[Sensory input and basal ganglia].
Non-motor symptoms including sensory signs have recently been stressed in basal ganglia (BG) disorders. Why do sensory symptoms appear in BG disorders? Four closed loops have been shown between cortex and BG, but no sensory cortical-BG loops. I review two points: fiber connections between the somatosensory cortex and BG to explain sensory symptoms, and pain and basal ganglia. Somatosensory system and BG Many animal studies have shown somatosensory cortex- striatum- globus pallidus- motor thalamus connections, but no connections to the sensory thalamus. This indicates that sensory system may modulate four closed loops between the cortices and BG (motor loop, oculomotor loop, prefrontal loop and limbic loop) as an open loop system. Based on the above findings, two possible mechanisms may explain somatosensory symptoms in BG disorders. Motor modulation abnormalities may be considered as sensory symptoms in patients with BG disorders. Some sensory cognition abnormalities due to abnormal modulation of the prefrontal- BG loop may be considered as sensory symptoms. Pain and dopamine Two systems contribute to pain signs in patients with BG disorders. Descending pain modulation system: several brainstem nuclei send descending pain modulation fibers to the spinal cord mediated by serotonin or noradrenalin. These nuclei are facilitated by D2 neurons from the striatum. Striatal dopamine must suppress the pain information input at the spinal cord. Ascending pain relief system D2 neurons from the ventral tegmental area to anterior cingulate cortex, accumbens and amygdala may reduce pain feeling at the association cortices. In summary, dopamine system will reduce pain at the spinal cord and association cortices. Dopamine depletion, therefore, will enhance the pain sensation.


Combination of granulocyte colony-stimulating factor and low-dose cytosine arabinoside further enhances myeloid differentiation in leukemia cells in vitro.
We examined the differentiation-inducing effect on freshly isolated myeloid leukemia cells in liquid suspension culture by combined treatment with granulocyte colony-stimulating factor (G-CSF) plus low-dose cytosine arabinoside (Ara-C; 5-10 ng/ml) in 25 patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) in leukemic transformation. Culture with G-CSF alone showed leukemic cell growth stimulation in 15 out of the 25 cases (60%) and induction of cell differentiation in 19 out of the 25 cases (76%), respectively. In 23 cases (92%), either growth stimulation and/or differentiation induction of leukemia cells was observed in response to G-CSF. This suggests that most myeloid leukemia cells are able to respond to G-CSF stimulation. In addition, treatment of cells with low-dose Ara-C alone resulted in the enhancement of myeloid specific antigens expression in 16 cases (64%). Treatment of leukemia cells with higher concentrations of Ara-C (over 50 ng/ml) alone resulted in cytocidal effects but not in the induction of differentiation. Furthermore, 15 cases (60%) showed pronounced myeloid differentiation of leukemia cells after combined exposure to G-CSF plus low-dose Ara-C as compared with cells treated with either G-CSF or Ara-C alone. The enhanced effect of differentiation induction by combining G-CSF plus low-dose Ara-C was also observed in a murine myeloid leukemia cell line WEHI-3B in vitro. These data suggest that treatment with G-CSF plus low-dose Ara-C is capable of inducing differentiation of leukemic cells in vitro, and also appears to be useful for the differentiation-based therapy of patients with AML and MDS.


