks or cross-links) were compared with the numbers induced in similarly challenged but non-pretreated control cells. It was found that the timing of the subsequent challenge of cells pretreated with UV did significantly affect the amount of induced DNA damage. When the challenging agents were administered after a 10-20 min incubation period following UV pretreatment, the amount of induced DNA damage was increased 50% over control cells. In contrast, the timing of the subsequent challenge of cells pretreated with MMS had no influence on the level of challenge-induced damage. It is hypothesized that UV-irradiated chromatin undergoes a time-dependent decondensation that renders it more susceptible to the induction of strand breaks and cross-links by BLM, gamma-radiation and MOP. A possible role for chromatin decondensation in UV-induced excision repair is discussed.


Potent and sustained antiviral response of raltegravir-based highly active antiretroviral therapy in HIV type 1-infected children and adolescents.
There are pediatric patients receiving many highly active antiretroviral therapy (HAART) regimens entailing drug resistance mutations that complicate HAART effective therapies. This was a multicenter retrospective study of 19 multidrug-resistant children and adolescents enrolled from July 2007 to October 2009. Patients were nonresponders because no reduction in HIV type 1 (HIV-1) RNA to undetectable levels was observed during their previous antiretroviral treatment history. The long-term effectiveness of raltegravir (RAL)-based salvage therapy was assessed through a longitudinal analysis of immunologic, virologic, and clinical status of the patients. Median age was 16.0 (15.0-18.0) years. At baseline, median HIV-1 RNA was 10,000 (4.0 log10 copies/mL) (interquartile range [IQR]: 4300-83,000), and median CD4T-cell count was 329 (18.2% cells/μL) (IQR: 175-452). The backbone regimen included at least 1 fully active drug in 17/19 (89%) patients. Median follow-up with HAART including RAL was 80.1 weeks (IQR: 49.4-96.4): 16/19 (84%) exposed for >120 weeks and 6/19 (32%) >100 weeks. After RAL-based therapy, 4/19 (21%) patients achieved HIV-1 RNA <400 copies and 13/17 (68%) reached HIV-1 RNA <50 copies: 6 (32%) within the first month and 7 (37%) within the first 4 months. CD4+ T-cell recovery (70% to 90% of the baseline values) was observed in 17/19 (89%) patients. No deaths, AIDS-defining illnesses, or symptoms of severe intolerance were recorded. Only 2 patients experienced mild-moderate short-term skin rash. Two (11%) patients had sustained and optimum adherence to HAART. No patients showed resistance mutations to RAL after follow-up. We observed a sustained antiviral response and improved immunologic indices in multidrug-resistant pediatric patients, most of whom had received RAL as part of salvage regimens with at least 1 fully active drugs.


[Transesophageal echocardiography (Part 3): Clinical application Part 1].
Intraoperative transesophageal echocardiography (TEE) has a wide range of applications including monitoring of left ventricular (LV) function, evaluation of natural and prosthetic valves, detection of intracardiac thrombus, mass and vegetation, assessment of surgical repair of cardiac disease, visualization of intracardiac air, positioning of an intraaortic balloon and a coronary sinus catheter, evaluation of thoracic aortic lesions, and so on. Complications are very rare with TEE, but damage of the esophagus or stomach can occur. Gentle manipulation of the TEE probe is always required. Patients should be carefully examined prior to TEE to exclude potential esophageal or gastric lesions. Monitoring of global and regional LV function is the major application of intraoperative TEE. Fractional shortening, fractional area change, and ejection fraction are widely used estimates of global LV systolic function, but these measurements may not accurately estimate overall ventricular performance when regional wall motion abnormalities (RWMAs) exist. Regional wall motion is highly sensitive to myocardial ischemia, and a decrease or cessation of regional contraction is indicative of impaired myocardial perfusion. Assessment of RWMAs is thus very useful for diagnosis of ischemia. Although RWMAs are not always caused by acute ischemia, a new onset of RWMAs, as seen during surgery, almost certainly indicates myocardial ischemia. TEE also allows evaluation of LV diastolic function by analyzing the transmittal flow velocity.


In vitro transdifferentiation of adult pancreatic acinar cells into insulin-expressing cells.
Despite a recent breakthrough in human islet transplantation for treating diabetes mellitus, the limited availability of insulin-producing tissue is still a major obstacle. Here, we studied whether adult pancreatic acinar cells have the potential to transdifferentiate into islet or beta cells. Pancreatic acini were isolated from 7- to 8-weeks-old male Sprague-Dawley rats and cultured in suspension. Within 1 week, most of the acinar cells lost amylase expression and converted to cells with a duct cell phenotype. Insulin-positive cells were also observed, mainly at the periphery of the acini-derived spheroids. Insulin gene and protein expression was increased. Presence of a few insulin-positive cells coexpressing cytokeratins suggests that a spontaneous acinar to ductal cell transdifferentiation process was further going on towards beta cells. This study provides the first evidence that adult pancreatic acinar cells could be differentiated into insulin-expressing cells in vitro.


High pressure liquid chromatographic determination of rotenone and degradation products in animal chow and tissues.
An analytical procedure is described for determining residues of rotenone, rotenolone, dehydrotenone, and rotenone in admixture in animal chow and tissues. The methanol or ethyl ether extracts from samples of chow and tissues, respectively, are subjected to a liquid-liquid partitioning cleanup with hexane-acetonitrile, further cleanup on a column of silica gel, and subsequent analysis by high pressure liquid chromatography using an ultraviolet absorption detector set at 295 nm. Animal chow, mouse fetuses, and gastrointestinal tracts spiked with 0.5 ppm of each compound in admixture yielded average recoveries of 92, 51, and 79%, respectively; minimum quantities of the 4 compounds detectable in the 3 substrates averaged 0.12, 0.04, ajd 0.14 ppm, respectively. Stability studies indicate that rotenone reacts with animal chow with a half-life of 7--8 days and is photodegraded in incandescent light with a half-life of 0.65 day. No transplacental transfer of rotenone or its products was observed in fetuses from mice receiving 7 consecutive daily doses of rotenone at levels up to 25 mg/kg.


Play-diagnosis and therapy in Sweden: the Erica-method.
The form of play-diagnosis and play-therapy that has been used widely in Sweden during the last 40 years is called the Erica-Method and was developed at the Erica Institute in Stockholm. It has its roots in the World-Technique, developed by the British psychiatrist Dr. Margaret Lowenfeld, and utilizes a standardized material that consists of sandboxes and minature toys. Comprehensive registration and interpretation are provided in the manual, and the method is a very useful tool for better understanding of both developmental, neurological and psychopathological problems of childhood.


Bone Mineral Density in Women Living with Complete Androgen Insensitivity Syndrome and Intact Testes or Removed Gonads.
Complete androgen insensitivity syndrome (CAIS) is due to complete androgen resistance in androgen-dependent tissues. Since androgens are involved in growth, development, and mass maintenance of the skeleton, bone health may be a relevant clinical issue for improving quality of life of women living with CAIS. Bone mineral density (BMD) in women with CAIS and intact gonads has been reported in a normal range, although exceptions are known showing a low BMD mainly at the lumbar level. In women with CAIS and removed gonads, BMD is usually reduced at both the lumbar spine and femoral neck. However, the fracture risk remains largely unknown. In women with CAIS, hormonal replacement therapy may improve BMD, but it does not normalize it. Several factors may be operative (e.g., loss of AR signaling at the bone level, gonadal removal, and age at surgery [before or after attainment of the peak bone mass], inadequate sex steroid replacement therapy, poor compliance with hormonal treatment, high serum FSH levels, lack of testicular protein hormones after gonadal removal), but they are poorly evaluated. In conclusion, the maintenance of testes may represent a strategy to improve bone health in women with CAIS, but a strict follow-up to monitor the cancer risk is mandatory mainly from their 20s onwards. Optimal sex steroid substitutive therapy in adolescence and adulthood is a key factor to improve BMD status in women with CAIS and removed gonads, but conclusive data on optimal management are lacking.


