In vitro and in vivo study of 99mTc-MIBI encapsulated in PEG-liposomes: a promising radiotracer for tumour imaging.
Encapsulation of technetium-99m sestamibi ((99m)Tc-MIBI) in polyethyleneglycol-liposomes ((99m)Tc-MIBI-PEG-liposomes) could extend the duration of its circulation in blood and alter its biodistribution, enabling its concentration in tumours to be increased. An original method to encapsulate (99m)Tc-MIBI in PEG-liposomes is described. The (99m)Tc-MIBI-PEG-liposomes were compared with free (99m)Tc-MIBI with respect to (a) tumour availability (b) ability to distinguish between chemotherapy-sensitive and -resistant cells and (c) uptake ratio in tumour imaging. PEG-liposomal systems composed of distearoylphosphatidylcholine/cholesterol/PEG(2000)-distearoyl phosphatidylethanolamine and lissamine-rhodamine B-labelled liposomes were used. The encapsulation of (99m)Tc-MIBI in liposomes was achieved using the K(+) diffusion potential method. We compared the uptake of free versus encapsulated (99m)Tc-MIBI by sensitive and resistant erythroleukaemia (K562) and breast tumour (MCF-7ras) cells. To assess the internalisation of these liposomes into cells, rhodamine B-labelled PEG-liposomes were used and visualised by fluorescence microscopy. Biodistribution and imaging characteristics of encapsulated and free radiotracer were determined in rats and tumour-bearing nude mice. The efficiency of (99m)Tc-MIBI encapsulation in PEG-liposomes was 50+/-5%. Use of (99m)Tc-MIBI-PEG-liposomes did not impair the ability of this tracer to distinguish between chemotherapy-sensitive and -resistant tumour cells; the percentage of radioactivity accumulated in the sensitive K562 cells was 1.24+/-0.04%, as compared with 0.41+/-0.04% in the resistant K562 cells. One hour post injection in rats, PEG-liposomes showed a ten times higher activity in blood than free (99m)Tc-MIBI, whereas activity of free (99m)Tc-MIBI in kidneys and bladder was markedly higher than that of encapsulated (99m)Tc-MIBI, indicating faster clearance of the free radiotracer. In the (MCF7-ras)-bearing nude mice, PEG-liposome uptake in tumour was two times that of free (99m)Tc-MIBI. Summarising, the (99m)Tc-MIBI-PEG-liposomes demonstrated a longer blood circulation time, enabled distinction between chemotherapy-sensitive and -resistant cells and improved tumour to background contrast in in vivo imaging. (99m)Tc-MIBI-PEG-liposomes therefore show promising potential for tumour imaging.


Jarvik 2000 axial-flow ventricular assist device placement to a systemic morphologic right ventricle in congenitally corrected transposition of the great arteries.
Few descriptions of the implantation and management of an implantable ventricular assist device in patients with complex congenital heart disease exist in the literature. The Jarvik 2000 axial-flow ventricular assist device (Jarvik Heart, Inc., NYC, NY, USA) can be placed in either the left or the right ventricle. We present the case of a 60-year-old man with congenitally corrected transposition of the great arteries who underwent successful placement of a Jarvik 2000 axial-flow ventricular assist device in a systemic morphologic right ventricle.


Accepting responsibility for long-term care--a paradox in times of a global nursing shortage?
Need for long-term care (LTC) is increasing globally, and nurses have a professional imperative to address the growing need for long-term care (LTC). The author reviews the effect of globalization and the epidemiologic transition upon the growing need for LTC. I also summarize the lessons learned in the developing world, as well as in the industrialized world, based on the existing research evidence. The purpose of this paper is to explain the need for nursing as a profession to accept responsibility for LTC as part of nursing's raison d'etre, despite the global nursing shortage. This includes responsibility for innovative policy, health service, practice, research, nursing education development, and health promotion, because prevention is key to slowing the steep increase in LTC needs. Nurses must develop strategies for clinical practice, management, education, and research in order to increase our ability to meet future needs for LTC.


Comparative immuno-Cerenkov luminescence and -PET imaging enables detection of PSMA+ tumors in mice using 64Cu-radiolabeled monoclonal antibodies.
Here, we describe immuno-Cerenkov luminescence imaging (immuno-CLI) with a specific monoclonal antibody-based tracer for the detection of prostate tumors, which is used in preclinical positron emission tomography (PET) imaging. As PET isotopes generate a continuous spectrum of light in the ultraviolet/visible (UV/vis) wavelength range (Cerenkov luminescence, CL) in dielectric materials and consequently inside living tissues, these isotopes can also be detected by luminescence imaging performed with optical imaging (OI) systems. Imaging tumors with tracers that are specifically binding to a tumor-associated antigen can increase diagnostic accuracy, enables monitoring of treatment efficacy, and can be advantageous compared to radiolabeled small molecules used in PET-oncology such as 2-deoxy-2-[18F]-fluoro-D-glucose ([18F]FDG; glucose metabolism) or [11C]choline (membrane synthesis) which was used to image prostate cancer. In this study, we compared on three consecutive days immuno-CLI and -PET of the applied 64Cu-labeled and well described monoclonal antibody 3/F11 in prostate-specific membrane antigen (PSMA)-positive (C4-2, PSMA+) and -negative (DU 145, PSMA-) prostate tumor xenografts, inoculated in SCID mice. In vivo immuno-CLI and -PET measurements demonstrated linear correlation of both modalities, in line with ex vivo analysis performed with CLI and γ-counting. As CLI is also able to trace radioisotopes used for theranostic approaches, immuno-CLI could be an interesting, low-cost imaging alternative to immuno-PET.


Tat protein vaccination of cynomolgus macaques influences SHIV-89.6P cy243 epitope variability.
In a previous study we showed that vaccination with the native Tat protein controlled virus replication in five out of seven monkeys against challenge with the simian human immunodeficiency virus (SHIV)-89.6P cy243 and that this protection correlated with T helper (Th)-1 response and cytotoxic T lymphocyte (CTL) activity. To address the evolution of the SHIV-89.6P cy243 both in control and vaccinated infected monkeys, the sequence of the human immunodeficiency virus (HIV)-1 Tat protein and the C2-V3 Env region of the proviral-DNA-derived clones were analyzed in both control and vaccinated but unprotected animals. We also performed analysis of the T cell epitope using a predictive epitope model taking into consideration the phylogeny of the variants. Our results suggest that even though the viral evolution observed in both groups of monkeys was directed toward variations in the major histocompatibility complex (MHC)-I epitopes, in the control animals it was associated with mutational escape of such epitopes. On the contrary, it is possible that viral evolution in the vaccinated monkeys was linked to mutations that arose to keep high the viral fitness. In the vaccinated animals the reduction of epitope variability, obtained prompting the immune system by vaccination and inducing a specific immunological response against virus, was able to reduce the emergence of escape mutants. Thus the intervention of host's selective forces in driving CTL escape mutants and in modulating viral fitness appeared to be different in the two groups of monkeys. We concluded that in the vaccinated unprotected animals, vaccination with the Tat protein induced a broad antiviral response, as demonstrated by the reduced ability to develop escape mutants, which is known to help in the control of viral replication.


N-methyl-D-aspartate receptor blockade inhibits estrogenic support of dendritic growth in a sexually dimorphic rat spinal nucleus.
The lumbar spinal cord of rats contains the sexually dimorphic, steroid-sensitive spinal nucleus of the bulbocavernosus (SNB). Dendritic development of SNB motoneurons requires the action of both androgens and estrogens. Estrogenic effects are limited to the initial growth of SNB dendrites through 4 weeks of age. During this postnatal period, dendritic growth in other spinal motoneurons is regulated by N-methyl-D-aspartate (NMDA) receptor activation. In this study, we tested whether NMDA receptor activation was involved in SNB dendritic growth and whether the estrogenic support of SNB dendritic growth was dependent on the activation of NMDA receptors. Motoneuron morphology was assessed in normal males, intact males treated daily with the NMDA receptor antagonist MK-801, castrated males treated with estradiol benzoate (EB), and castrated males treated with both EB and MK-801. SNB motoneurons were retrogradely labeled with cholera toxin-horseradish peroxidase at 4 weeks of age (when dendritic length is normally maximal) and reconstructed in three dimensions. Somal area and dendritic length of SNB motoneurons in MK-801-treated, intact males were below those of normal males. Dendritic growth was partially supported in EB-treated castrates, but this growth was blocked by MK-801 treatment. These results suggest that, as in other motoneurons, dendritic development in the SNB involves NMDA receptors and, furthermore, that the estrogen-sensitive component of SNB dendritic development requires their activation.


[Bipolar luxation of the clavicle. A case report].
The author reports a case of traumatic bipolar dislocation of the clavicle. This very rare lesion was first described by Porral in 1831. Since that time the number of new observations is very small and the treatment remains controversial. Because of his age, our patient was treated by a closed method: immobilization in a figure of 8 bandage after reduction by manipulation. The final functional result was good.


Effects of moderate doses of alcohol on immediate recall of numbers: some implications for information technology.
Moderate doses of alcohol will have detrimental effects on memory functions used in various aspects of human interaction with information technology. The need to deal with multidigit numbers while under alcohol intoxication (e.g., making telephone calls) is a reality of life. To determine these relations, the effects of alcohol on immediate ordered recall were studied in a practical number-dialing task. Immediate ordered recall of eight-digit numbers, presented visually or auditorily, was tested in read-and-dial or listen-and-dial forced ordered recall tasks with male subjects (N = 11) under two levels of blood alcohol concentration (BrAC = 0.05% and BrAC = 0.1%) and a no-alcohol placebo control condition (BrAC = 0.0%). With increasing alcohol level, immediate ordered recall of whole numbers (all eight digits correct and in the right order) fell by 9% (visual presentation) and 15% (auditory presentation). No significant interaction effect between alcohol level and digit position in the number was found for visually presented numbers, while a weak, but significant, effect was found for auditorily presented numbers (most prominent at digit positions 5, 6 and 7). This is probably due to the difference in rehearsal opportunities in the two presentation modes. No significant interaction effects between alcohol level and presentation modality were found. The results, tailored to a practical everyday task of dialing unfamiliar eight-digit telephone numbers, show that even moderate doses of alcohol will affect the performance of an already fragile short-term memory system engaged whenever reproduction of digit strings is required.