Metformin for Treatment of Overweight Induced by Atypical Antipsychotic Medication in Young People With Autism Spectrum Disorder: A Randomized Clinical Trial.
Atypical antipsychotic medications are indicated for the treatment of irritability and agitation symptoms in children with autism spectrum disorder (ASD). Unfortunately, these medications are associated with weight gain and metabolic complications that are especially troubling in children and with long-term use. To evaluate the efficacy of metformin for weight gain associated with atypical antipsychotic medications in children and adolescents with ASD (defined in the protocol as DSM-IV diagnosis of autistic disorder, Asperger disorder, or pervasive developmental disorder not otherwise specified), aged 6 to 17 years. A 16-week, double-blind, placebo-controlled, randomized clinical trial was conducted at 4 centers in Toronto, Ontario, Canada; Columbus, Ohio; Pittsburgh, Pennsylvania; and Nashville, Tennessee. In all, 209 potential participants were screened by telephone, 69 individuals provided consent, and 61 participants were randomized to receive metformin or placebo between April 26, 2013, and June 24, 2015. Metformin or matching placebo titrated up to 500 mg twice daily for children aged 6 to 9 years and 850 mg twice daily for those 10 to 17 years. The primary outcome measure was change in body mass index (BMI) z score during 16 weeks of treatment. Secondary outcomes included changes in additional body composition and metabolic variables. Safety, tolerability, and efficacy analyses all used a modified intent-to-treat sample comprising all participants who received at least 1 dose of medication. Of the 61 randomized participants, 60 participants initiated treatment (45 [75%] male; mean [SD] age, 12.8 [2.7] years). Metformin reduced BMI z scores from baseline to week 16 significantly more than placebo (difference in 16-week change scores vs placebo, -0.10 [95% CI, -0.16 to -0.04]; P = .003). Statistically significant improvements were also noted in secondary body composition measures (raw BMI, -0.95 [95% CI, -1.46 to -0.45] and raw weight, -2.73 [95% CI, -4.04 to -1.43]) but not in metabolic variables. Overall, metformin was well tolerated. Five participants in the metformin group discontinued treatment owing to adverse events (agitation, 4; sedation, 1). Participants receiving metformin vs placebo experienced gastrointestinal adverse events during a significantly higher percentage of treatment days (25.1% vs 6.8%; P = .005). Metformin may be effective in decreasing weight gain associated with atypical antipsychotic use and is well tolerated by children and adolescents with ASD. clinicaltrials.gov Identifier: NCT01825798.


Factors associated with the incidence of urban visceral leishmaniasis: an ecological study in Teresina, Piauí State, Brazil.
The objective of this study was to identify socioeconomic and environmental factors associated with the incidence of visceral leishmaniasis in the city of Teresina, Piauí State, Brazil. This was an ecological study based on 1,744 cases reported from 1991 to 2000, and the city's neighborhoods served as the unit of analysis. Mean annual incidence rates were related to socioeconomic and demographic indicators and a vegetation index derived from remote sensing images by means of spatial multiple linear regression models. The neighborhoods with the highest incidence rates were mostly located in the city's peripheral areas. Multivariate analysis identified an interaction between population growth and the vegetation index, so that areas with high population growth and abundant vegetation showed the highest incidence rates. The percentage of households with piped water was inversely associated with visceral leishmaniasis incidence. Spatial distribution of visceral leishmaniasis in Teresina during the 1990s was heterogeneous, and incidence of the disease was associated with the peripheral neighborhoods with the heaviest vegetation cover, subject to rapid occupation and lack of adequate sanitation infrastructure.


Antigenotoxic and antioxidant potential of aqueous fraction of ethanol extract of Mentha spicata (L.) against 4-nitroquinoline-1-oxide-induced chromosome damage in mice.
The antigenotoxic potential of an aqueous fraction of ethanol extract of Mentha spicata was evaluated by measuring the frequency of micronucleated polychromatic erythrocytes (MnPCEs) in mice bone marrow, using 4-nitroquinoline-1oxide (NQO) as the reference mutagen. In addition, lipid peroxidation (LPO) and antioxidant levels were also quantified with liver tissue of the same mice to assess their antioxidant potential. Swiss albino mice of either sex (25-30 g) were orally pretreated with an aqueous fraction (80, 160, and 320 mg/kg) for 5 consecutive days. NQO (7.5 mg/kg) was injected intraperitoneally after 2 hours until the final day (day 5) of treatment with aqueous fraction. Animals were sacrificed 24 hours later by cervical dislocation and processed for micronuclei and bioassays. A significant reduction (about 67%) of NQO-induced MnPCE frequency was observed at the dose of 320 mg/kg. The LPO was also suppressed effectively, with concomitant changes in both enzymatic and nonenzymatic antioxidants. The restoration level was dose dependent in LPO and glutathione-s-transferase, whereas it was dose independent in superoxide dismutase, glutathione peroxidase, catalase, and reduced glutathione. The results indicate that the aqueous fraction of M. spicata mediates their antigenotoxic effects by the modulation of LPO and antioxidant enzymes.