Intrinsic factors for unbound theophylline.
The developmental changes of the ratio of unbound theophylline to total serum concentration have been demonstrated, suggesting clinical usefulness. However, the molecules that can replace the theophylline binding sites of albumin could influence theophylline-binding affinity. We evaluated the intrinsic factors influencing the unbound theophylline ratio. The results suggested that physicians should note that a more intense response might be obtained in children with various intrinsic factors even at the same total theophylline concentration.


Prognostic Significance of Serum CEA for Non-small Cell Lung Cancer Patients Receiving Stereotactic Body Radiotherapy.
To examine the prognostic significance of serum carcinoembryonic antigen (CEA) for stage I non-small cell lung cancer (NSCLC) treated with stereotactic body radiotherapy (SBRT). In total, 129 stage I NSCLC patients were analyzed and divided into two groups: CEA-High (CEA>5 ng/ml) and CEA-Low (CEA≤5 ng/ml). Median follow-up time was 38 months. Overall survival was not significantly different between CEA-High (n=47) and CEA-Low (n=82) patients (57% vs. 63% at 3 years; p=0.39), although progression-free survival (PFS) was significantly worse in CEA-High patients (31% vs. 51% at 3 years; p=0.01). Larger tumor size and high CEA level were independent prognostic factors for worse PFS. Failure pattern analysis showed that regional node or distant recurrence was more common in CEA-High patients (47%) than in CEA-Low patients (29%). Patients with CEA-High stage I NSCLC have a higher risk of regional or systemic relapse and should be followed-up carefully.


[Psychological load factors and control in the work of occupational health nurses].
The purpose of the study was to describe the factors causing psychological loads and control in the work of occupational health nurses. The material was collected using a questionnaire (n = 300). In all, the responses from 195 subjects were available for the present analysis. Cross-tabulation, correlations and percentage distributions were used as the statistical methods. Open-ended questions were qualitatively analyzed using content analysis. Occupational health nurses reported frequent loading due to paper work, the excessive scope of their work and multiple problems with clients. A continuous shortage of time, pressure from unperformed tasks and a lack of opportunities to concentrate on work frequently loaded the subjects. Organization of their work was related to changes in the pace of work. Nurses who estimated their working capacity to be excellent mentioned their professionalism and ability to develop along with the requirements of their work. The findings can be used in planning and developing the work of occupational health nurses and for educational purposes.


[Evaluation and treatment of patients with kidney calculi].
Renal stone disease is a common disorder causing much discomfort and high rates of sick-leave. Surgical treatment has improved dramatically with extracorporeal shock wave lithotripsy, but the recurrence rate is high, and it would be desirable to be able to offer the patients effective steps in prevention of further stone formation. The biochemical abnormalities associated with stone formation are complex and not fully elucidated. It should, however, be possible to reduce the recurrence rate with a relatively simple programme for investigation of the patients. The pathogenesis of renal stones is, therefore, reviewed with reference to a plan for the practical approach to the prevention and management of nephrolithiasis, that has recently been recommended by The National Kidney Foundation, USA.


Management of EGFR Mutation-Positive Non-Small Cell Lung Cancer.
For appropriate treatment selection, the updated NCCN Guidelines for Non-Small Cell Lung Cancer (NSCLC) recommend broad molecular profiling for all patients with nonsquamous disease. Three different tyrosine kinase inhibitors (TKIs) are recommended as first-line treatment of EGFR mutation-positive NSCLC: gefitinib, erlotinib, and afatinib. Most patients whose disease responds will still experience progression, and the type of disease progression drives management. Systemic progression requires switching TKI treatment, whereas patients with oligoprogression and central nervous system progression may have their new lesions treated but continue on their TKI. A new third-generation TKI has been approved and others are currently under development, and new combinations of these drugs with a VEGFR inhibitor offer promise to improve outcomes.


Ozone exposure alters tracheobronchial mucociliary function in humans.
Mucociliary function is a primary defense mechanism of the tracheobronchial airways, and yet the response of this system to an inhalational hazard, such as ozone, is undefined in humans. Utilizing noninvasive techniques to measure deposition and retention of insoluble radiolabeled particles on airway mucous membranes, we studied the effect on mucus transport of 0.2 and 0.4 ppm ozone compared with filtered air (FA) in seven healthy males. During 2-h chamber exposures, subjects alternated between periods of rest and light exercise with hourly spirometric measurement of lung function. Mechanical and mucociliary function responses to ozone by lung airways appeared concentration dependent. Reduction in particle retention was significant (P less than 0.005) (i.e., transport of lung mucus was increased during exposure to 0.4 ppm ozone and was coincident with impaired lung function; e.g., forced vital capacity and midmaximal flow rate fell by 12 and 16%, respectively, and forced expiratory volume at 1 s by 5%, of preexposure values). Regional analysis indicated that mucus flow from distal airways into central bronchi was significantly increased (P less than 0.025) by 0.2 ppm ozone. This peripheral effect, however, was buffered by only a marginal influence of 0.2 ppm ozone on larger bronchi, such that the resultant mucus transport for all airways of the lung in aggregate differed only slightly from FA exposures. These data may reflect differences in regional diffusion of ozone along the respiratory tract, rather than tissue sensitivity. In conclusion, mucociliary function of humans is acutely stimulated by ozone and may result from fluid additions to the mucus layer from mucosal and submucosal secretory cells and/or alteration of epithelial permeability.


Pittsburgh's Freedom House Ambulance Service: The Origins of Emergency Medical Services and the Politics of Race and Health.
This manuscript explores the history of the Freedom House Enterprises Ambulance Service, a social and medical experiment that trained "unemployable" black citizens during the late 1960s and early 1970s to provide then state of the art prehospital care. Through archives, newspapers, personal correspondence, university memoranda, and the medical literature, this paper explores the comparable, yet different roles of the program's two leaders, Drs. Peter Safar and Nancy Caroline. Despite its success in demonstrating national standards for paramedic training and equipment, the program ended abruptly in 1975. And though Pittsburgh's city administration cited economic constraints for its fledgling support of Freedom House, black and majority newspapers and citizens alike understood the city's diminishing support of the program in racial terms. The paper discusses Safar and Caroline's well-intentioned efforts in developing this novel program, while confronting the racial, social, and structural constraints on the program and the limits of racial liberalism.


Significance of incidentally detected subcentimeter enhancing lesions on preoperative breast MRI: role of second-look ultrasound in lesion detection and management.
OBJECTIVE. The purpose of this article is to evaluate the clinical significance of subcentimeter enhancing lesions incidentally detected on preoperative breast MRI in patients with breast cancer and the role of second-look ultrasound in lesion detection and characterization. MATERIALS AND METHODS. From January 2010 through December 2010, 180 lesions measuring less than 10 mm incidentally detected on MRI in 108 women with second-look ultrasound examinations were included (mean patient age, 47.9 years; mean [± SD] lesion size, 5.56 ± 1.64 mm). Seventy-two (40.0%) lesions were smaller than 5 mm, and 108 (60.0%) were 5 mm or larger. Of the 180 lesions, 103 (57.2%) had been biopsied or excised by localization, and 77 (42.8%) with benign ultrasound features had been followed with ultrasound for at least 2 years. Clinical and imaging features were recorded for analysis. RESULTS. Of the 180 enhancing lesions detected on MRI, 14 (7.8%) were malignant and 166 (92.2%) were benign. The malignancy rate of lesions 5 mm or larger was higher than that for lesions smaller than 5 mm (10.2% vs 4.2%), without statistical significance (p = 0.344). The washout enhancement pattern was statistically significantly associated with malignancy (p = 0.032). Although malignant ultrasound features such as nonparallel orientation were more common in malignant lesions, most malignancies had benign features, including oval shape, parallel orientation, and circumscribed margins, with BI-RADS category 4a (n = 12; 85.8%) as the final assessment. CONCLUSION. Second-look ultrasound is a feasible method for evaluating MRI-detected subcentimeter sized lesions in preoperative assessment of patients with breast cancer. A lower threshold should be applied with consideration of MRI features in deciding whether to biopsy or excise these lesions.