Involvement of P2X7 receptors in retinal ganglion cell apoptosis induced by activated Müller cells.
Müller cell reactivation (gliosis) is an early response in glaucomatous retina. Previous studies have demonstrated that activation of P2X7 receptors results in retinal ganglion cell (RGC) apoptosis. Here, the issues of whether and how activated Müller cells may contribute to RGC apoptosis through P2X7 receptors were investigated. Either intravitreal injection of (S)-3,5-dihydroxyphenylglycine (DHPG), a group I metabotropic glutamate receptor (mGluR I) agonist, in normal rat retinas, or DHPG treatment of purified cultured rat retinal Müller cells induced an increase in glial fibrillary acidic protein (GFAP) expression, indicative of Müller cell gliosis. In addition, an increase in adenosine triphosphate (ATP) release from purified cultured Müller cells was detected during DHPG treatment (for 10 min to 48 h), which was mediated by the intracellular mGluR5/Gq/PI-PLC/PKC signaling pathway. Intravitreal injection of DHPG mimicked the reduction in the number of fluorogold retrogradely labeled RGCs in chronic ocular hypertension (COH) rats. Treatment with the conditioned culture medium (CM) obtained from the DHPG-activated Müller cell medium induced an increase in the number of TUNEL-positive cells in cultured RGCs, which was mimicked by benzoylbenzoyl adenosine triphosphate (BzATP), a P2X7 receptor agonist, but was partially blocked by brilliant blue G (BBG), a P2X7 receptor antagonist. Moreover, the CM treatment of cultured RGCs significantly increased Bax protein level and decreased Bcl-2 protein level, which was also mimicked by BzATP and partially blocked by BBG, respectively. These results suggest that reactivated Müller cells may release excessive ATP, in turn leading to RGC apoptosis through activating P2X7 receptors in these cells.


Continuous intravenous dosing with ciprostene using a portable pump in ambulatory patients.
Parenteral compounds present special drug delivery challenges. This open-label study evaluated a portable infusion pump as a means to deliver intravenous ciprostene, a stable prostacyclin analog. Ten patients with peripheral vascular disease and claudication received ciprostene (titrated to 120 ng/kg/min) infused over 8 hours 1 day per week for 4 consecutive weeks. Patients successfully maintained the pump strapped to the waist. The mean +/- standard deviation delivery error, with volumes of 6 to 10 mL over 8 hours, was -0.895 +/- 3.177%. Accordingly, the pump performed well with a potent drug under these clinical conditions. Headache, flushing, and infusion site irritation during infusion were the most frequent side effects. Blood pressure remained unchanged during infusion; however, heart rate increased significantly (P < .05, maximum increase was 13.9 +/- 2.1 beats per minute [mean +/- standard error of the mean]. Mean (+/- standard error of the mean) relative claudication times on treadmill remained unchanged; however, absolute claudication times increased (P < .05) from 6.6 +/- 1.8 to 10.0 +/- 2.2 minutes. Ciprostene inhibited adenosine diphosphate-induced platelet aggregation by 56.0 +/- 12.7% (mean +/- standard error of the mean). Mean template bleeding times and plasma concentrations of platelet-specific proteins (beta-thromboglobulin, platelet factor 4) did not change.


Is the self-reported private health insurance status in the National Health Survey representative of private health insurance coverage in Australia?
This study determines whether the distribution of self-reported private health insurance (PHI) status in the 2004/05 National Health Survey (NHS) is representative of PHI coverage in Australia. Weighted estimates from the NHS 2004/05 are compared with PHI status reported for 2004/05 by the Private Health Insurance Administration Council (PHIAC, the independent regulator of the private health insurance industry). PHI status was imputed to children in the NHS based on PHI status of the adult in the household. The two data sources were deemed to be different if the PHIAC results were not within the 95% CI range for the NHS estimate. PHI status reported in the NHS and PHIAC are generally comparable except for some categories such as hospital cover of males aged 5-9 years and females aged 85 years and older where the NHS estimates are below PHIAC numbers; and males aged 25-29, 35-39, and 50-54 years where the NHS estimates are higher. The findings suggest that while the NHS 2004/05 estimates may accurately represent coverage in Australia particularly when examined at an aggregated level, there is some variation in the NHS estimates when examined by sex and age group. Researchers need to be aware of the potential for sampling and reporting bias to contribute to some misrepresentation of PHI status when using the NHS to generalise to the Australian population. Exploring corrective measures will ensure that the NHS continues to be a valuable data resource for health researchers in Australia.


[Team Care and Patient Safety].
The purpose of patient safety management is to nurture an environment which provides optimal care for each patient through the cooperation of each healthcare staff member based on the idea of team care. This is based on the safety culture of an organization that places value on sharing information. Laboratory medicine is expected to become more important in the areas of staff, patient, and community education.


Open-field emotional reactivity and alcohol intake in rats.
The relationship between open-field emotional reactivity and alcohol intake was investigated. Randomly selected, high and low open-field defecation (OFD) groups from each of the MNR, MR and RCA genetic lines of rats were used. No functional relation between OFD as a measure of emotional reactivity and alcohol intake was found. Differences in alcohol intake among genetic lines were confirmed. It is concluded that emotional reactivity is a mediating process related independently to both OFD and alcohol intake.


Grading system for lymph vessel tumor emboli: significant outcome predictor for invasive ductal carcinoma of the breast.
The purpose of this study was to confirm that the grading system for lymph vessel tumor emboli is a significant histologic outcome predictor for patients with invasive ductal carcinoma. The subjects of this study were 1042 invasive ductal carcinoma patients who did not receive neoadjuvant therapy. We classified all invasive ductal carcinomas according to the grading system for lymph vessel tumor emboli we devised, and performed multivariate analyses with well-known prognostic factors. Of 1042 carcinomas, 666, 250, 97, and 29 were classified according to the grading system for lymph vessel tumor emboli as grade 0 (no lymph vessel invasion), grade 1, grade 2, and grade 3, respectively. The univariate analyses showed that the difference in outcome between the group with grade 0 and the group with grade 1 was not significant, but that survival time was significantly shorter in the group of patients with grade 2 carcinomas than in the group with grade 1 carcinomas and significantly shorter in the group of patients with grade 3 carcinomas than in the group with grade 2 carcinomas. Multivariate analyses demonstrated that having a grade 2 or grade 3 carcinoma significantly increased the hazard rates for tumor recurrence and tumor-related death in the patients as a whole as well as in both the group of patients with nodal metastasis and the group without nodal metastasis. The grading system for lymph vessel tumor emboli is an excellent histologic grading system for predicting the outcome of patients with invasive ductal carcinoma of the breast.


Active intestinal secretion of the fluoroquinolone antibacterials ciprofloxacin, norfloxacin and pefloxacin; a common secretory pathway?
The transepithelial transport of three fluoroquinolones, norfloxacin, ciprofloxacin and pefloxacin has been compared by using cultured human intestinal Caco-2 cell-layers. Absorptive (apical-basal) fluxes of ciprofloxacin and norfloxacin are small relative to basal to apical fluxes. Norfloxacin and ciprofloxacin are thus subject to active transepithelial secretion. Active net secretion of norfloxacin displays saturation kinetics with Vmax and Km values of 36.2 +/- 6.9 nmol.cm-2.hr-1 and 1.42 +/- 0.79 mM. In contrast, transepithelial pefloxacin fluxes are large, show marked saturation while the direction of net flux is variable and small relative to transepithelial fluxes. Norfloxacin, pefloxacin and ciprofloxacin are all subject to accumulative transport across the basal surface of Caco-2 cell layers. A number of 4-quinolones and fluoroquinolones are capable of inhibition of both net secretion of ciprofloxacin and cellular accumulation across the basal-lateral cell surface. Cinoxacin, a 4-quinolone may selectively inhibit exit from the cell across the apical membrane. Cross-competition studies suggest that fluoroquinolones may compete for a common carrier at the basal-lateral membrane. It is likely that the mechanism of transepithelial secretion involves a common accumulative transport at the basal-lateral membrane followed by facilitated exist across the apical membrane. Pefloxacin may interact with a brush-border carrier for which norfloxacin and ciprofloxacin are poor substrates, enhancing the absorptive flux of this fluoroquinolone.


Annular pancreas in an adult managed by laparobotic surgery: a case report.
Annular pancreas in an adult is an uncommon and infrequently reported anomaly which is characterized by the presence of ectopic pancreatic tissue surrounding the descending part of the duodenum. It is one of the few congenital anomalies of the gastrointestinal tract, which can manifest with symptoms late in life (Ravitch and Woods in Ann Surg 132:1116-1127, 1950). In adults, the factors initiating symptoms are recurrent pancreatitis, duodenal stenosis at the site of the annulus, or duodenal or gastric ulceration (Morrell and Keynes in Br J Surg 57:814-816, 1970). Operative management of these cases involves bypassing the obstructed duodenum. Duodenoduodenostomy is routinely performed in neonates and children. We report a case of annular pancreas in a 55-year-old male that was successfully treated with robotic duodenoduodenostomy.


Intensive care delirium monitoring and standardised treatment: a complete survey of Dutch Intensive Care Units.
Delirium is a frequent and serious problem in the Intensive Care Unit (ICU). Several international guidelines recommend daily monitoring for ICU-delirium. The purpose of this article is to give an up-to-date overview of the current status of monitoring and treatment of ICU-delirium in the Netherlands. Nation-wide, telephone-based questionnaire survey. Head nurse of all ICUs and a random sample of intensivists. Only 14% (n=14) of all Dutch ICUs (n=103) monitored for ICU-delirium. Of these, only half (7%) used a tool that is validated in ICU patients. In 31% of Dutch ICUs, a protocol was used to treat ICU-delirium. Responses were obtained from 100% of ICUs. Despite an international guideline, not more than 7% of ICUs in our study routinely evaluated the presence of delirium with a validated instrument. Fewer than one-third of Dutch ICUs use a protocol to treat ICU-delirium.


Outcomes of patients admitted to the intensive care unit with idiopathic pulmonary fibrosis.
To evaluate outcomes of patients admitted to an intensive care unit with idiopathic pulmonary fibrosis (IPF) and acute respiratory deterioration. Retrospective cohort study. University-affiliated, tertiary adult ICU. All patients admitted to the ICU between January 1996 and December 2006 with an established diagnosis of IPF were identified from review of case notes, ICU charts and electronic hospital records. Patient demographics, ICU investigation and treatment profiles were characterised; final follow-up was electronically from the State Registry. Primary study end-point was survival from ICU admission until December 2007; secondary end-points were survival from diagnosis and from first respiratory hospital admission. 24 patients were identified with IPF, diagnosed by lung biopsy (8) and by clinical criteria; 21 patients were admitted with acute respiratory failure, and three postoperatively. Mean age was 66 (SD, 16) years, mean APACHE III score was 82 (SD, 37), and 14 were men. Admission diagnoses were acute exacerbation of IPF (8), pneumonia (10), acute heart failure (3) and postoperative (3). All patients received broad-spectrum antibiotics, and 17 continued to receive corticosteroids prescribed previously. Nineteen patients were mechanically ventilated for a mean of 19.1 days (SD, 25.3); 13 of 19 patients had non-invasive ventilation before mechanical ventilation, and four received only non-invasive ventilation. Sixteen mechanically ventilated patients died in the ICU, another six died in hospital (2-30 days after ICU discharge); and two were discharged home. Median survival (95% CI) was 16 (9-19) days from ICU admission; 55 (18-284) days from first respiratory admission; and 1.05 (0.34-1.75) years from IPF diagnosis. Outcomes of patients with IPF admitted to the ICU are poor. Indications for mechanical ventilation appear uncertain.