Neuro-Behçet's syndrome: differential diagnosis and management.
Behçet's syndrome (BS) is a multisystem disease of unknown etiology, characterized by chronic relapsing cardinal symptoms of orogenital ulcers, uveitis, and different skin lesions. Its major pathologic feature is vasculitis. Neuro-Behçet's syndrome (NBS) is defined as a constellation of neurologic manifestations with characteristic neuropathologic findings, usually confirmed by ancillary investigations, in patients who meet the diagnostic criteria for BS. Neurologic manifestations of the syndrome are more common in male patients and have been reported to occur in anywhere from 5% to 50% of BS patients, depending on their geographical region. NBS primarily affects the central nervous system and includes parenchymal and nonparenchymal involvement. Peripheral neuropathy and myopathy are rare. Immunosuppression is widely used for treatment.


[The effect of substances with nootropic activity on oxidative phosphorylation in brain mitochondria in acute craniocerebral trauma].
An open craniocerebral trauma was simulated in rat experiments. Oxidative phosphorylation in the brain mitochondria was studied by polygraphy 24 h after the trauma. It was found that trauma to the brain leads to inhibition of respiration in mitochondria in various metabolic states. Nooglutil in a dose of 50 mg/kg prevents these changes. Nooglutil is more effective than picamilon (500 mg/kg) and piriditol (100 mg/kg).


Clinical trial methods to discover and validate predictive markers for treatment response in cancer.
Although postoperative chemotherapy in the treatment of cancer appears to have reached the limit of cytoreduction, this may be due to chemotherapeutic agents that are administered nonselectively rather than attainment of the true limit of cytoreduction. Molecular profiles of tumor cells may determine tumor response to chemotherapy, and therefore the selective use of chemotherapy based on prediction will ultimately provide a cure for breast cancer. In this paper, design strategies for clinical trials aimed at disclosing predictive markers are discussed.


Endocrinology and suicide.
The data accumulated so far suggest several tentative conclusions. First, thyroid and adrenal gland disease unquestionably can produce severe mental disturbances. Most of these are "organic" in nature, but depressive symptoms are common as well. A connection between these diseases and suicide has not been established, however. Research cannot really address this possibility adequately, since these studies are difficult, if not impossible, to do in the postmortem state at this time. Ways should continue to be sought to overcome this problem. Clinically, it seems advisable to treat all depressed, suicidal persons with the same caution, whether they have diseases of these endocrine systems or not. The differences in responsiveness of the thyroid and adrenocortical systems among depressed and perhaps truly suicidal persons are of greater theoretical as well as practical clinical interest. The TRH-TSH test and the DST may not be as specific as once thought. Nonetheless, the abnormalities do occur with regularity in specific subgroups of depressed patients. It is far too early to stop research on the DST or the TRH-TSH test. Clinically, however, it is premature to make important management decisions about suicidal patients based on these test results. At this time, we really have no means of pinpointing the persons who will eventually suicide. The hope that they may someday provide valid data for assessing real suicide potential is there, and clinicians should stay informed in this arena. Until that day comes, though, we must continue to exercise caution regarding our clinical judgments and to live with their uncertainties.


[Research on rice blast, corn and broad bean rust leaves by FTIR spectroscopy].
Fourier transform infrared Spectroscopy (FTIR) was used to study healthy and diseased leaves of rice, corn, and broad bean. The results show that the infrared spectra of the leaves are mainly composed of the absorption bands of proteins and polysaccharide. The spectra are similar, but the differences were observed in the peak positions, shapes, and absorption ratios. The remarkable differences in correlation coefficients were also observed in the region of 1 800-1 000 cm(-1) of the second derivate spectra. The absorption ratio A1 056 /A1 652 of healthy rice leaves and rice blast leaves, A1 652/A2 920 of healthy broad bean leaves and leaves, A1 056/A2 920 of healthy corn and corn rust (non-lesion site), and A1 652/A2 920 of healthy corn and corn rust (lesion site) all show a decline from healthy to diseased leaves, showing that the contents of polysaccharide and the protein have some differences.