Two inhibitors of DNA-synthesis lead to inhibition of cytokine production via a different mechanism.
Methotrexate (MTX) and mycophenolic acid (MPA) are used in the clinic for their immunosuppressive properties. MTX is widely used for the treatment of rheumatoid arthritis (RA). MPA is used to prevent graft rejection and is now experimentally used in systemic lupus erythematosis and RA. It is known that both drugs interfere with DNA synthesis. However, the precise mechanism of action is still debated. We have analysed the effect of the drugs on cytokine production in whole blood during short cultures. The production of T-cell cytokines was inhibited by both drugs. MTX inhibits cytokine production because MTX induces apoptosis in activated T-cells. MPA inhibits cytokine production by preventing T-cells to progress to the S-phase of the cell cycle. Cytokine production by monocytes was slightly decreased by the drugs. The reason for this inhibition is not clear. These results indicate that T-cells are the main target cells of the immunosuppressive drugs MPA and MTX.


Clinical significance of reversed vegetative subtypes of recurrent major depression.
The significance of reversed vegetative forms of atypical depression (AD) was investigated in a sample of 211 outpatients with recurrent major depression. Consistent with several earlier reports, AD patients were younger, had fewer typical symptoms of melancholia, and responded slower to imipramine and psychotherapy treatment given according to protocol. There were few differences between reversed vegetative AD patients with reactive and nonreactive moods; both subforms of AD responded well to monoamine oxidase inhibitor when crossed over after initial protocol treatment failed.


Effects of hippotherapy on people with cerebral palsy from the users' perspective: a qualitative study.
Although there is now some evidence for specific effects of hippotherapy on people with cerebral palsy, these studies fail to provide a comprehensive picture of the effects of hippotherapy. This was the first qualitative study to explore the hippotherapy experience of people with cerebral palsy from a user perspective. The effects of hippotherapy and their context were of particular interest. Seventeen users aged from 4 to 63, with or without their parents, participated in focus groups or individual interviews in six centres in Britain and in Germany. The main effects of hippotherapy, as identified by users and parents, are normalisation of muscle tone, improved trunk control, improved walking ability, carryover effects of hippotherapy to activities of daily living, and increased self-efficacy, confidence, and self-esteem. This study provided unique and new insights into the context in which hippotherapy happens, as well as its effects on impairment, activity, participation, and quality of life in people with cerebral palsy. The study's findings are integrated with the existing literature on motor learning and pedagogy to try to explain the complex effects of hippotherapy as reported by users and parents. A conceptual framework that illustrates these effects and their interactions is introduced.


A Comprehensive Review on Pharmacotherapeutics of Three Phytochemicals, Curcumin, Quercetin, and Allicin, in the Treatment of Gastric Cancer.
Gastric cancer is one of the most common causes of cancer-related death worldwide. Medicinal plants are one of the main sources for discovery of new pharmacological agents especially for treatment of cancers. The aim of the present study is to review pharmacotherapeutic aspects of three mostly studied phytochemicals including curcumin, quercetin, and allicin for management of gastric cancer. Scopus, PubMed, Web of Science, and Google Scholar were searched for the effects of curcumin, quercetin, allicin, and their analogs in gastric cancer. Data were collected up to November 2015. The search terms were "curcumin," "quercetin," "allicin," and "gastric cancer" or "cancer." Curcumin demonstrated anti-angiogenic, anti-proliferative, anti-metastatic, pro-apoptotic, and anti-helicobacter activities. Quercetin inhibited cell growth and induced apoptosis, necrosis, and autophagy as well as anti-Helicobacter activity. Allicin showed apoptotic and anti-Helicobacter properties. All three natural compounds had low bioavailability. Although preclinical studies demonstrated the activity of curcumin, quercetin, and allicin in gastric cancer, clinical trials are needed to confirm their effectiveness. Applying their possible synergistic action and suitable drug delivery system in clinical studies can be also an attractive approach with the purpose of finding new extremely efficient anti-gastric cancer agents. Curcumin, quercetin, and allicin seem to be good candidates for management of gastric cancer through their pro-apoptotic, anti-proliferative, and anti-helicobacter activities.


Multivesicular liposomes for sustained release of naltrexone hydrochloride: design, characterization and in vitro/in vivo evaluation.
Multivesicular liposomes containing naltrexone hydrochloride (DepoNTX) was prepared by using the traditional DepoFoam technology and the key formulation factors on encapsulation efficiency and particle size were investigated. A morphological characterization and in vitro/in vivo release assay was also carried out. NTX was successfully encapsulated in DepoNTX with good yield and showing the spherical, smooth and multivesicular characteristics of particle by a light microscope. The in vitro studies in human plasma and sodium chloride showed that 80-85% of NTX encapsulated in MVLs released slowly from particles over 5 days. In vivo study, after a single dose of 2.0 mg/kg of DepoNTX formulation administered subcutaneously in rats, plasma NTX levels were maintained at a relatively constant level above 10 ng/mL for approximately 120 h, while after administered NTX solution, NTX level was quickly decreased below 10 ng/mL within 20 h. The results of the study demonstrated that DepoNTX was very promising candidate for sustained release delivery of naltrexone hydrochloride.


Sequestrated meningocele of the scalp: diagnostic value of hair anomalies.
Clinical aspects of sequestrated meningocele can be varied, causing difficulties in histopathological diagnosis. The meningeal tissue is scanty and appears as nonspecific connective tissue, therefore it may be overlooked. One classical and two unusual clinical presentations of sequestrated meningocele are described: one of the latter presenting as two atrophic midline bald patches, and the other as a tiny occipital midline hair tuft. In the unusual cases, the pathologic diagnosis was made possible only with the combination of clinical, histologic, and immunohistochemical studies. Sequestrated meningocele should be included in the differential diagnosis whenever hair abnormalities are observed in neonates and young children. We believe that there is a causal relationship between anomalies of the central nervous system and the cutaneous adnexal malformations.


Laparoscopic treatment of an interstitial pregnancy.
Interstitial (cornual) pregnancies occur rarely, estimated at 1 for every 2500 to 5000 live births. Since the morbidity and mortality are high, the correct diagnosis must be made and treatment begun promptly. A number of management options have been described, including conservative treatments such as expectant management, methotrexate injections (local or systemic), potassium chloride injections (local), and prostaglandin administration. Among conservative surgical treatments, hysteroscopy has been performed successfully to diagnose and treat the condition. To my knowledge, this is the first report of laparoscopic treatment of interstitial pregnancy.