H(2) sensing characteristics of SnO(2) coated single wall carbon nanotube network sensors.
SnO(2) nanoparticle coated single wall nanotube (SWNT) network sensors were fabricated by forming a SWNT network on the Pt patterned SiO(2)/Si substrate using a dip coating method and subsequently depositing SnO(2) nanoparticles on the SWNT network by rf magnetron sputtering. Their H(2) gas sensing properties were investigated. The SnO(2)-SWNT network sensors stably and reversibly responded to H(2) gas even at room temperature and could detect H(2) gas down to 100 ppm. In addition to the low temperature detection, a remarkable finding was that the gas sensing behavior of SnO(2)-SWNT network sensors was changed from p-type to n-type with increasing SnO(2) deposition time (i.e. surface coverage of SnO(2) on SWNT). A schematic model was proposed to explain the switching of sensing behavior depending on the surface coverage of SnO(2) nanoparticles on the SWNTs.


The Arg633His substitution responsible for the private platelet antigen Gro(a) unravelled by SSCP analysis and direct sequencing.
We have previously described the private or family platelet antigen, Gro(a), which was identified in a case of neonatal alloimmune thrombocytopenia. The Gro(a) antigen was found to be located on the GP IIIa (beta3) subunit of the GP IIb/IIIa complex, the most prominent fibrinogen receptor of platelets. Initial experiments to characterize the Gro(a) antigen at the molecular genetic level were unsuccessful. We therefore decided to use a different strategy to unravel the molecular basis of this antigen. Platelet GP IIIa mRNA of a Gro(a+) and a Gro(a-) donor was amplified with suitable primers in a reverse transcriptase-polymerase chain reaction (RT-PCR) and subjected to single-strand conformational polymorphism (SSCP) analysis. Three regions of the amplified GP IIIa cDNA derived from the Gro(a+) donor showed a different SSCP pattern when compared to that of the Gro(a-) donor. Direct nucleotide sequence analysis of these three segments revealed that two of them contained silent substitutions, A1163C, A1553G and G1565A. The first and the latter changes were described previously. In the third segment a G1996A mutation was found, predicting an arginine --> histidine substitution at position 633 of the mature glycoprotein. PCR-ASRA (allele-specific restriction enzyme analysis) performed on cDNA as well as on genomic DNA with the restriction enzyme MaeIII showed that the His633 form of GPIIIa is restricted to the Gro(a+) phenotype. The observed mutation is three amino acids upstream of the mutation underlying the HPA-8/Sr system (Arg636Cys), suggesting this region of GP IIIa to be susceptible for mutations. Moreover, the presence of a silent mutation and two low-frequency forms of the silent polymorphisms strongly suggests that the G1996A mutation did not occur in a direct ancestral allele.


Psychosocial dysfunction in the first year after Guillain-Barré syndrome.
In this investigation we study the impact of Guillain-Barré syndrome (GBS) on psychological distress, depressive symptoms, and health status of patients during the first year after GBS. At 3, 6, and 12 months, patients were given the General Health Questionnaire, the Sickness Impact Profile, and the Center for Epidemiologic Studies Depression Scale. Eighty-five patients participated. Psychological distress and depressive symptoms were present but improved between 3 and 6 months. At 12 months the psychosocial health status was still impaired. Patients who perceived their physical residua to be moderately to seriously disruptive and patients with muscle ache and cramps had worse scores on all scales. It can be concluded that most of the improvement occurred in the first 6 months. Psychosocial health status, however, was still impaired at 1 year, but depressive symptoms played no role. Treatment of muscle ache and cramps, and the disruptive effect of physical residua should be seriously considered.


Rotation and decentration of an undersized plate-haptic trifocal toric intraocular lens in an eye with moderate myopia.
We present the case of a 56-year-old woman with moderate myopia and bilateral cataract who had cataract extraction and intraocular lens (IOL) implantation. Due to the patient's desire for spectacle independence, a trifocal IOL with toric correction for astigmatism was implanted. During the follow-up, it became obvious that the implanted IOL had rotated and tilted due to insufficient fixation in the large capsular bag of the myopic eye. An IOL explantation was therefore performed, and the original IOL was exchanged for a bifocal toric IOL with a larger overall diameter. Stable fixation of the IOL in the capsular bag was achieved, and after surgery in the second eye, the patient recovered good bilateral vision. This case illustrates the need for careful selection of IOL diameter and sizing even in patients with moderate myopia due to the potentially larger ocular dimensions in these patients.


Are 3 sentinel nodes sufficient?
It has recently been proposed that only 3 sentinel lymph nodes (SLNs) are required for an adequate SLN biopsy. Others have advocated removing all nodes that are blue, hot, at the end of a blue lymphatic channel, or palpably suspicious or that have radioactive counts of 10% or greater of the most radioactive SLN. Our objective was to determine the false-negative rate (FNR) associated with limiting SLN biopsy to 3 nodes. Multicenter prospective study. Both academic and private practice. A total of 4131 patients underwent SLN biopsy followed by completion axillary node dissection. The FNR associated with 3-node SLN biopsy. Of the 4131 patients in this study, an SLN was identified in 3882 (94.0%). The median number of SLNs identified was 2; more than 3 SLNs were removed in 738 patients (17.9%). Of the patients in whom a SLN was identified, 1358 (35.0%) were node positive. The overall FNR in this study was 7.7%. In 89.7% of node-positive patients, a positive SLN was found in the first 3 SLNs removed. If SLN biopsy had been limited to the first 3 nodes, the FNR would be 10.3% (P = .005 compared with removing >3 SLNs). The FNR increased with the strategy of limiting SLN biopsy to fewer SLNs (P<.001). Removing only 3 SLNs cannot be recommended, because it is associated with a substantially increased FNR.


[Bone and bone-muscle autoplasty in the treatment of chronic osteomyelitis].
Osseous autoplasty of osteomyelitic cavities was used in 138 patients with different forms of chronic osteomyelitis. Complications were found in 8 patients. These patients had suppurations of the wound with sequestrations of osseous transplants.


Organizational justice and stress: the mediating role of work-family conflict.
This study examined the relationship between organizational justice and stress and whether work-family conflict was a mediator of the relationship. Distributive, procedural, interpersonal, and informational injustice were cast as stressors to explore their relationships with the stress levels of 174 faculty members employed at 23 U.S. universities. The results revealed that procedural and interpersonal justice had the strongest relationships with stress, and that these effects were mediated by work-family conflict. The presence of justice seemed to allow participants to better manage the interface of their work and family lives, which was associated with lower stress levels. These results were observed even when controlling for job satisfaction and the presence of organizational work-family policies.


[Recurrent hematuria in children].
Twenty-three children with recurrent macroscopic hematuria have been observed. Six children presented with glomerular disorder with mesangial deposits of IgG and IgA (Berger's disease). The hematuria episodes occurred in the 48 hours following an infection, more often respiratory. Renal functions were not impaired. On light microscopy, glomerular lesions were minimal, or were lesions of focal and segmental glomerulonephritis. Ten children seemed to have hereditary nephritis. In 5 cases, nephritis was accompanied by deafness (Alport's syndrome). In 5, nephritis was hereditary but isolated. The electron microscopy examination of basement membranes showed lesions consistent with Alport's syndrome. In cases of hereditary nephritis without deafness, basement membranes were less impaired. In 7 children, no specific etiology was found.


Use of infrared thermal imaging to isolate Arabidopsis mutants defective in stomatal regulation.
In response to drought, plants synthesise the hormone abscisic acid (ABA), which triggers closure of the stomatal pores. This process is vital for plants to conserve water by reducing transpirational water loss. Moreover, recent studies have demonstrated the advantages of the Arabidopsis stomatal guard cell for combining genetic, molecular and biophysical approaches to characterise ABA action. However, genetic dissection of stomatal regulation has been limited by the difficulty of identifying a reliable phenotype for mutant screening. Leaf temperature can be used as an indicator to detect mutants with altered stomatal control, since transpiration causes leaf cooling. In this study, we optimised experimental conditions under which individual Arabidopsis plants with altered stomatal responses to drought can be identified by infrared thermography. These conditions were then used to perform a pilot screen for mutants that displayed a reduced ability to close their stomata and hence appeared colder than the wild type. Some of the mutants recovered were deficient in ABA accumulation, and corresponded to alleles of the ABA biosynthesis loci ABA1, ABA2 and ABA3. Interestingly, two of these novel aba2 alleles were able to intragenically complement the aba2-1 mutation. The remaining mutants showed reduced ABA responsiveness in guard cells. In addition to the previously known abi1-1 mutation, we isolated mutations at two novel loci designated as OST1 (OPEN STOMATA 1) and OST2. Remarkably, ost1 and ost2 represent, to our knowledge, the first Arabidopsis mutations altering ABA responsiveness in stomata and not in seeds.


The regulation of glucose transporter gene expression by cyclic adenosine monophosphate in NIH3T3 fibroblasts.
The effect of cAMP on glucose transport was studied in fibroblastic cells. Incubation of confluent NIH3T3 cells for 6 h in the presence of cholera toxin (10 ng/ml) and 3-isobutyl-1-methylxanthine [(IBMX) 0.2 mM] or 8-bromo-cAMP (0.3 mM) and IBMX resulted in a 4-fold increase in the rate of deoxyglucose uptake; no change in hexose transport could be detected after treatment for 30 min. Either cholera toxin (0.3 ng/ml-30 ng/ml) or 8-bromo-cAMP (30 microM-3 mM) increased the expression of the mRNA encoding the glucose transporter (GT) protein, as determined by hybridization of size-fractionated total RNA to a rat brain GT cDNA. Activation of adenylate cyclase by forskolin also rapidly induced a 4- to 10-fold increase in GT mRNA. The rise in the level of GT mRNA was maximal 3-4 h after addition of the drug, and returned to basal values by 16 h. The stimulation was concentration dependent, with forskolin producing a maximal effect at 30 microM. The effect of a submaximal concentration (1 microM) of forskolin was greatly enhanced in the presence of IBMX (0.2 mM), which alone had little effect on GT mRNA levels. The forskolin-stimulated increase in GT mRNA was not blocked by inhibition of protein synthesis by cycloheximide (10 micrograms/ml) or anisomycin (100 microM). The involvement of GT gene transcription was assessed by the nuclear run-on assay. Treatment of the cells with 30 microM forskolin increased transcription 10-fold within 30 min; the activation was not blocked by cycloheximide.(ABSTRACT TRUNCATED AT 250 WORDS)


Textmania: text messaging during the manic phase of bipolar I disorder.
Advancements in modern technology have brought tremendous changes in human behavior. One such change is in modes of communication such as text messaging, or texting. This form of communication has emerged as one of the dominant modes of communication in the world. This report presents a differential pattern of texting seen during the manic episode of a young adult with bipolar I disorder. We observed all the DSM IV manic symptoms; interestingly the patient's predominant medium for communication was texting. The patient reported a dramatic increase in the quantity of both texting and sex-texting (or sexting) in addition to a decrease in quality of the message content. In addition, there was a substantial increase in the number of people with whom the patient engaged in simultaneous texting conversations. This case provides evidence for the need to consider non-traditional forms of communication when evaluating a patient's communication pattern during mania.