Near-infrared laser desorption/ionization aerosol mass spectrometry for investigating primary and secondary organic aerosols under low loading conditions.
A new method, near-infrared laser desorption/ionization aerosol mass spectrometry (NIR-LDI-AMS), is described for the real time analysis of organic aerosols at atmospherically relevant mass loadings. Use of a single NIR laser pulse to vaporize and ionize particle components deposited on an aluminum probe results in minimal fragmentation to produce exclusively intact pseudomolecular anions at [M-H](-). Limits of detection (total particulate mass sampled) for oxidized compounds of relevance to atmospheric primary and secondary organic aerosol range from 89 fg for pinic acid to 8.8 pg for cholesterol. NIR-LDI-AMS was used in conjunction with the University of Vermont Environmental Chamber to study secondary organic aerosol (SOA) formation from ozonolysis of limonene at total aerosol mass loadings ranging from 3.2 to 25.0 μg m(-3) and with a time resolution of several minutes. NIR-LDI-AMS permitted direct delineation between gas-phase, homogeneous SOA formation and subsequent heterogeneous aerosol processing by ozone.


Four new bibenzyl derivatives from Dendrobium candidum.
Four new bibenzyl derivatives, namely, dendrocandins F-I (1-4), were isolated from the stems of Dendrobium candidum. Their structures were elucidated by the analysis of spectroscopic data. Dendrocandins F and G represent the fourth and fifth example of bisbibenzyl derivates with a dibenzopyran ring between two units, respectively. Dendrocandin H represents the first example of a bibenzyl derivative formed by a bibenzyl and a 1,4-phenanthraquinone unit via a dibenzopyran ring. Compounds 1-4 were examined for antioxidant activity by 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging assay.


Bone tissue engineering using polyetherketoneketone scaffolds combined with autologous mesenchymal stem cells in a sheep calvarial defect model.
Polyetherketoneketone (PEKK) a high performance thermoplastic polymer that is FDA-approved for cranio- and maxillo-facial as well as spineal surgery. We studied the viability, growth and osteogenic differentiation of bone marrow-derived human and sheep mesenchymal stem cells (MSC) in combination with a 3D scaffold made of PEKK using different cell-based assays. To investigate if autologous MSC, either undifferentiated or osteogenically pre-differentiated, augmented bone formation after implantation, we implanted cell-seeded 3D PEKK scaffolds into calvarial defects in sheep for 12 weeks. The volume and quality of newly formed bone were investigated using micro-computer tomography (micro-CT) and histological stainings. Our results show that the 3D PEKK scaffolds were cyto- and bio-compatible. They allowed for adherence, growth and osteogenic differentiation of human and ovine MSC. However, bone healing seemed unaffected by whether the scaffolds were seeded with MSC. Considerable amounts of newly formed bone were found in all PEKK treated groups, but a fibrous capsule was formed around the implants regardless of cell seeding with MSC.


Chemotherapy of acute leukemia in adults.
General therapeutic options for adult patients with acute leukemia are reviewed and specific new treatment strategies are described. Treatment results and controversial issues on current and future antileukemic strategies are discussed. Data in this review came from the published literature. In the past years, striking new developments have been noticeable in the treatment of adult acute leukemia. However, the overall outcome of adult acute leukemia remains poor, particularly in older patients. Intensive chemotherapy remains the standard for leukemia treatment but several approaches using new cytotoxic agents seem promising. Therapeutic targeting of specific biologic abnormalities present in the leukemia cell population might, in a near future, improve outcome of adult leukemia patients.


Polarization color imaging system for on-line quantitative evaluation of facial skin lesions.
A number of studies have been performed for accurate evaluation of chromophores in skin lesions. Qualitative methods are subjective and cause user-dependent error in evaluation. Quantitative methods have limitations for widely distributed skin lesions due to poor spatial resolution, potential skin blanching, and difficulty in relocating identical sites for subsequent measurements and analysis. The objective was to develop a new imaging modality that provides both qualitative and quantitative methods to evaluate widely distributed skin lesions. We have developed a prototype polarization color imaging system named "DermaVision," which provides quantitative on-line image analysis of polarization color images. Herein, we describe the hardware and software of DermaVision in terms of its performance and usefulness for dermatologic applications. Polarization color images were successfully acquired from patients with vascular or pigmented skin lesions. The erythema and melanin index images were successfully computed and quantitatively confirmed the degree of erythema and pigmentation in the skin lesions. We believe that DermaVision can be a useful auxiliary tool in dermatology because it simultaneously provides both qualitative and quantitative images of skin lesions.