Influence of infant diets on the ecology of the intestinal tract of human flora-associated mice.
The effect of diet on intestinal ecology was studied in germ-free mice that were inoculated orogastrically with predominant intestinal flora components isolated from the feces of breast-fed human infants. The flora components colonized the intestines of mice and persisted at fixed population levels. Groups of flora- associated mice were fed either human milk, bovine milk, whey-dominant formula, or formula modifications exclusively for 2 weeks, and then examined for changes in small intestinal and cecal flora composition, cecal pH, and resistance to intestinal colonization with Salmonella typhimurium. Dietary variations influenced the composition of the flora to a moderate degree but the differences were generally not statistically significant. However, the addition of bovine lactoferrin to the whey-dominant formula resulted in significantly greater counts of Bifidobacterium, Bacteroides, Enterococcus and total aerobes in the small intestine when compared with mice fed unsupplemented formula. Bifidobacterium was present in large numbers in both the ceca and small intestines of mice fed the lactoferrin-supplemented formula. Despite similarities in intestinal flora patterns among mice fed the various diets, human milk consumption resulted in a lower pH of cecal contents and a greater resistance to colonization by Salmonella typhimurium after orogastric challenge than the consumption of the other diets.


Involvement of ATP-sensitive K(+) channels in the peripheral antinociceptive effect induced by the alpha(2)-adrenoceptor agonist xylazine.
Xylazine is an alpha(2)-adrenergic agonist extensively used in veterinary medicine and animal experimentation for producing antinociception, sedation, and muscle relaxation. The nitric oxide (NO) / cGMP / ATP-sensitive K(+) (K(ATP)) channel pathway has been proposed as the action mechanism of peripheral antinociception of several groups of drugs, including opioids and nonsteroidal analgesics. Considering the lack of knowledge regarding the mechanisms involved in xylazine effects, the present study investigated the contribution of K(+) channels on peripheral antinociception induced by xylazine using the rat paw pressure test, in which hyperalgesia was induced by intraplantar injection of prostaglandin E(2). Xylazine administered into the right hind paw elicited a local antinociceptive effect, since only much higher doses produced a systemic effect in the contralateral paw. The peripheral antinociceptive effect induced by xylazine was antagonized by glibenclamide, a specific blocker of K(ATP) channels. In another experiment, tetraethylammonium, a voltage-dependent K(+)-channel blocker, and paxilline and dequalinium, which are selective blockers for the large- and small-conductance Ca(2+)-activated K(+) channels, respectively, were ineffective at blocking xylazine antinociception. These results provide evidence that the peripheral antinociceptive effect of xylazine probably results from K(ATP)-channel activation, while the voltage-dependent K(+) channels, small- and large-conductance Ca(2+)-activated K(+) channels, appear not to be involved in this mechanism.


Tetracycline release from tripolyphosphate-chitosan cross-linked sponge: a preliminary in vitro study.
The aim of this study was to design a tripolyphosphate-chitosan cross-linked tetracycline-containing (TPP-TC) sponge that slowly releases tetracycline, for future periodontal applications. Chitosan sponge was made by freezing and drying 2.5% chitosan solution. Tripolyphosphate-chitosan cross-linked (TPP) sponge was made by immersing the chitosan sponge in tripolyphosphate solution and air drying it. Tetracycline-containing chitosan (TC) sponge was prepared by freezing and drying a mixture of chitosan and tetracycline. TPP-TC sponge was made by immersing the TC sponge in tripolyphosphate solution. The weight, thickness and diameter of the four chitosan sponges were recorded. Their surface microstructures were inspected using scanning electron microscopy. The amount of tetracycline released from the sponges was analyzed by spectrophotometry. Antimicrobial activities of the residual sponges were tested against Staphylococcus aureus and Escherichia coli. The topography of the scaffolds was intact after the addition of tetracycline. However, increased surface irregularities were noted. In sponges with tripolyphosphate, intensified surface folding was observed. The weight of the sponges increased after tripolyphosphate and tetracycline were added, but their thicknesses and diameters decreased after cross-linking. Tetracycline was detected in the solution containing TPP-TC sponges until day 11. On day 7, the tetracycline released from TC sponges was less than that released from TPP-TC sponges. Bacterial growth was inhibited by sponges containing tetracycline. The inhibitory effect of the TPP-TC sponges was detectable until day 11. Our data showed that TPP-TC sponge was suitable as a slow-release device for tetracycline and that it maintained antimicrobial effects against the bacteria tested for up to 11 d.


Photonic crystal fibers confining light by both index-guiding and bandgap-guiding: hybrid PCFs.
We propose two kinds of hybrid photonic crystal fiber (PCF) structures and investigate the properties of such PCFs in detail. The modal effective index, mode field area, confinement loss, group velocity dispersion, and birefringence are numerically simulated and compared with those of the corresponding index-guiding and bandgap PCFs, which allows for a deeper understanding of the guiding mechanism of the hybrid PCFs. The advantages of hybrid PCFs and potential applications are also discussed.


Effect of vitamin C deficiency and excess on the liver: a histopathological and biochemical study in guinea pigs fed normal or high cholesterol diet.
When guinea pigs were kept on a restricted vitamin C intake of only 0.5 mg daily, their serum ascorbic acid fell to 0.16 +/- 0.06 mg/d1 in 16 weeks as compared to 0.73 +/- 0.11 in control. This was associated with significant increase in liver cholesterol and triglycerides. When they were simultaneously challenged with a high cholesterol load, this fat accumulation was markedly exaggerated. The weight of the liver now increased by almost two-and-half times. Liver cholesterol rose to 12.90 +/- 2.63 mg/gm as compared to 3.23 +/- 0.56 mg/gm with low vitamin C alone. Histopathology showed marked distension and vacuolation of hepatocytes, focal necrosis and fibroplasia. Administration of excess vitamin C (100 mg daily) significantly countered these changes. The vitamin C-lipid relationship has important clinical bearings and liver could be an important site of vitamin C action.


Correlation of a disease scoring system with arterial PO2 values in respiratory syncytial virus infection in calves.
The mean arterial PO2 value measured in blood obtained by puncture of the brachial artery of 20 calves with acute clinical signs of a bovine respiratory syncytial virus (BRSV) infection was 8.4 +/- 1.9 kPa. The values differed significantly from arterial PO2 values of eleven healthy calves (mean 14.2 +/- 1.5 kPa). A disease scoring system is presented based on the type of respiration and the findings on auscultation. A high correlation (r = -0.87) was found between disease scores and arterial PO2 values. This indicates that the described disease scoring system can be a useful tool in the evaluation of the severity and course of BRSV infections in calves, and could be used for evaluating the efficacy of BRSV vaccines in the field. The course of disease was studied in 127 calves with clinical signs of serologically proven BRSV infection. Animals with mild respiratory signs during the acute phase of disease remained free of severe respiratory problems until the end of a 35-day examination period. Mean disease scores indicated that animals with severe signs in the acute phase often developed persistent respiratory problems.


[Features of the extracellular matrix of fibroadenomas and leaf-shaped tumors of the human breast (immunomorphologic study)].
Fibronectin and collagen I, III, IV, V distribution in preexisting and newly formed connective tissue of fibroadenomas and leaf-like human breast tumour was studied by the immunofluorescent method. Extracellular matrix of a newly formed connective tissue was characterized by the predominance of collagen type III, the presence of collagen type IV, a high content of fibronectin in a leaf-like tumour. Such characteristics of the extracellular matrix structure in benign tumours are interpreted as a manifestation of desmoplasia.


Hearing loss and cochlear pathology in monkeys after noise exposure.
Old World monkeys were exposed to octaveband noise from 0.5 to 8 kHz at 120 dB SPL, 8 hours daily for 20 days. Restricted permanent threshold shifts and localized loss of outer hair cells were produced, which were reasonably well correlated with the exposure frequencies. There was also a loss of both inner and outer hair cells at the extreme basal end of Corti's organ, regardless of the exposure frequency. Implications for human inner ear pathology are discussed.