A Pilot RCT Investigating the Effects of Targeted Compression on Athletes With Pelvic/Groin Pain.
Athletic pelvic/groin pain is a common yet often challenging problem to both diagnose and manage. A new tool has been developed based on the clinical effects of applied force on the pelvis. Early findings indicate that this customized compression orthosis may have a positive effect on pelvic/groin pain and performance measures. To inform the design and test the practicality of procedures for a future definitively powered randomized controlled trial and to provide an estimate of the effect size of this orthosis on selected clinical and performance measures. Pilot randomized controlled trial with participants randomly allocated to an intervention or waiting-list control group. The training location of each athlete. 24 athletes with subacute and chronic pelvic conditions were proposed to be recruited. A customized compression orthosis, delivering targeted compression to the pelvic girdle. Measures were the active straight leg raise (ASLR) test, squeeze test, broad jump, and the multiple single-leg hop-stabilization test. A total of 16 athletes completed the study. The invention group demonstrated moderate to large estimated effect sizes on the squeeze test and active straight leg raise tests (d = 0.6-1.1) while wearing the orthosis. Small effect sizes (d = 0.2) were seen on jump distance and the dominant leg balance score. Compared with the control group, the intervention group also showed moderate to large estimated effect sizes on the active straight leg raise measures (d = 0.5-0.9) when wearing sports shorts. The protocol was feasible. Effect sizes and recruitment/attrition rates suggest that the intervention holds promise and that a future definitively powered randomized controlled trial appears feasible and is indicated.


Reactions of alkenes with ozone in the gas phase: a matrix-isolation study of secondary ozonides and carbonyl-containing reaction products.
Gas phase ozonolysis reactions of the alkenes ethene, cis- and trans-but-2-ene, isoprene and the monoterpenes alpha-pinene, beta-pinene, beta-carene, limonene and beta-myrcene have been carried out and the reaction products have been trapped in O2-doped-argon matrices onto a Csl window held at 12 K. Products have been identified by IR spectroscopy. Comparison with previous matrix spectra, where secondary ozonides have been generated either in situ by annealing or in solution reactions allows a positive identification of the secondary ozonides of ethene and of cis- and trans-but-2-ene to be made. These observations are backed up by experiments utilising the isotopes 13C and 2H (D). It appears that secondary ozonides have also been formed from isoprene and the range of monoterpenes studied; this hypothesis is based upon the similarity of spectral features seen in the products of these reactions within those of the simpler alkenes. A number of other primary and secondary products are also identified from these reactions. Ethene gives formaldehyde as a primary product and acetaldehyde as a secondary product; it is found that the yield of acetaldehyde compared to formaldehyde increases as the reaction times are increased. Formaldehyde, one of the expected primary products, is formed by ozonolysis of beta-pinene, although the other expected primary product, nopinone, is not seen. A range of secondary reaction products have been identified from the ozonolysis of the monoterpenes studied.


Induction of functional cytodifferentiation in the epithelium of tissue recombinants. I. Homotypic seminal vesicle recombinants.
Functional cytodifferentiation of seminal vesicle epithelium was investigated in tissue recombinants. Neonatal rat and mouse seminal vesicles were separated into epithelium and mesenchyme using trypsin. Epithelium and mesenchyme were then recombined in vitro to form interspecific rat/mouse homotypic recombinants. Growth as renal grafts in adult male athymic mice resulted in seminal vesicle morphogenesis in 70% of the recombinants (the remaining 30% failed to grow). Functional cytodifferentiation was judged by the expression of the major androgen-dependent secretory proteins characteristic of the seminal vesicles of adult rats and mice. Antibodies specific for each of these proteins were used to screen tissue sections by immunocytochemistry and to probe protein extracts by immunoblotting techniques. The heterospecific recombinants synthesized the full range of seminal vesicle secretory proteins that typifies the species providing the epithelium of the recombinant, not the mesenchyme. There was little functional variation between individual recombinants. The time course of development corresponded to that of intact neonatal seminal vesicles grown under the same conditions. Morphogenesis and functional cytodifferentiation were not evident after one week, but were well advanced after two weeks. Seminal vesicle recombinants grown for three weeks were indistinguishable morphologically and functionally from normal adult seminal vesicles. In addition, the ability of adult seminal vesicle epithelium to be induced to proliferate was examined. In association with neonatal seminal vesicle mesenchyme, the epithelium of the adult seminal vesicle proliferated and retained its normal functional activity. Thus, seminal vesicle functional cytodifferentiation can be faithfully reproduced in homotypic tissue recombinants. The methods used in this study will be used to investigate seminal vesicle development in instructive inductions of heterotypic epithelia.


Effects of delta sleep inducing peptide on sleep cycle of cats deprived of paradoxical sleep.
The effect of synthetic delta sleep inducing peptide (DSIP) on sleep was investigated in cat. DSIP (7 nmol/kg was administered intracerebroventricularly to cats deprived of paradoxical sleep (PS) for 72 h and immediately after termination of PS deprivation an injection of either Ringer or DSIP solution was given. Eight h of recovery sleep was then recorded. DSIP failed to affect the duration of slow-wave sleep, PS and total sleep time. There was, however, significant decrease of wakefulness and light slow-wave sleep (S1) while deep slow-wave sleep (S2) was significantly increased. There was also no change in the latency to the first episode of S2 sleep and PS. Thus, we conclude that DSIP altered the relative amounts of S1 and S2 sleep, causing more S2 (delta) sleep at the time when pressure for sleep was at its highest due to prior sleep deprivation.


Rat muscle 5'-adenylic acid aminohydrolase. Role of K+ and adenylate energy charge in expression of kinetic and regulatory properties.
The kinetic and regulatory properties of homogeneous AMP deaminase from rat skeletal muscle have ben examined with particular emphasis on (a) the role of potassium ions in the expression of these properties and (b) the role of the adenylate energy charge in the regulation of AMP deaminase activity. Although the enzyme has an absolute requirement for K+, the concentration required for maximum activation is dependent on the concentration of substrate. At saturating levels of AMP (greater than or equal 2.0 mM) maximum activation is observed with 25 mM KCl, whereas at lower substrate concentrations (0.2 mM) approximately 50 mM KCl is needed for maximum activation. Conversely, the response of enzyme activity ot increasing levels of substrate is dependent on the level of potassium ions. At substrating concentrations of K+, the saturation curve for AMP is highly sigmoidal (nh=3.2) whereas at higher KCl concentrations, the apparent cooperativity between AMP sites is almost completely abolished (nh=1.5). The inhibition by a number of phosphorylated metabolites, including ATP, GTP, creatine-P, and P1, is likewise sensitive to the concentration of K+. These results suggest that a significant amount of interaction between K+ sites and both substrate and effector sites is required for the expression of the catalytic and regulatory properties of the enzyme. The specific effects of ATP, creatine-P, and P1 on the parameters of Km and Vmax indicate that each of these profile of AMP deaminase activity generated in response to variations in the adenylate energy charge shows that within the physiological range of energy charge (0.75 to 0.95), the activity increases linearly with decreasesing energy charge and is insensitive to both the total adenylate pool size and the presence of P1 and creatine-P. These data suggest that the most important factor in the regulation of AMP deaminase activity is the state of the energy charge rather than the absolute concentrations of the individual effectors.


Sir John Struthers (1823-1899) and his ligament and arcade.
Sir John Struthers, Scottish anatomist, professor, and surgeon, was an early advocate of clinical training in medical education, and his impact is still visible today. He was one of the first prominent anatomists in the United Kingdom to endorse Charles Darwin's controversial theory of natural selection, and his research reflected a desire to illustrate these ideas in cadaveric specimens. Struthers is remembered eponymously for 2 connective tissue condensations in the arm, an arcade and ligament, which may entrap the ulnar and median nerves, respectively. He studied medicine at the University of Edinburgh, received a Doctor of Laws degree from the University of Glasgow, served on the General Medical Council from 1883 to 1891, was president of the Royal College of Surgeons from 1895 to 1897, and was knighted by Queen Victoria in 1898. Struthers' devotion to medical education and insistence on the importance of clinical training laid the foundation for current medical curricula around the world. His observations of sites of potential nerve entrapment in the arm are still taught to neurosurgical trainees today.


Investigation of acetylcholinesterase and mammalian DNA topoisomerases, carbonic anhydrase inhibition profiles, and cytotoxic activity of novel bis(α-aminoalkyl)phosphinic acid derivatives against human breast cancer.
The aim of this study was to evaluate biologically active novel molecules having potentials to be drugs by their antitumor properties and by activities of apoptotic caspase and topoisomerase. Following syntheses of novel eight bis(α-aminoalkyl)phosphinic acid derivatives (4a-h) as a result of array of reactions, compounds were evaluated by cytotoxic effects in vitro on human breast cancer (MCF-7) and normal endothelial (HUVEC) cell lines. All phosphinic acid derivatives were effective for cytotoxicity on both MCF-7 and HUVEC lines, while 4c, 4e, and 4f compounds were found significantly more effective. For the evaluation of antitumor properties of compounds in a highly sensitive method, their effects on inhibiting topoisomerases I and II were investigated. Also, some of the bis(α-aminoalkyl)phosphinic acid derivatives (4a, 4e-h) showed nice inhibitory action against acetylcholinesterase and human carbonic anhydrase isoforms I and II.


Do nonclinical uses of antibiotics make a difference?
An increasing range of antibacterial compounds is being used for nonclinical purposes, especially in the fields of animal husbandry and fish farming. As in human medicine, exposure to antibiotics has lead to the emergence of antibiotic-resistant bacteria in animal populations. The potential impact of antibiotic use in animals on human health and the management of clinical infections in humans is discussed in light of growing evidence to suggest that "new" resistance genes and multiresistant pathogens with increased pathogenicity are emerging in food animals as a direct consequence of antibiotic exposure.