The trouble with nouns and verbs in Greek fluent aphasia.
In the past verb retrieval problems were associated primarily with agrammatism and noun retrieval difficulties with fluent aphasia. With regards to fluent aphasia, so far in the literature, three distinct patterns of verb/noun dissociations have been described for individuals with fluent anomic aphasia in languages with different underlying forms; better verb retrieval, poorer verb retrieval and equal retrieval difficulties for verbs and nouns. Verbs and nouns in Greek are considered of similar morphological complexity thus it was predicted that anomic aphasic individuals would suffer from a non-dissociated impairment of verbs and nouns. Problems with verbs and/or nouns may arise at any stage in the process of lexical retrieval, i.e. lexical-semantic, lemma, lexeme or articulation. The aim of this research was to investigate verb and noun retrieval using a picture-naming task to explore any possible selective noun and/or verb comprehension or retrieval deficits in Greek individuals with anomic aphasia. The results revealed a significant verb/noun dichotomy with verbs significantly more difficult to retrieve than nouns. These findings lend support for the growing body of evidence showing a specific verb impairment in fluent anomic individuals as well as Broca's patients. Given the prevailing view, that anomic patients experience difficulty retrieving the morpho-phonological form of the target word, the results show that specific information of the grammatical category is also important during word form retrieval. LEARNER OUTCOMES: The reader will become familiar with (i) studies investigating grammatical word class breakdown in individuals with aphasia who speak different languages, (ii) the application of the serial model to word production breakdown in aphasia and (iii) the characteristics of verbs and nouns in Greek. It will be concluded that successful verb retrieval for fluent aphasic individuals who speak Greek is dependant on the retrieval of the morpho-phonological information of the target verb.


Echogenicity of Palmar Dupuytren's Nodules Is Not a Predictor of Disease Progression in Terms of Increase in Nodule Size.
Ultrasound might enable us to measure Dupuytren's disease activity and predict disease progression. The aim of this study was to analyze whether echogenicity of Dupuytren's nodules can be used to predict progression in terms of increase in nodule size. Ultrasonographic assessment of a Dupuytren's nodule was performed in 91 patients participating in an existing longitudinal cohort study. Images were scored for echogenicity by two observers. Echogenicity of 89 nodules was matched to growth 1 year later using linear regression analysis. Sensitivity analysis was performed using data obtained 1 year before ultrasound. The interobserver and intraobserver reliability was calculated using the intraclass correlation coefficient. Hypoechogenicity was not a predictor of growth 1 year later (beta = -0.019, p = 0.748). Sensitivity analysis looking at the year before ultrasonographic measurement showed that hypoechogenic nodules were more likely to have grown in the past year (beta = 0.173, p = 0.011). However, these data were influenced by nodules that developed in the year before ultrasound. The intraobserver reliability of echogenicity of Dupuytren's nodules was excellent (intraclass correlation coefficient, 0.996; 95 percent CI, 0.993 to 0.998) and the interobserver reliability was fairly good but imprecise (intraclass correlation coefficient, 0.688; 95 percent CI, 0.329 to 0.977). Hypoechogenicity is not a predictor of progression in terms of increase in nodule size measured by physical examination 1 year later. When using ultrasound to assess echogenicity of Dupuytren's nodules, the use of a single observer leads to more consistent results. Risk III.


Role of glutathione S-transferases in the spinocerebellar ataxia type 2 clinical phenotype.
Spinocerebellar ataxia type 2 (SCA2) is a neurodegenerative and incurable hereditary disorder caused by a CAG repeat expansion mutation on ATXN2 gene. The identification of reliable biochemical markers of disease severity is of paramount significance for the development and assessment of clinical trials. In order to evaluate the potential use of glutathione-S-transferase (GST) activity as a biomarker for SCA2, a case-control study in 38 affected, presymptomatic individuals or healthy controls was conducted. An enlarged sample of 121 affected individuals was set to assess the impact of GST activity on SCA2 clinical expression. There was a significant increase in GST activity in affected individuals relative to controls, although sensibility and specificity were not high. GST activity was not significantly influenced by sex, age, disease duration or CAG repeat size and did not significantly influence disease severity markers. These findings show a disruption of in vivo GST activity in SCA2, suggesting a role for oxidative stress in the neurodegenerative process.