The reovirus sigma1 aspartic acid sandwich: a trimerization motif poised for conformational change.
Reovirus attachment protein sigma1 mediates engagement of receptors on the surface of target cells and undergoes dramatic conformational rearrangements during viral disassembly in the endocytic pathway. The sigma1 protein is a filamentous, trimeric molecule with a globular beta-barrel head domain. An unusual cluster of aspartic acid residues sandwiched between hydrophobic tyrosines is located at the sigma1 subunit interface. A 1.75-A structure of the sigma1 head domain now reveals two water molecules at the subunit interface that are held strictly in position and interact with neighboring residues. Structural and biochemical analyses of mutants affecting the aspartic acid sandwich indicate that these residues and the corresponding chelated water molecules act as a plug to block the free flow of solvent and stabilize the trimer. This arrangement of residues at the sigma1 head trimer interface illustrates a new protein design motif that may confer conformational mobility during cell entry.


Neuroprotection in cerebral ischaemia: facts and fancies--the need for new approaches.
'Neuroprotection' is a term used to describe the putative effect of interventions protecting the brain from pathological damage. In occlusive stroke, the concept of neuroprotection involves inhibition of a cascade of pathological molecular events occurring under ischaemia and leading to calcium influx, activation of free radical reactions and cell death. This article will summarize neuroprotection trials to date, some facts and fancies about neuroprotection, ischaemic pathophysiology and possible reasons for the apparent failure of human neuroprotective stroke trials. In the acute stage of occlusive stroke, moderate reduction of blood flow results in a 'penumbra' of brain cells, often surrounding a core infarct, in which brain cells survive for a few hours but gradually die if reperfusion is not established. Increased knowledge of the complex pathophysiology in acute ischaemic stroke has led to the development of a great number of candidates for neuroprotective interventions. Many neuroprotective agents have proven efficacious in animal models, but so far no human study has shown a statistically significant benefit in patients with acute ischaemic stroke on primary endpoint measures. Some neuroprotective agents show beneficial effects on post hoc analyses, and some studies are still ongoing. FANCIES: In the early years of neuroprotective studies in stroke, it was thought that a drug with almost no adverse effects could be given by ambulance staff on the way to hospital and induce a clinically significant effect on outcome. Since there were only benefits and no risks, diagnostic skills by neurologists and neuroradiological evaluations would no longer be required. WHY HAVE NEUROPROTECTIVE AGENTS FAILED IN HUMAN STROKE TRIALS? There are several possible explanations why neuroprotective trials have been unable to prove an effect in addition to the eventuality that the basic concept is wrong. The effects of neuroprotective agents on infarct size are time dependent, and treatment has often been initiated much later than in successful experimental stroke models. Insufficient doses of the drugs and slow availability of the drug at the target area may be other explanations. Too small sample sizes in trials and imbalance of prognostically important baseline variables are examples of shortcomings in trial methodology. WHAT CAN BE DONE? FUTURE NEW APPROACHES: IN ANIMAL MODELS, preclinical testing of neuroprotective candidates should be standardized. Conventional stroke models with young and healthy animals may be replaced by older animals with common co-morbidity such as atherosclerosis. Highly effective new neuroprotective agents need to be discovered, and combination therapies should be tried. IN CLINICAL TRIALS, the greatest chances of success may be with neuroprotective concepts involving mechanisms in both ischaemic and reperfusion pathophysiology, in combination with a thrombolytic therapy protocol. Neuroprotective agents, possibly combinations of agents, should preferably approach several of these mechanisms. Treatments should be initiated early, at least within 3 h after stroke onset, by an intravenous route. The selected compound(s) should easily pass the blood-brain barrier. Neuroprotective agents shown to be highly effective in stroke models should be preferred, and doses used experimentally should be used also in the clinical setting. Trials should use randomization techniques, which reduce imbalances of prognostically important baseline variables, and the estimated sample size of a trial should be based on expectations of a modest clinical effect.


Overview of supportive care in patients receiving chemotherapy: antiemetics, pain management, anemia, and neutropenia.
With advancements in the field of oncology, more and more people are living with cancer. The prevalence of invasive cancer in the United States is estimated to be almost 12 million. The treatment of cancer as well as the malignancy itself can cause an immense number of side effects and other complications. This article explores the fundamentals of supportive care in patients receiving chemotherapy and radiation treatment including prevention of nausea and vomiting, pain management, treatment of anemia and neutropenia. Proper supportive care can help improve clinical outcomes, reduce medical costs, and help patients with cancer live longer, happier, and healthier lives. For these reasons, it is important for pharmacists to possess a solid understanding of how to prevent and treat the adverse effects of chemotherapy and radiation treatment.


An investigation of the action of porcine pancreatic alpha-amylase on native and gelatinised starches.
The action of pancreatic alpha-amylase (EC 3.2.1.1) on various starches has been studied in order to achieve better understanding of how starch structural properties influence enzyme kinetic parameters. Such studies are important in seeking explanations for the wide differences reported in postprandial glycaemic and insulinaemic indices associated with different starchy foodstuffs. Using starches from a number of different sources, in both native and gelatinised forms, as substrates for porcine alpha-amylase, we showed by enzyme kinetic studies that adsorption of amylase to starch is of kinetic importance in the reaction mechanism, so that the relationship between reaction velocity and enzyme concentration [E0] is logarithmic and described by the Freundlich equation. Estimations of catalytic efficiencies were derived from measurements of kcat/Km performed with constant enzyme concentration so that comparisons between different starches were not complicated by the logarithmic relationship between E0 and reaction velocity. Such studies reveal that native starches from normal and waxy rice are slightly better substrates than those from wheat and potato. After gelatinisation at 100 degrees C, kcat/Km values increased by 13-fold (waxy rice) to 239-fold (potato). Phosphate present in potato starch may aid the swelling process during heating of suspensions; this seems to produce a very favourable substrate for the enzyme. Investigation of pre-heat treatment effects on wheat starch shows that the relationship between treatment and kcat/Km is not a simple one. The value of kcat/Km rises to reach a maximum at a pre-treatment temperature of 75 degrees C and then falls sharply if the treatment is conducted at higher temperatures. It is known that amylose is leached from starch granules during heating and dissolves. On cooling, the dissolved starch is likely to retrograde and become resistant to amylolysis. Thus the catalytic efficiency tends to fall. In addition, we find that the catalytic efficiency on the different starches varies inversely with their solubility and we interpret this finding on the assumption that the greater the solubility, the greater is the likelihood of retrogradation. We conclude that although alpha-amylase is present in high activity in digestive fluid, the enzymic hydrolysis of starch may be a limiting factor in carbohydrate digestion because of factors related to the physico-chemical properties of starchy foods.


[Syndrome of lower limb volume enlargement in varicosity: causes and medical approaches].
This paper provides the results of examination of 413 patients aged 15 to 79 years (mean age 43.2 years) with different stages of CVI seen from 1995 to 2005. A complex of methods was employed: the clinical nmltimodality examination, multilevel volumetric monitoring before and after daily orthostatic loading, occlusion plethysmography, multilevel ultrasound duplex scanning of the venous system arid subcutis as well as radiography. Only in the third of cases (n=149, 36.0%) was primarily of distal character attended by lesion of the foot and leg, with clear daily dynamics and dependence on the daily orthostatic loading-eaema proper. Two types of edema were distinguished: 1)with pronounced daily dynamics and return to the initial parameters in the morning hours (131 patients) and 2) with moderate daily dynamics of edema and the lack of return to the initial parameters in the morning hours (18 patients). Such difference stems from the type of coexistent lymphatic insufficiency (with a high and low drop). However, only the first type is initially determined by venous insufficiency. The majorityof this group patients were found to suffer thrombosis of the ti-bial veins in the presence of varicosity running a prolonged course. Hinetyone patients (22.0%) had a proximally oriented enlargement, with pronounced orthostasodependerice, of the muscle segments of the limb because of orthostasodependent phlebopaxhy. In the remaining 173 (41.9%) patients examined, vascular eaema was coupled with non-vascular causes of limb size enlargement (arthrosis of leg joints, lipoedema) or the latter ones were isblated. The aim of the present study was to analyze the causes of the syndrome of limb size enlargement in varicosity with the purpose of upgrading the efficacy and trend of the treatment.