Role of GAP-43 in mediating the responsiveness of cerebellar and precerebellar neurons to axotomy.
To determine whether the competence for axonal sprouting and/or regeneration in the cerebellar system correlates with GAP-43 expression, we have studied GAP-43 mRNA and protein expression in the postlesioned cerebellum and inferior olive. Purkinje cells transiently express GAP-43 during their developmental phase (from E15 to P5 in the rat) which consists of fast axonal growth and the formation of the corticonuclear projection. Adult Purkinje cells, which in control adult rats do not express GAP-43, are extremely resistant to the effects of axotomy but cannot regenerate axons. However, a late and protracted sprouting of axotomized Purkinje cells occurs spontaneously and correlates with a mild expression of GAP-43 mRNA. In contrast, inferior olivary neurons, despite their high constitutive expression of GAP-43, do not sprout but retract their axons and die after axotomy. Furthermore, mature Purkinje cells in cerebellar explants of transgenic mice that overexpress GAP-43 do not regenerate after axotomy, even in the presence of a permissive substrate (cerebellar embryonic tissue) and, contrary to the case in wild-type mice, they do not survive in the in vitro conditions and undergo massive cell death. These results show that the expression of GAP-43 is not only associated with axonal growth, but also with neuronal death.


Contemporaneous severity of symptoms and functioning reflected by variations in reporting doctor-diagnosed osteoarthritis.
Osteoarthritis (OA) is acknowledged as an enduring condition; however, in epidemiologic studies, half of the participants who report having OA at one time may report not having it at a subsequent time. The aim of this study was to examine whether variations in reporting doctor-diagnosed OA reflected concurrent fluctuations in indicators of disease severity in middle-aged women. Data were from 7,623 participants (ages 50-55 years in 2001) in the Australian Longitudinal Study on Women's Health. Based on self-report of doctor-diagnosed OA at surveys in 2001, 2004, 2007, and 2010, the participants were classified according to pattern of OA reporting (e.g., 0-0-0-0 = "no" on all surveys, 0-1-0-1 = "no-yes-no-yes"). Indicators of disease severity included frequency of joint pain/stiffness, use of antiinflammatory medications, and physical functioning assessed with the Short Form 36. Bar graphs were used to show concurrent variations in OA and markers, and associations were examined using log-linear models. In this sample, 46% reported having OA on at least one survey, with half of these cases reporting not having OA at a later survey. The odds of reporting joint pain/stiffness often (odds ratio [OR] 7.26, 95% confidence interval [95% CI] 7.06-7.47) and taking antiinflammatory drugs (OR 4.44, 95% CI 2.37-8.33) were higher and physical functioning scores were lower (OR 3.75, 95% CI 3.56-3.95) when participants reported having OA. Variations in reporting OA coincided with episodic fluctuations in symptoms and functioning. Inconsistent reporting of OA could therefore reflect the presence of symptoms rather than reporting error and should be considered in longitudinal studies.


Review: Evolutionary link between prokaryotic and eukaryotic K+ channels.
Considering the importance of K+ channels in controlling the crucial K+ gradient across the plasma membranes of all living cells, it comes as no surprise that, besides being present in every eukaryotic cell, these integral membrane proteins have recently also been identified in prokaryotes. Today, approximately a dozen successfully completed and many more ongoing sequencing projects permit a search for genes related to K+ channels in the genomes of both eubacteria and archaea. The coding regions of homologues show a remarkable variety in primary structure. They predict membrane proteins with one, two, three and six hydrophobic segments surrounding a putative K+-selective pore (H5) and the presence or absence of a cytosolic putative NAD+-binding domain (PNBD) that probably senses the reducing power of the cell. The analysis of kinships on the basis of phylogenetic algorithms identifies sequences closely related to eukaryotic voltage-dependent Kv channels, but also defines members of a primordial class of prokaryotic K+ channel (containing the 2TMS/PNBD motif). Considering the unique mechanisms that may account for the assembly of modern proteins from different ancestral genes, and with more primary sequence data soon to appear, a scheme for the evolutionary origin of K+ channels comes within reach.


Extraction of DNA from soil using nanoparticles by magnetic bioseparation.
To develop a simple, rapid and inexpensive soil DNA extraction protocol. The protocol relies on the use of superparamagnetic silica-magnetite nanoparticles for the isolation and purification of DNA from soil samples. DNA suitable for use in molecular biology applications was obtained from a number of soil samples. The DNA extracted using the tested method successfully permitted the PCR amplification of a fragment of the bacterial 16S rDNA gene. The extracted DNA could also be restriction endonuclease digested. The protocol reported here is simple and permits rapid isolation of PCR-ready soil DNA. The method requires only small quantities of soil sample, is scalable and suitable for automation.


Infrared spectroscopic evidence supporting heterogeneous site binding models for humic substances.
Infrared spectroscopy was used to corroborate predictions made by newly developed heterogeneous site binding models for humic substances. Experimental conditions to acquire the spectra of soil humic substances (humic and fulvic acid and a polysaccharide fraction) in an aqueous state using horizontal attenuated total reflectance Fourier transform infrared spectroscopy (HATR-FTIR) were established. Elimination of the water spectrum from that of the sample was achieved by spectral subtraction of the water peak at 2020 cm(-1). A KSCN internal standard with an absorption band at 2067 cm(-1) was used to verify the efficacy of the subtraction procedure. Spectral artifacts produced by the water spectrum subtraction and from contaminants within the humic materials have been identified. Three fulvic and one humic acid solution were examined in solutions of varying pH. Results show that the observed proportion of ionized carboxylate in relation to pH is consistent with models that assume electrostatic effects and a continuous distribution of proton association constants (log KH). The spectroscopic data were in accordance with calculations made using the generic humic and fulvic acid NICA-Donnan model parameters.


The arterial pulse wave and vascular compliance.
For just over 1 century, we have relied on cuff sphygmomanometry to measure blood pressure at a peripheral (brachial) site. This measurement provides a quantitative snapshot of hemodynamic activity at 1 part of the arterial tree. Because the heart and brain are exposed to central (aortic) and not peripheral (brachial) pressure, it might be timely for nurses to start looking at alternative techniques to provide more meaningful information on central hemodynamics. The noninvasive technique of applanation tonometry allows such measurements to be performed quickly in the nursing clinic. By analyzing the pulse wave and calculating pulse wave velocity, the technique also assesses arterial "stiffness." This method of cardiovascular assessment further enables nurses to monitor the central effects of antihypertensive, lipid lowering, and other drug therapy over time.


[Diagnosis of the porphyrias : From A (as in aminolevulinic acid) to Z (as in zinc protoporphyrin)].
The porphyrias comprise a clinically, biochemically, and genetically heterogeneous group of predominantly hereditary metabolic disorders resulting from a dysfunction along the heme biosynthetic pathway. Whereas most variants can manifest with different cutaneous symptoms, some types only reveal life-threatening acute neurovisceral attacks. Therefore, interdisciplinary care of these patients is advisable. In this article, we provide an overview of characteristic clinical and laboratory findings in the various forms of porphyria and a diagnostic algorithm.


Automaker's fast-track process shows hospitals how to improve.
WHERE: Cleveland Clinic Foundation. Discharge of patients took up to eight hours. Satisfaction scores reflected patients' ire. Quality Choice Project for best discharge practices, plus a fast-track improvement process borrowed from General Motors.


The osteoblast-like differentiated phenotype of a variant of MG-63 osteosarcoma cell line correlated with altered adhesive properties.
A cell line, called MG-63.3A, was selected for its resistance to detachment from cell culture by a synthetic peptide containing the fibronectin cell-attachment sequence, Arg-Gly-Asp-Ser. The mechanism of this resistance is probably the 6-fold overproduction of the cell surface fibronectin receptor in MG-63.3A cells (Dedhar et al, J. Cell. Biol. 105, 1175-1182, (1987]. Compared to the parental, tumorigenic MG-63 cells, the non-tumorigenic MG-63.3A cells display strikingly different properties. These include an altered morphology, a slower proliferation rate, ability to form a calcified matrix in vitro, increased synthesis of type I collagen and expression of bone type alkaline phosphatase activity. Studies with purified growth factors indicate that the MG-63 and MG-63.3A cell lines respond to differentially to growth factors; the growth of MG-63 cells if stimulated by PDGF and GM-CSF and inhibited IL-1 beta, whereas the growth of MG-63.3A is unaffected by GM-CSF and IL-1 beta but is stimulated by PDGF and estradiol. We conclude from these data that the MG-63.3A cells may represent a more differentiated cell type with osteoblast-like properties. Studies are currently underway to further characterize, by electron microscopy, the calcified matrix formation by MG-63.3A cells.


[Conditionally pathogenic microorganisms in patients with bisphosphonate jaw osteonecrosis].
The objective of the study was to define treatment strategy in cases of facial bones bisphosphonate induced osteonecrosis based on the study of the role of conditionally pathogenic oral microorganisms. Three typical clinical cases of bisphosphonate osteonecrosis of the facial bones were analyzed and 15 conditionally pathogenic oral microorganisms were identified in these patients using real-time PCR in saliva, wound and bone samples. A comparative analysis was carried out with purulent-inflammatory diseases of maxillofacial area. The study results proved an important role of conditionally pathogenic microorganisms of the oral cavity in the development of osteonecrosis of the facial bones. Wide range of bacterial species was identified in osteonecrosis of the facial bones patients. While bone tissue is most exposed to microbial communities, surgical treatment results in effective rehabilitation for a long period.


Thyroidal radioisotope uptake in euthyroid cats: a comparison between 131I and 99mTcO4.
Two thyroidal evaluation systems in euthyroid cats (n = 12) were compared. A single, confirmed hyperthyroid cat was included for interest. Firstly, thyroidal uptake of an intravenous bolus of approximately 111 MBq (3 mCi) 99MTcO4 was estimated by using a scintillation camera and calculating the ratio of thyroid to salivary activities at 20 min and 4 h. Thyroid to salivary activity ratios were 1:1 at 20 min and 2:1 at 4 h. Two discrete areas of salivary uptake were identified, namely a parotid/mandibular complex and a more rostral buccal/sublingual complex. These results were compared to radioiodine uptake of an oral dose of approximately 0.925 MBq (25 microCi) 131I using a standard thyroid uptake system, measured at 1, 2, 4, 6, 8, 10, 12, 24 and 48 h after administration. Mean radioiodine thyroidal uptake started at 33% at 1 h, stabilised at 21% between 4 and 24 h, and dropped to 18% at 48 h. There was a significant correlation between the early thyroid:salivary ratio of the parotid/mandibular complex and the radioiodine uptake at 12 h.