Therapeutic monitoring of tacrolimus (FK506) with the first- and second-generation microparticle enzyme immunoassays: performance and results in four patient populations.
The performance of the first- and second-generation microparticle enzyme immunoassays for tacrolimus (Tacrolimus I and Tacrolimus II, respectively) was compared during 8 months routine drug monitoring. The minimum detection limit of the Tacrolimus II assay was lower: 1.4 versus 4.0 microg tacrolimus/l. There was also no overlap between results using 10 samples containing 0 and 1 microg tacrolimus/l in the Tacrolimus II assay (p < 0.001), with a corresponding significant difference achieved for the Tacrolimus I assay only at 0 and 4 microg/l. For control specimens, within-assay precision was superior for Tacrolimus II at 5 microg/l (7.3% vs. 31.5%), similar at 10 and 15 microg/l (6.3% versus 6.6% and 4.4% vs. 4.6%, respectively) but worse than Tacrolimus I at 25 microg/l (8.0% vs. 4.0%). Using three pools of blood samples from recipients of liver transplants (containing approximately 4, 10, and 20 microg tacrolimus/l) interassay precision (n > 20) was 14.2%, 10.4%, and 8.0% for Tacrolimus II and 42.4%, 13.8%, and 7.1%, for Tacrolimus I. The analytical times and stability of the calibration curves were similar for the two assays. Tacrolimus I and Tacrolimus II results were closely correlated using patients' blood samples (r approximately equal to 0.8 in 249 adult and 168 pediatric liver transplant samples, 161 renal transplant samples, and 61 samples from patients with autoimmune diseases). However, Tacrolimus II assay results were consistently lower (by a mean of 1.02 to 2.05 microg/l). The authors conclude that the Tacrolimus II assay retains the speed, accuracy, and precision of its predecessor and demonstrates an improved sensitivity, which should facilitate monitoring at less than 5 microg tacrolimus/l.


Dynamics of T cell memory in human cytomegalovirus infection.
Primary human cytomegalovirus (HCMV) infection of an immunocompetent individual leads to the generation of a robust CD4+ and CD8+ T cell response which subsequently controls viral replication. HCMV is never cleared from the host and enters into latency with periodic reactivation and viral replication, which is controlled by reactivation of the memory T cells. In this article, we discuss the magnitude, phenotype and clonality of the T cell response following primary HCMV infection, the selection of responding T cells into the long-term memory pool and maintenance of this memory T cell population in the face of a latent/persistent infection. The article also considers the effect that this long-term surveillance of HCMV has on the T cell memory phenotype, their differentiation, function and the associated concepts of T cell memory inflation and immunosenescence.


[The clinical case of the month. Cutaneous fascioliasis].
Fascioliasis is an hepato-biliary distomatosis which may exceptionally manifest itself in the skin. We report a case presenting as nodules localized on the trunk. Lesions cleared under praziquantel treatment.


Noses of the Middle East: Variety of Phenotypes and Surgical Approaches.
The Middle East (ME) proper, a vast area between the East coast of the Mediterranean Sea and Afghanistan, is populated by many nations and tribes. Several nose phenotypes are prevalent throughout the region, but there is no published study encompassing and exploring nose phenotypes encountered in the various countries and subregions of the ME. The current study was based on the analysis of compiled data from 1207 patients of ME origin (53% of my total rhinoplasty patient cohort) operated by the author during the years 1985 to 2015. Among them 1046 (86.5%) underwent primary rhinoplasty and 161 (13.5%) were previously operated elsewhere, almost all in the ME. The following nose subtypes were defined according to the data gathered during the duration of this study in the computerized medical charts and photo archives: Egyptian, Levantine, Turkish (Anatolian), oriental Turkish (Götürks of Central Asian origin), Iraqi, Kurdish, and Persian. From 1985 to 1994, 30% of my patients were of ME origin, from 2001 to 2013 60% and since 2014 65%. Prevalence of various ethnic origins among the patients seeking for rhinoplasty in Sweden was studied. Most frequently represented ethnic groups were quoted in the order of largest prevalence: Assyrians, Iraqis, Kurds, and Iranians. Technical peculiarities concerning surgery on the various ethnic groups were described. Noses of Middle Eastern populations exhibit some similarities, but also broad phenotypic variation. Consequently, there is no single typical Middle Eastern nose, although large size, prominent arched dorsum, and a naso-labial angle ≤90° are common.