Supporting the adolescent mother-infant relationship: preliminary trial of a brief perinatal attachment intervention.
The purpose of this study is to test a brief, attachment intervention added to routine maternity care that aims to improve the adolescent mother-infant relationship during transition to motherhood. A pre-test, post-test, peer-control-group trial was set in a large tertiary maternity hospital in Melbourne, Australia. Participants were multi-cultural, pregnant adolescents (n = 97). The two-session 'AMPLE' intervention was provided in late pregnancy and neonatally. The main outcome measure was mother-infant interaction quality at age 4 months, blind-coded using the Emotional Availability Scales (EAS) (fourth edition). Study acceptability was high: participation rate 82.9 % and completion rate 75.3 %. Thirty-five participants received the intervention plus usual care (intervention group) and 38 received usual care (control group). There were no pre-test between-group differences across demographic, psychosocial or obstetric domains. At post-test, mother-infant interaction was significantly better in the intervention group. MANOVA analyses showed an overall intervention effect on emotional availability in 20 min of free play (n = 73), F (6,65) = 5.05, p < .01, partial η (2) = .32, and in 25 min of play plus brief separation-reunion (n = 55), F (6,48) = 2.72, p = .02, partial η (2) = .25. T tests showed significant between-group differences in specific EAS subscales. All effect sizes were medium-large. This promising intervention appears to exert a clinically meaningful effect on the adolescent mother-infant relationship. Further research is warranted to replicate the findings and confirm causality. The study suggests a brief attachment focus, incorporated into routine maternity care, could influence the developmental trajectory of infants of young mothers from birth.


Methotrexate: new mechanisms and old toxicities.
Over the last several years, information on methotrexate's mechanism(s) of action (which affects its efficacy) and toxicities continue to evolve. This popular second line agent (DMARD) is a potent anti-inflammatory drug, with effects on LTB4 and adenosine release (EC-50: 1-13 nM). As such, it may be a sufficiently potent anti-inflammatory drug to affect rheumatoid arthritis's basic course, as shown by a recent meta-analysis where methotrexate equalled gold and was better than azathioprine, when examining radiographic erosions. Its toxicities continue to be documented, with cirrhosis occurring between 2:100 and 1:1000 cases. Pneumonitis continues to be found. NSAID-MTX interactions, too, have been documented, although their kinetic mechanisms remain controversial.


Molecular manipulation of neural precursors in situ: induction of adult cortical neurogenesis.
Over the past three decades, research exploring potential neuronal replacement therapies have focused on replacing lost neurons by transplanting cells or grafting tissue into diseased regions of the brain. Over most of the past century of modern neuroscience, it was thought that the adult brain was completely incapable of generating new neurons. However, in the last decade, the development of new techniques has resulted in an explosion of new research showing that neurogenesis, the birth of new neurons, normally occurs in two limited and specific regions of the adult mammalian brain, and that there are significant numbers of multipotent neural precursors in many parts of the adult mammalian brain. Recent findings from our lab demonstrate that it is possible to induce neurogenesis de novo in the adult mammalian brain, particularly in the neocortex where it does not normally occur, and that it may become possible to manipulate endogenous multipotent precursors in situ to replace lost or damaged neurons. Recruitment of new neurons can be induced in a region-specific, layer-specific, and neuronal type-specific manner, and newly recruited neurons can form long-distance connections to appropriate targets. Elucidation of the relevant molecular controls may both allow control over transplanted precursor cells and potentially allow the development of neuronal replacement therapies for neurodegenerative disease and other CNS injuries that do not require transplantation of exogenous cells.


Surfactant induced glistenings: surface active ingredients in ophthalmic solutions may enhance water entry into the voids of implanted acrylic intraocular lenses.
To investigate the light scattering properties of acrylic intraocular lenses (IOLs) placed in eyes treated with diclofenac sodium (Diclod, Wakamoto, Japan) and betamethasone phosphate (Rinderon, Shionogi, Japan) ophthalmic solutions. The light scattering properties of IOLs (MA30BA, Alcon laboratories) placed in 32 eyes treated with Diclod and 31 treated with Rinderon were evaluated 3 years after implantation using Scheimpflug photography. The averaged intensity of glistenings was 9.0 CCT (computer compatible tapes) in the Diclod test group and 4.2 CCT in the Rinderon test group (p = 0.002). The intensity of surface light scattering for the Diclod and Rinderon test groups was 24.0 CCT and 26.9 CCT, respectively (p = 0.081). The Diclod test group had a greater number of glistenings than the Rinderon test group. Both drugs have similar anti-inflammatory properties and Diclod, unlike Rinderon, also contains the surfactant polysorbate. We proposed that the presence of surfactant, or other ingredient, in commercially available eyedrops may enhance the development of glistenings.


Elevated levels of amniotic fluid alpha-fetoprotein: sonographic evaluation.
From 1978 to 1990, 263 fetuses with an elevated level of amniotic fluid alpha-fetoprotein (AF-AFP) (> 2.0 multiples of the median) were examined with targeted fetal sonography. All cases of AF-AFP elevation among 22,355 genetic amniocenteses were represented. Sonography correctly showed 32 open neural-tube defects, including 20 myelomeningoceles, and depicted 94% (63 of 67) of the anomalous fetuses. Two of five anomalous fetuses with normal sonograms, however, had extremely high AF-AFP levels leading to prospectively correct diagnoses of congenital nephrosis. Therefore, programmatically, 97% (65 of 67) of the anomalous fetuses were recognized. The three programmatic misdiagnoses were all detected in the neonatal period and surgically corrected; subsequent development was normal. The combination of an elevated AF-AFP level and a detailed sonogram allowed distinction between a normal and an anomalous fetus in 99% of cases. When elevated levels are noted, AF-AFP analysis followed by detailed sonography is highly successful for the detection and characterization of anomalous fetuses and the recognition of normal fetuses with physiologic increases of this protein in the amniotic fluid.


Shock-induced dispersion of ventricular repolarization: implications for the induction of ventricular fibrillation and the upper limit of vulnerability.
Shock-induced dispersion of ventricular repolarization (SIDR) caused by an electrical field stimulus has been suggested as a mechanism of ventricular fibrillation (VF) induction; however, this hypothesis has not been studied systematically in the intact heart. Likewise, the mechanism underlying the upper (ULV) and lower (LLV) limit of vulnerability remains unclear. In eight Langendorff-perfused rabbit hearts, monophasic action potentials were recorded simultaneously from ten different sites of both ventricles. Truncated biphasic T wave shocks were randomly delivered at various coupling intervals and strengths, exceeding the vulnerable window, ULV, and LLV, SIDR, defined as the difference between the longest and shortest postshock repolarization times, was 64 +/- 15 msec for shocks inducing VF. SIDR was 41 +/- 17 msec for shocks delivered above the ULV, and 33 +/- 14 and 27 +/- 8 msec for shocks delivered 10 msec before and after the vulnerable window, respectively (all P < 0.01 vs VF-inducing shocks). Although SIDR was larger for shocks delivered below the LLV (93 +/- 24 msec, P < 0.01 vs VF-inducing shocks), the repolarization extension was significantly smaller for shocks below the LLV (10.3% +/- 3.9% vs 16.3% +/- 4.9%, P < 0.01). SIDR is influenced by the shock timing and intensity. Large SIDR within the vulnerable window and an SIDR decrease toward its borders suggest that SIDR is essential for VF induction. The decrease in SIDR toward greater shock strengths may explain the ULV. Small repolarization extension for shocks below the LLV may explain why these shocks, despite producing large SIDR, fail to induce VF.