Possible factors modifying the surgically induced astigmatism in cataract surgery.
To investigate possible modifiers of the surgically induced astigmatism with special reference to age, gender, preoperative astigmatism, and the intraocular pressure. Data for one hundred and one cataract patients operated on with extracapsular cataract extraction and intraocular lens implantation were prospectively recorded and followed for six years. Different explanatory variables like age, gender, preoperative astigmatism and postoperative intraocular pressure (IOP) were considered. Astigmatic changes were calculated as Naeser's polar values. The surgically induced astigmatism was not significant at one year, but was significantly increased 3- and 6-years postoperatively. At the same time the keratometric axis made a shift toward against-the-rule astigmatism. The postoperative mean-IOP was lower at all controls. Multiple regression analysis showed that a large preoperative astigmatism, a low postoperative IOP, and high age resulted in more surgically induced astigmatism against-the-rule. The length and the architecture of the incision are known to have an influence on the surgically induced astigmatism in cataract surgery. In the present study we used a multiple regression analysis model to show a significant correlation between the surgically induced astigmatism and age, preoperative astigmatism, and postoperative IOP.


Verruciform xanthoma in a bone marrow transplant recipient.
The verruciform xanthoma is an uncommon benign condition of uncertain cause that affects either mucosa or, less commonly, skin. Most lesions are solitary, and most have been reported to involve the oral mucosa. In some instances, chronic damage to the lesional site has been identified. This report describes a verruciform xanthoma that developed on the lower vermillion zone of the lip of a young person who had undergone allogeneic bone marrow transplantation for acute lymphoblastic leukemia. To our knowledge, this is the first reported case of this lesion occurring in a bone marrow transplantation patient. We speculate that immunologically mediated damage to the patient's epithelium in this area may be related to the pathogenesis of the lesion.


Comparative analysis of pelvic ligaments: a biomechanics study.
Pelvic organ prolapse (POP) affects one third of women of all ages and is a major concern for gynecological surgeons. In pelvic reconstructive surgery, native ligaments are widely used as a corrective support, while their biomechanical properties are unknown. We hypothesized differences in the strength of various pelvic ligaments and therefore, aimed to evaluate and compare their biomechanical properties. Samples from the left and right broad, round, and uterosacral ligaments from 13 fresh female cadavers without pelvic organ prolapse were collected. Uniaxial tension tests at a constant rate of deformation were performed and stress-strain curves were obtained. We observed a non-linear stress-strain relationship and a hyperelastic mechanical behavior of the tissues. The uterosacral ligaments were the most rigid whether at low or high deformation, while the round ligament was more rigid than the broad ligament. Pelvic ligaments differ in their biomechanical properties and there is fairly good evidence that the uterosacral ligaments play an important role in the maintenance of pelvic support from a biomechanical point of view.


Capillary isotachophoresis/NMR: extension to trace impurity analysis and improved instrumental coupling.
Building upon its promising initial performance, the online coupling of capillary isotachophoresis (cITP) to nuclear magnetic resonance (NMR) is extended to trace impurity analysis. By simultaneously concentrating and separating dilute charged species on the basis of their electrophoretic mobility, cITP greatly facilitates NMR structural elucidation. cITP/NMR appears particularly attractive for identifying trace charged synthetic and natural organic compounds obscured by large excesses of other components. A 9.4 microL injection of 200 microM (1.9 nmol) atenolol in a 1000-fold excess of sucrose (200 mM) is analyzed by cITP/NMR. A microcoil, the most mass sensitive NMR probe, serves as the detector as it provides optimal NMR observation of the capillary-scale separation. cITP successfully isolates the atenolol from the sucrose while concentrating it 200-fold to 40 mM before presentation to the 30 nL observe volume microcoil, thereby enabling rapid 1H NMR spectral acquisition of atenolol (experimental time of 10 s) without obstruction from sucrose. For this particular probe and sample, the stacking efficiency is near the theoretical limit as 67% of the sample occupies the 1 mm long microcoil during peak maximum. A multiple-coil probe with two serial 1 mm long microcoils arranged 1 cm apart has been developed to facilitate peak trapping and sample band positioning during cITP/NMR.


Prevalence of the factor VLeiden mutation among autopsy patients with pulmonary thromboembolic disease using an improved method for factor VLeiden detection.
Activated protein C resistance caused by factor VLeiden mutation is the most common inherited predisposing cause of venous thromboembolism, including pulmonary embolism (PE). We studied whether the incidence of factor VLeiden is higher among patients with PE evident at autopsy than in the general population. Paraffin-embedded fixed tissue blocks from all autopsy patients with diagnosed pulmonary thromboembolic disease during a 4-year period were collected for DNA extraction. Extraction and molecular analysis of the DNA was performed with an improved technique with an internal control to determine the presence of factor VLeiden mutation. Analysis of 82 autopsy cases with PE yielded 5 patients who were heterozygotes. Seventy-seven of the 82 patients analyzed were normal, and no homozygotes for factor VLeiden mutation were identified. This yielded a positive rate of 6% overall and 7% among white patients, which is similar to the incidence of heterozygotes in the white population. This study indicates that routine determination of factor VLeiden mutation is not warranted for patients with PE diagnosed at autopsy.


New supramolecular Au(I)-Cu(I) complex as potential luminescent label for proteins.
A novel supramolecular [Au6Cu2(C2C6H4-4-COONC4H4O2)6(Ph2PC6H4PPh2)3](PF6)2 complex functionalized with a succinimide ester alkynyl substituent has been synthesized and characterized using X-ray crystallography, mass spectrometry, and NMR spectroscopy. Like the other complexes of this class, it demonstrates bright emission in acetone and dichloromethane solutions with the excited state lifetime in a microsecond domain. This complex readily reacts with a surface amine group of proteins/enzymes (human serum albumin (HSA), rabbit anti-HSA antibodies, soybean trypsin inhibitor, and α-chymotrypsin) to give covalent conjugates, which contain up to five molecules of the luminescent label bound to the biomolecule. The conjugates keep a high level of the phosphorescent label emission, but in contrast to the parent complex molecule, display excellent solubility and high stability in physiological media. Investigation of the biological activity of the conjugates also showed that the specific structure of the biomolecules remained nearly unchanged upon bonding with the label, which is indicative of a very prospective of the conjugates application in biomolecular detection.


Cadmium-induced testes oxidative damage in rats can be influenced by dietary zinc intake.
We tested the hypothesis that zinc deficient animals would be characterized by an increased sensitivity to cadmium-induced oxidative damage to the testes. Weanling male rats were given free access to either a control (25 microg Zn/g) or a zinc deficient (0.5 microg Zn/g) diet; or restricted access to the 25 microg Zn/g diet at a level of intake similar to that of rats fed the 0.5 microg Zn/g diet. After 14 days on the diets, animals were injected s.c. with either saline or CdCl2 (2 mg Cd/kg body weight) solutions, and killed 24 h later. In the zinc-deficient group, testes weight and testes/body weight were higher in the cadmium-injected rats than in the saline-injected rats. The extent of hemorrhages, as indicated by high hemoglobin and testes iron concentrations was higher in the cadmium-treated zinc deficient group than in the cadmium-injected controls. In the zinc-deficient group, cadmium injection was associated with higher levels of lipid peroxidation (33% higher TBARS content) and protein oxidation (17% lower glutamine synthetase activity). Cadmium injection did not influence these parameters in the zinc-adequate groups. Extracellular superoxide dismutase activity was lower in the zinc-deficient group than in the zinc-sufficient groups; there was a trend (P < 0.06) for a lower activity in the cadmium- versus the saline-injected rats. These results support the concept that zinc deficiency increases the susceptibility of testes to cadmium-mediated free radical damage.


Evaluation of circulating tumor cells in patients with breast cancer: multi-institutional clinical trial in Japan.
With the development of the CellSearch System, it has become possible to measure circulating tumor cell (CTC) levels with high reproducibility, and the CTC test is currently being used clinically for patients with metastatic breast cancer in the United States. It is imperative that the clinical significance of the CTC test also be examined in Japan. Using the CellSearch System, CTC levels were evaluated in 57 healthy individuals and patients with benign breast disease; 30 patients with primary breast cancer (stages 1-3); and 38 patients with metastatic breast cancer. First, the relationship between CTC levels and the presence of metastasis was examined using a cutoff score of 2 CTCs per 7.5 ml whole blood. Then, the patients with metastatic breast cancer were divided into two groups, using a cutoff score of 5 CTCs per 7.5 ml blood, and progression-free survival (PFS) and overall survival (OS) were compared in the two groups. When the clinical cutoff score was set at 2 CTCs per 7.5 ml blood, 0% of the healthy individuals and patients with benign breast disease (0/57), 3.3% of the patients with primary breast cancer (1/30), and 50% of the patients with metastatic breast cancer (19/38) were identified as as having 2 CTCs per 7.5 ml blood. Additionally, with a cutoff score of 5 CTCs, 11 patients were reported to have 5 or more CTCs and both PFS (P = 0.0036) and OS (P = 0.04) were worse for this patient population than for the population with fewer than 5 CTCs. As concluded in a similar clinical trial in the United States, for patients with breast cancer, measuring CTC levels can be both an accurate indicator of metastases and an important measure of patient prognosis.


Demonstration of room-temperature laser action at 2.5 mum from Cr(2+):Cd(0.85)Mn(0.15)Te.
Room-temperature laser action from Cr(2+)-doped Cd(0.85)Mn(0.15)Te has been demonstrated for what is believed to be the first time. We achieved pulsed laser operation centered at ~2.5mu m by pumping into the mid-infrared absorption band of Cr(2+) ions by use of the 1.907- mum output of a H(2) Raman-shifted Nd:YAG laser. The output of the free-running Cr(2+):Cd(0.85)Mn(0.15)Te laser had a width of ~50 nm (FWHM), and the slope efficiency was calculated to be 5.5% under nonoptimum conditions.


The technique of synoviorthesis.
Synoviorthesis (medical synovectomy) is a commonly utilized procedure employed in the management of recurrent intra-articular bleeds and secondary chronic synovitis in haemophilic patients. The procedure involves the intra-articular administration of an agent in order to induce fibrosis in the inflamed synovium so reducing the bleeding tendency. Such agents may either be chemical based (osmic acid, rifampicin) or radioactive (yttrium, gold or phosphorus). Whichever agent is employed care must be taken to avoid extra-articular complications (radiation burn and/or inflammatory reaction) as a result of extravasation or needle track contamination. The most frequently affected joints in haemophilia are the elbows, knees and the ankles, and to a lesser extent the shoulders and hips. This article outlines the techniques of injection of the five aforementioned joints, with details of the anatomical landmarks to perform the injections correctly. Injection of the elbows, knees and ankles may be carried out simply on an out-patient basis under local anaesthesia. However, it is advisable to perform injection of the shoulder or hip under radiographic control in order to ensure accurate placement. Very young children may require either sedation or a general anaesthetic. Strict asepsis is naturally a paramount requirement.