Characterization of phospholipase A2 release by elicited-peritoneal macrophage and its relationship to eicosanoid production.
Elicited guinea pig peritoneal macrophages released a soluble phospholipase A2 (PLA2) into conditioned media that was biochemically and pharmacologically similar to the recombinant human (rh) type II 14 kDa PLA2. The level of activity found in the 24 h media positively correlated with cell number and was reduced by actinomycin D and cycloheximide suggesting the enzyme was being constitutively synthesized. The enzyme protein accumulated in the media over 10-24 h and remained at maximal levels over 40 h as demonstrated by both activity and ELISA measurements. This was preceded by an increase in total cell-associated sn-2-acylhydrolytic activity which reached maximal levels by 12-17 h of culture and remained elevated to 40 h. Treatment of cell homogenate with dithiothreitol (DTT) revealed a rise in DTT-insensitive sn-2-acylhydrolytic activity which increased between 12 and 24 h. Prostaglandin (PG) E2 but not leukotriene (LT)B4 accumulated in the media and reached maximal levels by 24 h. This paralleled the release of secreted type II 14 kDa-like PLA2 and the rise in DTT-insensitive cell-associated activity, but not upregulation and formation of new cyclooxygenase after aspirin treatment. Overnight exposure to a non-cell permeable selective 14 kDa PLA2 inhibitor or neutralizing mAb interfered with expression of PLA2 activity but not PGE2 accumulation over 24 h. This indicated that the secreted PLA2 was not directly involved in PGE2 biosynthesis. Exposure of the elicited macrophages to the cell permeable 14 kDa PLA2 inhibitor, 12-epi-scalaradial also did not effect PGE2 accumulation. Taken together, elicited guinea-pig macrophages release 14 kDa PLA2 upon culture, but this activity appears not to be related to the concomitant accumulation in PGE2. The role of the cell-associated PLA2 activity(s) in PGE2 formation cannot be ruled out.


Boundary condition effects on maximum groundwater withdrawal in coastal aquifers.
Prevention of sea water intrusion in coastal aquifers subject to groundwater withdrawal requires optimization of well pumping rates to maximize the water supply while avoiding sea water intrusion. Boundary conditions and the aquifer domain size have significant influences on simulating flow and concentration fields and estimating maximum pumping rates. In this study, an analytical solution is derived based on the potential-flow theory for evaluating maximum groundwater pumping rates in a domain with a constant hydraulic head landward boundary. An empirical correction factor, which was introduced by Pool and Carrera (2011) to account for mixing in the case with a constant recharge rate boundary condition, is found also applicable for the case with a constant hydraulic head boundary condition, and therefore greatly improves the usefulness of the sharp-interface analytical solution. Comparing with the solution for a constant recharge rate boundary, we find that a constant hydraulic head boundary often yields larger estimations of the maximum pumping rate and when the domain size is five times greater than the distance between the well and the coastline, the effect of setting different landward boundary conditions becomes insignificant with a relative difference between two solutions less than 2.5%. These findings can serve as a preliminary guidance for conducting numerical simulations and designing tank-scale laboratory experiments for studying groundwater withdrawal problems in coastal aquifers with minimized boundary condition effects.