Impact of an early physiotherapy program after kidney transplant during hospital stay: a randomized controlled trial.
Cardiorespiratory and musculoskeletal dysfunctions are common in the postoperative period of kidney transplant patients and are often accompanied by low exercise tolerance. The purpose of this study was to evaluate the impact of an early physiotherapy program during hospital stay on functional capacity and peripheral and respiratory muscle strength after kidney transplant. An open, randomized clinical trial was conducted in patients undergoing living donor kidney transplant. Sixty-three patients were included (intervention group-IG: n = 30; control group-CG: n = 33). IG received an early physiotherapy program from first postoperative day until hospital discharge and CG received standard care. The variables of interest were measured preoperatively and at discharge except for respiratory muscle strength and vital capacity (VC), which were also measured on the first postoperative day. Functional capacity was evaluated through six-minute walk test (6MWT); peripheral and respiratory muscle strength using a dynamometer and manovacuometer, respectively; and VC through spirometer. After surgery, there was a reduction in functional walking capacity and peripheral muscle strength without different between groups (p > 0.05); however, respiratory muscle strength was significantly higher in IG (p < 0.001) at hospital discharge, when comparing with CG. An early physiotherapy program during hospitalization for patients undergoing living donor kidney transplant caused a lower reduction in respiratory muscle strength and without additional benefits in the functional capacity, when compared to a control group, although the clinical relevance of this finding is uncertain.


Variability of mitotic activity in chicken embryo tissues.
On testing antimitotic substances in chicken embryos the authors encountered considerable changes in the mitotic activity which were difficult to explain. Mitotic indexes (MI) of several tissues sampled during a 24 hour period were measured and compared. The statistical significance of the results was verified by the U- and t-tests. Marked changes in mitotic activity dependent on daytime were found in all cases. Maximum MI values were measured around the 12th, minimum between the 2nd and 6th hours. These variations cannot be explained by the facts known so far. The question arises whether this time regulation of mitotic activity is typical only for embryonic or bird tissues, or whether it may be a general biological phenomenon.


Insufficient evidence of effect of periodontal treatment on prevention or management of cardiovascular disease.
The Cochrane Oral Health Group's Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), Medline, Embase, CINAHL, OpenGrey, the Chinese BioMedical Literature Database, the China National Knowledge Infrastructure and the VIP database, the US National Institutes of Health Trials Register, the World Health Organisation (WHO) Clinical Trials Registry Platform and Sciencepaper Online databases were searched with no restrictions on language or date. Two reviewers independently selected studies and only randomised controlled trials (RCTs) and quasi-RCTs with follow-up times ≥ one year were considered. Data extraction and risk of bias assessment were carried out independently and in duplicate. Standard Cochrane methodological approaches were used. Only one trial involving 303 patients that compared scaling and root andomiz (SRP) with community care was included. It was considered to be at high risk of bias. No data on deaths (all-cause or CVD-related) were reported. There was insufficient evidence to determine the effect of SRP and community care in reducing the risk of CVD recurrence in patients with chronic periodontitis (risk ratio (RR) 0.72; 95% confidence interval (CI) 0.23 to 2.22; very low quality evidence). The effects of SRP compared with community care on high-sensitivity C-reactive protein (hs-CRP) (mean difference (MD) 0.62; -1.45 to 2.69), the number of patients with high hs-CRP (RR 0.77; 95% CI 0.32 to 1.85) and adverse events (RR 9.06; 95% CI 0.49 to 166.82) were also not statistically significant. The study did not assess modifiable cardiovascular risk factors, other blood test results, heart function parameters or revascularisation procedures. We found very low quality evidence that was insufficient to support or refute whether periodontal therapy can prevent the recurrence of CVD in the long term in patients with chronic periodontitis. No evidence on primary prevention was found.


[A retrospective cohort study on the survival of blood-borne human immunodeficiency virus cases in a county, China].
To understand the survival rate of adult blood-borne human immunodeficiency virus (HIV) cases in a county. A retrospective cohort study was carried out to determine the survival from HIV infection and related factors among 78 adult HIV cases infected by blood and confirmed by the end of 2002. Kaplan-meier method was used to describe the survival distribution and Cox proportional hazard model was used to determine the factors associated with the survival time. The total mortality after infection was 78.57/1000 p-y and AIDS related mortality was 72.95/1000 p-y. The median survival time was 7.40 years (95% Confidence Interval: 6.79 - 8.02). After adjustment for the clinical stage at presentation (HIV or AIDS), people who got infected at the age of 30 - 40 years or infected by the end of 1995 would proceed to death slower than the other groups. The survival of HIV cases infected by blood at the county level might have been underestimated and should be adjusted when HIV/AIDS was estimated and projected. Survival was associated with age when infection started so different survival functions should be used on different age groups that infection started.


Nutritional practices of male cyclists before and during an ultraendurance event.
The aim of the study was to investigate the pre- and during-race nutritional intake of cyclists competing in a 210-km 1-day ultraendurance cycle race. Forty-five endurance-trained male cyclists participated in this dietary survey and completed a 3-day dietary record. Mean reported carbohydrate (CHO) intake over the 3 days before the race (5.6 +/- 1.7 g/kg) was below the recommended guidelines of 7-10 g/kg. Although 57% of participants indicated that they CHO loaded 1-3 days before the race, only 23% of these participants achieved CHO intakes of > or =7 g/kg over the 3-day period before the race, demonstrating a discrepancy between perceived and actual intakes of CHO. Most participants indicated the use of CHO supplements before (84%) and during (98%) the race and achieved a CHO intake of 63 +/- 23 g/hr during the race. Although most cyclists failed to meet recommended prerace CHO intakes, most achieved the recommended CHO intakes during the race.


Shoulder load during synchronous handcycling and handrim wheelchair propulsion in persons with paraplegia.
To compare the shoulder load during handcycling and wheelchair propulsion under similar conditions of external power in persons with spinal cord injury. Cross-sectional. Eight men with spinal cord injury. Kinetics and kinematics were measured during handbike and wheelchair propulsion at 25, 35, 45 and 55 W on a treadmill. Shoulder load (glenohumeral contact forces, relative muscle forces) was calculated with the Delft Shoulder and Elbow Model. At all power output levels, glenohumeral contact forces were significantly lower during handcycling compared with wheelchair propulsion (p < 0.001). At 55 W, the mean glenohumeral contact force was 345 N for hand-cycling, whereas it was 585 N for wheelchair propulsion. Also, relative muscle forces were lower during handcycling. The largest differences between handbike and wheelchair propulsion were found in the supraspinatus (4.5% vs. 20.7%), infraspinatus (3.7% vs. 16.5%) and biceps (5.0% vs. 17.7%). Due to continuous force application in hand-cycling, shoulder load was lower compared with wheelchair propulsion. Furthermore, muscles that are prone to overuse injuries were less stressed during handcycling. Therefore, handcycling may be a good alternative for outdoor mobility and may help prevent overuse injuries of the shoulder complex.