Efficacy and safety analysis according to histology for S-1 in combination with carboplatin as first-line chemotherapy in patients with advanced non-small-cell lung cancer: updated results of the West Japan Oncology Group LETS study.
A phase III study (Lung Cancer Evaluation of TS-1) previously demonstrated noninferiority in terms of overall survival (OS) at interim analysis for carboplatin-S-1 compared with carboplatin-paclitaxel for first-line treatment of advanced non-small-cell lung cancer (NSCLC). A total of 564 patients were randomly assigned to receive either carboplatin on day 1 plus oral S-1 on days 1-14 or carboplatin-paclitaxel on day 1 every 21 days. Updated results and post hoc subgroup analysis according to tumor histology are presented. The updated analysis revealed a median OS of 15.2 months in the carboplatin-S-1 arm and 13.1 months in the carboplatin-paclitaxel arm, with a hazard ratio (HR) of 0.956 [95% confidence interval (CI) 0.793-1.151], consistent with the previous primary analysis. Median OS was 14.0 months in the carboplatin-S-1 arm and 10.6 months in the carboplatin-paclitaxel arm (HR 0.713; 95% CI 0.476-1.068) for patients with squamous cell carcinoma (SCC), with corresponding values of 15.5 and 13.9 months (HR 1.060; 95% CI 0.859-1.308) for those with non-SCC. These results establish the efficacy and safety of carboplatin-S-1 in patients with advanced NSCLC regardless of tumor histology.


Postconcussion syndrome in athletes.
Postconcussion syndrome (PCS) is a constellation of physical, cognitive, and emotional symptoms that persist in a small percentage of patients who suffer from a concussion. There is significant debate regarding the definition and pathophysiology of PCS. This article reviews these controversies, the factors that may predict PCS, potential diagnostic and treatment options, and return-to-activity considerations for the sports medicine physician.


The measuring of blood pressure during pregnancy.
This is an evaluation of the methodology of blood pressure measurement in a high-risk obstetric clinic. Blood pressure values were obtained from 149 patients by the clinic staff and the research project coordinator. The project coordinator using the random-zero sphygmomanometer measured lower systolic and higher diastolic values. The diastolic and systolic values increased after 30 weeks of pregnancy up to term. Agreement among observers is low for diastolic blood pressure. The clinic staff measured about 50% of the values with a zero terminal digit as compared with only 14% by the project coordinator. The fourth Korotkoff sound can be recorded in 83% of the patients. The mean diastolic blood pressures obtained with the fourth sound are significantly higher than when the fifth sound is used. Recommendations are offered for blood pressure measuring during pregnancy, and it is strongly suggested that the same methodologic rigor be used as in any other medical procedure.


Suicide and the reluctance of young men to use mental health services.
Young men are grossly over represented in Irish suicide statistics, yet this group is the least likely to use mental health services. This paper outlines why young men are reluctant to access mental health services, framing the problem in the context of risk factors for suicide such as binge drinking and social change. The paper argues that de-stigmatising mental illness and encouraging young men to seek help for emotional problems should be a priority for policymakers.


Depot-specific and hypercaloric diet-induced effects on the osteoblast and adipocyte differentiation potential of adipose-derived stromal cells.
Adipose-derived stromal cells (ADSCs) can be differentiated in vitro into several mesenchyme-derived cell types. We had previously described depot-specific differences in the adipocyte differentiation of ADSCs, and consequently we hypothesized that there may also be depot-specific differences in osteoblast differentiation of ADSCs. For this study, the osteoblast differentiation potential of rat subcutaneous ADSCs (scADSCs) and perirenal visceral ADSCs (pvADSCs) was compared. Osteoblast differentiation media (OM) induced markers of the osteoblastic phenotype in scADSCs, but not in pvADSCs. ADSCs harvested from rats with diet-induced visceral obesity (DIO) exhibited reduced osteoinduction, compared to lean controls, but adipocyte differentiation was not affected. Expression of the pro-osteogenic transcription factor Msx2 was significantly higher in naïve scADSCs from lean and DIO rats than in pvADSCs. Our findings indicate that ADSCs from different anatomical sites are uniquely pre-programmed in vivo in a depot-specific manner, and that diet-induced metabolic disturbances translate into reduced osteoblast differentiation of ADSCs.


Tarsal Coalition in Pediatric Patients.
A fibrous, cartilaginous, or bony (or a combination thereof) connection between two tarsal bones, or tarsal coalition usually involves the calcaneonavicular or talocalcaneal articulations. Foot pain, beginning when an initially fibrous coalition becomes partially or totally osseous and coinciding with trauma or increased stress such as athletic activity, is the usual presenting symptom. Although often identified on radiographs of the foot (including specialized projections), tarsal coalitions are increasingly imaged with computed tomography of the feet. Plain tomography, single contrast arthrography, and bone scintigraphy are no longer used in the evaluation of tarsal coalition. Magnetic resonance imaging has some advantages over computed tomography but its exact role remains undetermined. Surgical resection of symptomatic tarsal coalitions is used when conservative methods fail to alleviate symptoms.


A novel derivatization approach for determination of ketamine in urine and plasma by gas chromatography-mass spectrometry.
A new method was developed for determination of ketamine (KT) in urine and plasma samples by derivatization and gas chromatography-mass spectrometry. In this article, KT was first derivatized with sodium nitrite to volatile N-nitrosamines under acidic condition. Then the derivative had been identified by the mass spectra. The derivatization conditions including the amount of hydrochloric acid, the amount of sodium nitrite, reaction temperature, reaction time and the extraction reagents were optimized. Calibration curves were linear in the range of 0.04-20 μg mL(-1) for KT, and the limit of detection (LOD) and limit of quantitation (LOQ) were 0.01 μg mL(-1) and 0.04 μg mL(-1), respectively. The results of recovery indicated that the method had good precision and reproducibility. Compared with existing derivatization methods, this method provided a rapid, convenient, effective and low-cost way for gas chromatography method of KT quantification.


Danazol: objective assessment in the treatment of endometriosis.
The objective assessment of Danocrine (Danazol, Winthrop) in the treatment of endometriosis was hampered in the 1970s by the absence of a universally accepted classification. The American Fertility Society (AFS) classification, proposed in 1979, has now become widely accepted. However, there is a lack of recorded objective data utilizing the AFS score before and after Danazol therapy. In a series of 51 patients with endometriosis, who underwent laparoscopy, then received Danazol, 800 mg daily for 6 months, and had a repeat laparoscopy, there was a statistically significant improvement in the AFS score in Stage I and II disease.


[Clinical ethology: a study of stereotypies].
According to ethological procedures and concepts, the author tries to describe the shape and the functional value of stereotyped movements in disabled children. These pathological behaviors are not a fixed response, they take place within an intricate behavioral sequence which associates many items; they are one aspect of a pathological answer to social stimulation. They prove the disabled child's intense motivation to communicate, but show the impossibility for him to do so. The inability to generate an adapted behavioral sequence shows that the deficit concerns an essential interaction process.


The 'Disadapted' Animal: Niko Tinbergen on Human Nature and the Human Predicament.
This paper explores ethologist Niko Tinbergen's path from animal to human studies in the 1960s and 1970s and his views about human nature. It argues, first, that the confluence of several factors explains why Tinbergen decided to cross the animal/human divide in the mid 1960s: his concern about what he called "the human predicament," his relations with British child psychiatrist John Bowlby, the success of ethological explanations of human behavior, and his professional and personal situation. It also argues that Tinbergen transferred his general adaptationist view of animal behavior to the realm of human biology; here, his concern about disadaptation led him to a view of human behavior that was strongly determined by the species' evolutionary past, a position that I call evolutionary determinism. These ideas can be seen in the work he carried out with his wife, Elisabeth Tinbergen, on autism. The paper concludes that Tinbergen's vision of human nature constitutes another version of what anthropologist Clifford Geertz called in 1966 the "stratigraphic" conception of the human: a view of human nature as a composite of levels in which a universal ancestral biological core is superimposed by psychological and cultural layers that represent accidental variation at best and pathological deviation at worst.


[Surgical therapy in cholecysto-/choledocholithiasis. Results of a Germany-wide questionnaire sent to 859 clinics with 123,090 cases of cholecystectomy].
With the advent of laparoscopic cholecystectomy, the choice of procedure (laparoscopic vs open) and surgical management in gallstone disease are of interest. The purpose of this study was to examine the current approach and various strategies for cholecystectomy in Germany. A retrospective survey at 859 (of 1,200, 67.6%) hospitals in Germany was conducted. Data from 123,090 patients that had undergone cholecystectomy were analyzed. 71.9% of the procedures were finished laparoscopically (LC: 88.537), whereas 22.5% (27.727) were done in the open technique (KC). Conversion to open surgery was required in 7.1% of the laparoscopically started operations, mainly in cases of adhesions and unclear anatomic situations (64.3%). When common bile duct (CBD) stones were diagnosed preoperatively, 74.4% of the participants favored primary endoscopic extraction (ERC), followed by LC. In cases of intraoperative diagnoses, the LC was finished and postoperative ERC and extraction were carried out in more than half of the hospitals (58.4%). Sixteen percent were converted to an open operation with simultaneous exploration of the CBD. Laparoscopic desobstruction of the CBD was extremely rare (4.4%). The intraoperative cholangiography (IOC) was the most strongly recommended approach for intraoperative diagnostics, but was generally routine practice in only 6% of the hospitals conducting LCs. Forty-nine percent of the respondents reported the use of IOC in selected cases and 43% of the hospitals did not perform any intraoperative diagnostics in LC. Compared with OC, the results show a lower incidence of postoperative reinterventions (0.9 vs 1.8%) and fatal outcomes (0.04 vs 0.53%) for LC. In contrast, CBD injuries were more frequent in the LC group (0.32 vs 0.12%). The median duration of hospitalization was 6.1 days (range 2.8-12) in the LC group compared with 10.4 days (range 3-28) in the OC group. LC is the standard procedure for the treatment of uncomplicated gallstone disease. Even after adjustment for differences in patient comorbidities, there are logical differences between the hospitals as to the type of cholecystectomy used for acute cholecystitis, the management of CBD stones, and the intraoperative diagnostics in LC.


[Lung cancer in elderly patients].
Lung cancer occurring in elderly patients is an increasingly frequent clinical problem both because of an aging population and the general increase in incidence of the disease. The management of lung cancer in the elderly represents therefore a significant public health problem. The full range of therapeutic modalities may be used in these patients provided a comprehensive geriatric assessment is made, not limited to performance status assessment, but also taking into account comorbidities, which are frequent in elderly people, and functional capacities. Elderly patients are often managed in a sub-optimal fashion. With appropriate, equal treatment their prognosis is equivalent to that of younger patients.


New species of Heteropterna Skuse and Keroplatus Bosc (Diptera: Keroplatidae) become the second records of this family for Cuba.
Two new species of Keroplatini (Diptera: Keroplatidae: Keroplatinae), Heteropterna (Heteropterna) garae n. sp. and Keroplatus maxi n. sp. are described from Cuba, the second record of the family from this territory since Matile's paper in 1977. Heteropterna garae n. sp. is characterized by the last three flagellomeres being a silvery white colour (the last with a light brown apical border), the wings with a distinct colour pattern, and the unique shape of the terminalia and gonostylus. Keroplatus maxi n. sp. is principally yellow with almost no marks except for the particular pattern of stripes on the dorsal part of thorax. The wings have a slight pale yellowish tint with no pattern of coloured spots, and the gonostylus is characteristically shaped. A key to Neotropical Heteropterna and Keroplatus species is provided.


Pharmacologic studies of continuous infusion of arabinosylcytosine by liquid infusion system.
Arabinosylcytosine (ara-C) was administered by prolonged intravenous infusion with a portable liquid infusion system (LIS) to patients with acute myelogenous leukemia. With the use of tritiated ara-C and this portable system, pharmacologic studies were performed in 8 patients. Most of the plasma radioactivity is in the deaminated product, arabinosyluracil (ara-U). After continuous intravenous infusion, a constant ara-C level is achieved slowly in the plasma. Unless a loading (priming) dose is administered immediately before beginning the infusion, a steady-state ara-C level cannot be achieved until 8 to 24 hr after the infusion. The infusion system has two mechanisms--one for giving a loading dose (3 ml/min) and the other for regular infusion at a rate of 0.5 to 2.0 ml/hr. If a loading dose is given before continuous infusion, a steady-state are-C level is achieved within an hour. The plasma ara-C disappearance curves are biphasic with a terminal half-life of 104 min, which is the same as that of a single injection. The cumulative urinary excretion after approximately 23 hr of infusion varied from 14% to 35% in different patients; more than 90% is ara-U and the remainder is ara-C. Our results have demonstrated that LIS can be used conveniently to sustain a constant plasma level of ara-C. The LIS increases mobility of both inpatients and outpatients and is particularly convenient for ambulatory patients.


Selective stimulation of tissue-type plasminogen activator (t-PA) in vivo by infusion of bradykinin.
Angiotensin converting inhibitors (ACEI) not only decrease angiotensin II (Ang II) but also potentiate the effects of bradykinin. Bradykinin is a potent stimulus to tissue type plasminogen activator (t-PA) secretion in animal models. In this study, we tested the hypothesis that bradykinin increase t-PA levels in humans. Bradykinin was infused in seventeen hypertensive patients randomized to treatment with the ACEIs captopril and quinapril or with placebo. Bradykinin caused a significant decrease in mean arterial pressure (MAP) (p = 0.014) and increase in pulse (p < 0.001). ACEI significantly potentiated the hemodynamic effect of bradykinin (p < 0.05). Although baseline t-PA antigen levels were similar in the ACEI-treated (6.85 +/- 0.85 ng/ml) and placebo-treated (7.85 +/- 0.68 ng/ml) subjects, bradykinin caused a significant (p < 0.01) increase in t-PA antigen levels (to 19.3 +/- 8.2) only in the ACEI-treated patients. This increase in t-PA was independent of activation of the sympathetic nervous system. Bradykinin had no effect on PAI-1 antigen levels. These in vivo data suggest that infusion of bradykinin results in an increase in circulating t-PA levels without an effect on PAI-1.


Subwavelength fractional Talbot effect in layered heterostructures of composite metamaterials.
We demonstrate that under certain conditions, fractional Talbot revivals can occur in heterostructures of composite metamaterials, such as multilayer positive- and negative-index media, metallodielectric stacks, and one-dimensional dielectric photonic crystals. Without recourse to the paraxial approximation, we also obtain Talbot images for the feature sizes of transverse patterns smaller than the illumination wavelength. A general expression for the Talbot distance in such structures is derived, and the conditions favorable for observing Talbot effects in layered heterostructures are discussed.


Cloning and expression of codon-optimized recombinant darbepoetin alfa in Leishmania tarentolae T7-TR.
Darbepoetin alfa is an engineered and hyperglycosylated analog of recombinant human erythropoietin (EPO) which is used as a drug in treating anemia in patients with chronic kidney failure and cancer. This study desribes the secretory expression of a codon-optimized recombinant form of darbepoetin alfa in Leishmania tarentolae T7-TR. Synthetic codon-optimized gene was amplified by PCR and cloned into the pLEXSY-I-blecherry3 vector. The resultant expression vector, pLEXSYDarbo, was purified, digested, and electroporated into the L. tarentolae. Expression of recombinant darbepoetin alfa was evaluated by ELISA, reverse-transcription PCR (RT-PCR), Western blotting, and biological activity. After codon optimization, codon adaptation index (CAI) of the gene raised from 0.50 to 0.99 and its GC% content changed from 56% to 58%. Expression analysis confirmed the presence of a protein band at 40 kDa. Furthermore, reticulocyte experiment results revealed that the activity of expressed darbepoetin alfa was similar to that of its equivalent expressed in Chinese hamster ovary (CHO) cells. These data suggested that the codon optimization and expression in L. tarentolae host provided an efficient approach for high level expression of darbepoetin alfa.


Biotherapy in Inflammatory Diseases of the CNS: Current Knowledge and Applications.
Biotherapy represents an innovative therapeutic approach that includes immunotherapy (vaccines, apheresis, and antibodies); gene therapy; and stem cell transplants. Their development helps to cross the bridge from bench to bedside and brings new hope of a cure for severe diseases in different fields of medicine. In neurology, a growing range of applications is being developed for these medications. Valuable results are now available in the field of autoimmunity, neuro-oncology, paraneoplastic manifestations, and neurodegenerative disorders. In this review, we examine the current and future applications of biotherapy in the field of inflammation of the central nervous system. We demonstrate its contribution in clinical practice, where it has enabled a significant level of effectiveness to be achieved. Indeed, the efficacy of these new biodrugs provides a solution for patients refractory to standard therapies, such as intravenous immunoglobulins in limbic encephalitis, plasma exchanges in neuromyelitis optica and anti-CD20 monoclonal antibodies in multiple sclerosis. They also mark the first steps towards individualized medicine.


The repetition decrement effect in recognition memory: The influence of prime-target spacing.
Rosner, Lopez-Benitez, D'Angelo, Thomson, and Milliken (2018, see also Collins, Rosner & Milliken, 2018) reported a novel recognition memory effect. In an incidental study phase, participants saw prime-target word pairs and were asked to name aloud just the target. Primes were unmasked, but participants were not required to attend to them. On repeated trials the prime and target were the same word, whereas on not-repeated trials the prime and target were different words. In the following test phase, recognition memory was better for not-repeated targets than for repeated targets. The present study explores whether this effect is influenced by the spacing between primes and targets. The results replicated prior studies in that immediate repetition resulted in a repetition decrement effect, but spaced repetition (by about 10 min) resulted in the opposite effect - better recognition for repeated than not-repeated targets. The results are discussed in relation to deficient processing theories of the spacing effect.


Anatomy and potential clinical significance of the vastoadductor membrane.
Few reports are found in the extant medical literature regarding the vastoadductor membrane. This membrane effectively creates a subcompartment within the subsartorial canal. The lower limbs of 16 embalmed adult cadavers were dissected to identify the vastoadductor membrane and note its measurements. A vastoadductor membrane was identified in all specimens and was derived from the medial intermuscular septum. This membrane connected the medial edge of the vastus medialis muscle to the lateral edge of the adductor magnus muscle. Membranes were all wider proximally and narrowed distally. The mean length of this structure was 7.6 cm. The mean width of the vastoadductor membrane at its proximal, midportion, and distal parts was 2.2, 1.7, and 0.5 cm, respectively. The mean distance from the anterior superior iliac spine to the proximal border of the vastoadductor membrane was 28 cm. The mean distance from the distal border of the membrane to the adductor tubercle was 10 cm. Seventy-five percent of specimens exhibited a fenestrated vastoadductor membrane. Branches of the saphenous nerve to the skin of the medial thigh pierced the vastoadductor membrane in 31% of specimens. Two specimens demonstrated branches derived from the branch of the obturator nerve that pierced this membrane en route to the skin of the medial thigh. Perforating venous branches from the great saphenous vein were identified in 22% of specimens. As compression of the femoral artery at the adductor hiatus is a well-recognized entity, the clinician may also try to explore potential compression of this vessel more proximally by an overlying vastoadductor membrane. The authors would also hypothesize that due to the interconnection between the adductor magnus and vastus medialis by the vastoadductor membrane that a potential synergy exists between the functions of these two muscles.


Neuronal pp60c-src contains a six-amino acid insertion relative to its non-neuronal counterpart.
Neuronal cells express a pp60c-src variant that displays an altered electrophoretic mobility and a different V8 peptide pattern relative to pp60c-src expressed in tissues of non-neuronal origin. To determine whether the neuronal form of pp60c-src is encoded by a brain-specific messenger RNA, a mouse brain complementary DNA (cDNA) library was screened with a chicken c-src probe and a 3.8-kilobase c-src cDNA clone was isolated. This clone encodes a 60-kilodalton protein that differs from chicken or human pp60c-src primarily in having six extra amino acids (Arg-Lys-Val-Asp-Val-Arg) within the NH2-terminal 16 kilodaltons of the molecule. S1 nuclease protection analysis confirmed that brain c-src RNA contains an 18-nucleotide insertion at the position of the extra six amino acids. This insertion occurs at a position that corresponds to a splice junction in the chicken and human c-src genes. The isolated c-src cDNA clone encodes a protein that displays an identical V8 peptide pattern to that observed in pp60c-src isolated from tissues of neuronal origin.


Identification of Amyloidogenic Regions in the Spine of Insulin Fibrils.
To reveal conformational changes resulting in the formation of insulin fibrils, it is necessary to identify amyloidogenic regions in the structure of protein monomers. Different models of insulin fibrillogenesis have been proposed previously. However, precise regions responsible for the formation of amyloid fibrils have not been identified. Using bioinformatics programs for predicting amyloidogenic regions, we have determined some common amyloidogenic sequences in the structure of insulin monomers. The use of limited proteolysis and mass spectrometry analysis of the obtained protein fragments resistant to the action of proteases allowed us to identify amino acid sequences in the insulin structure that can form the spine of the insulin fibrils. The obtained results are in agreement with the earlier proposed model of fibril formation from the ring-like oligomers and can be used for designing insulin analogs resistant to amyloidogenesis.