Influence of pre-, intra- and post-operative parameters of donor liver on the outcome of isolated human hepatocytes.
The aim of the present study was to analyse, retrospectively on a large panel of patients (149), the influence of the donor liver characteristics on the outcome of human hepatocyte isolation obtained from resected liver biopsies from surgical waste after hepatectomy. Among the pre-operative parameters, the type of disease, age and sex of the patient, previous chemotherapy, alcohol or tobacco consumption did not affect the yield, viability, attachment rate and function of the isolated human hepatocytes. Pre-operative biological and anatomopathological data indicated that, while mild steatosis (</=10% steatotic hepatocytes) did also not affect the outcome of hepatocyte isolation, stronger steatosis (>10% steatotic hepatocytes) tended to decrease hepatocyte yield. Cholestasis, as assessed by gamma-glutamyl transferase serum values, significantly negatively correlated with the percentage of digested liver and the yield of viable cells. Intra-operative clamping time, that is, warm ischaemia, longer than 30 min was found to decrease both the percentage of digested liver and cell yield. Among the post-operative parameters, the percentage of digested liver decreased when biopsy weights were higher than 100 g, the use of glue tended to increase both the percentage of digested tissue and the yield of viable cells.In conclusion, human diseased livers appear to be a valuable source of isolated functional human hepatocytes. We recommend, for an optimal isolation, to use liver biopsies weighing less than 100 g, to glue the section surfaces of the biopsies and to avoid the use of moderate steatotic livers (>10% steatotic hepatocytes) and cholestatic livers, as well as livers undergoing warm ischaemia or clamping during resection due to the decrease in cell yield.


Prevalence of Semicircular Canal Hypoplasia in Patients With CHARGE Syndrome: 3C Syndrome.
CHARGE syndrome refers to a syndrome involving coloboma, heart defects, atresia choanae, retardation of growth and development, genitourinary disorders, and ear anomalies. However, Verloes revised the characteristics of CHARGE syndrome in 2005 to define this syndrome more broadly. Deficiency of the semicircular canals is now a major criterion for CHARGE syndrome. To characterize patients with CHARGE syndrome at our center using Verloes' criteria and to reevaluate the nomenclature for this condition. We performed a medical chart review of patients with CHARGE syndrome and reviewed their temporal bone imaging studies at a tertiary care children's hospital affiliated with Washington University in St Louis. Two authors independently reviewed each imaging study (A.W. and K.H.). Radiologic studies, physical findings, genetic tests, and other diagnostic tests were included. Patients with no temporal bone imaging studies were excluded. Eighteen children were included in this study; 13 children (72%) were male, and the mean (median; range) age of patients at the time of inner ear imaging studies was 2 years (4.5 years; 8 months to 8 years). Coloboma was present in 13 patients (72%) and choanal atresia in 5 (28%); semicircular canal anomalies were present in all patients. Additionally, 13 patients (72%) were diagnosed as having hindbrain anomalies, 17 (94%) as having endocrine disorders, 17 (94%) as having mediastinal organ malformations, and all as having middle or external ear abnormalities and development delay. Cleft lip and cleft palate were found in 6 of 14 patients (43%) who did not have choanal atresia. We tested 16 patients for mutations in the CHD7 gene; 10 were positive (63%) for mutations, 4 (25%) were negative, and 2 (13%) were inconclusive. Semicircular canal anomalies were the most consistent finding in our patients with CHARGE syndrome. Given the high prevalence of semicircular canal hypoplasia and importance of imaging for diagnosing CHARGE syndrome, we propose changing the term CHARGE syndrome to 3C syndrome to emphasize the importance of the semicircular canals and to recall the 3 major criteria for diagnosis: coloboma, choanal atresia, and semicircular canal anomaly. The nomenclature would also reference the 3 semicircular canals in each ear. This new name for CHARGE syndrome would provide a mnemonic and focus the disease on the most important clinical criteria for diagnosis.


Characterization of the cysteine protease domain of Semliki Forest virus replicase protein nsP2 by in vitro mutagenesis.
The function of Semliki Forest Virus nsP2 protease was investigated by site-directed mutagenesis. Mutations were introduced in its protease domain, Pro39, and the mutated proteins were expressed in Escherichia coli, purified and their activity in vitro was compared to that of the wild type Pro39. Mutations M781T, A662T and G577R, found in temperature-sensitive virus strains, rendered the enzyme temperature-sensitive in vitro as well. Five conserved residues were required for the proteolytic activity of Pro39. Changes affecting Cys478, His548, and Trp549 resulted in complete inactivation of the enzyme, whereas the replacements N600D and N605D significantly impaired its activity. The importance of Trp549 for the proteolytic cleavage specificity is discussed and a new structural motif involved in substrate recognition by cysteine proteases is proposed.


Experimental evidence for a partially dissociated water bilayer on Ru[0001].
Core-level photoelectron spectra, in excellent agreement with ab initio calculations, confirm that the stable wetting layer of water on Ru[0001] contains O-H and H2O in roughly 3:5 proportion, for OHx coverages between 0.25 and 0.7 ML, and T<170 K. Proton disorder explains why the wetting structure looks to low energy electron diffraction (LEED) to be an ordered p(square root of 3 x square root of 3)R30 degrees adlayer, even though approximately 3/8 of its molecules are dissociated. Complete dissociation to atomic oxygen starts near 190 K. Low photon flux in the synchrotron experiments ensured that the diagnosis of the nature of the wetting structure quantified by LEED is free of beam-induced damage.


The phytoestrogen genistein prevents trabecular bone loss and affects thyroid follicular cells in a male rat model of osteoporosis.
As a major phytoestrogen of soy, genistein effectively prevents bone loss in both humans and rat models of osteoporosis. However, although the bone-sparing effects of genistein are achieved directly through estrogen receptors, its mode of action on bone by modulation of other endocrine functions is not entirely clear. Thus, thyroid hormones and calcitonin (CT) have an essential influence on bone metabolism. Besides its action on bones, in this study we examined the effect of genistein on the activity of two different endocrine cell populations, thyroid follicular and C-cells. Fifteen-month-old Wistar rats were either bilaterally orchidectomized (Orx) or sham-operated (SO). Two weeks after surgery, half of the Orx rats were treated chronically with 30 mg kg-1 b.w. genistein (Orx + G) subcutaneously (s.c.) every day for 3 weeks, while the remaining Orx rats and the SO rats were given the same volume of sterile olive oil to serve as controls. For histomorphometrical analysis of the trabecular bone microarchitecture an ImageJ public domain image processing programme was used. Thyroid sections were analysed histologically and stereologically after visualization of follicular and C-cells by immunohistochemical staining for thyroglobulin and CT. Thyroid follicular epithelium, interstitium, colloid and CT-immunopositive C-cells were examined morphometrically. Serum concentrations of osteocalcin (OC), triiodothyronine (T3 ), thyroxine (T4 ) and CT were determined as well as urinary calcium (Ca2+ ) concentrations. Genistein treatment significantly increased cancellous bone area (B.Ar), trabecular thickness (TbTh) and trabecular number (TbN) (P < 0.05), but trabecular separation (Tb.Sp) was decreased (P < 0.05) compared with control Orx rats. In the thyroid, genistein treatment significantly elevated the relative volume density (Vv) of the follicular cells (P < 0.05) compared with Orx, whereas Vv of the colloid was lower (P < 0.05) than in the Orx. Evaluation of the biochemical parameters showed significant reductions in serum OC, T3 , T4 and urinary Ca2+ concentrations (P < 0.05), compared with Orx rats. These data indicate that genistein treatment improves the trabecular microarchitecture of proximal tibia, induces histomorphometrical changes in thyroid glands, and decreases circulating thyroid hormone levels in orchidectomized rat model of male osteoporosis.