Vestibular evaluation in children with otitis media with effusion.
Fifty per cent of children with serous otitis media may have some balance disturbances. To evaluate vestibular function in children with otitis media with effusion. The control group comprised 25 children with bilateral normal hearing and middle-ear function. The study group consisted of 30 children with bilateral otitis media with effusion; these were divided into 2 subgroups according to air-bone gap size. Measures included the Arabic Dizziness Handicap Inventory, an imbalance evaluation sheet for children, vestibular bedside tests for children, and air- and bone-conducted vestibular-evoked myogenic potential testing. Arabic Dizziness Handicap Inventory scores and some vestibular bedside test results were significantly abnormal, with normal video-nystagmography results, in children with otitis media with effusion. Air-conducted vestibular-evoked myogenic potentials were recorded in 73 per cent of children with otitis media with effusion, with significantly delayed latencies. Bone-conducted vestibular-evoked myogenic potentials were successfully detected in 100 per cent of children with otitis media with effusion with similar results to the control group. The Arabic Dizziness Handicap Inventory and vestibular bedside tests are valuable tools for detecting vestibular impairment in children. Bone-conducted vestibular-evoked myogenic potentials are useful for vestibular system evaluation.


[A case of invasive thymoma made resectable by preoperative chemotherapy].
A 25-year-old male patient of invasive thymoma was referred to our institute on March'95. He had night coughs and on the annual chest X ray exam a large tumor was found in antero-superior mediastinum. At first his tumor was too large to be resected and left brachiocephalic vein was completely occluded. By needle biopsy it was proved to be thymoma, therefore, preoperative chemotherapy was planned. The tumor responded well to the two courses of ADOC (ADM, CDDP, VCR, CAP) therapy and the tumor seemed to become resectable. In June operation was performed and the tumor was resected completely. It appears that in case of stage Ill invasive thymoma, preoperative chemotherapy is one of the choices although it seems unresectable.


Nontherapeutic use of antimicrobial agents in animal agriculture: implications for pediatrics.
Antimicrobial resistance is widespread. Overuse or misuse of antimicrobial agents in veterinary and human medicine is responsible for increasing the crisis of resistance to antimicrobial agents. The American Academy of Pediatrics, in conjunction with the US Public Health Service, has begun to address this problem by disseminating policies on the judicious use of antimicrobial agents in humans. Between 40% and 80% of the antimicrobial agents used in the United States each year are used in food animals; many are identical or very similar to drugs used in humans. Most of this use involves the addition of low doses of antimicrobial agents to the feed of healthy animals over prolonged periods to promote growth and increase feed efficiency or at a range of doses to prevent disease. These nontherapeutic uses contribute to resistance and create health dangers for humans. This report will describe how antimicrobial agents are used in animal agriculture and review the mechanisms by which such uses contribute to resistance in human pathogens. Although therapeutic use of antimicrobial agents in agriculture clearly contributes to the development of resistance, this report will concentrate on nontherapeutic uses in healthy animals.


Phase I study of a vaccine using recombinant vaccinia virus expressing PSA (rV-PSA) in patients with metastatic androgen-independent prostate cancer.
A Phase I trial of recombinant vaccinia prostate specific antigen (rV-PSA) in patients with advanced metastatic prostate cancer was conducted. This report describes 42 patients who were treated with up to three monthly vaccinations. All patients were entered on a dose-escalation phase I study of recombinant vaccinia containing the gene for PSA (rV-PSA). The primary objective of this study was to determine the safety of this vaccine in metastatic androgen-independent prostate cancer patients. A secondary objective was to assess evidence of anti-tumor activity by PSA measurements, radiologic findings, and immunologic methods. There was no significant treatment-related toxicity apart from erythema, tenderness, and vesicle formation that lasted several days at the site of injection in some patients. There were immunologic responses, in selected patients, as evidenced by an increase in the proportion of PSA-specific T cells after vaccination. Furthermore, we show that these patients' T cells can lyse PSA-expressing tumor cells in vitro. Given the low toxicity profile and the evidence of immunologic activity, we believe future study is warranted with PSA-based vaccines in prostate cancer. New PSA-based vaccines and vaccine strategies are currently being evaluated.


Paruresis (psychogenic inhibition of micturition): cognitive behavioral formulation and treatment.
Paruresis is a condition characterized by difficulty or inability to urinate in situations where others are present, or may soon be present. Despite knowledge that paruresis can significantly impact on occupational functioning, social functioning, and quality of life, there exists a paucity of research into effective treatments. Although cognitive conceptualizations have been advanced for other anxiety disorders, there has not been a comprehensive cognitive behavioral model of paruresis. This article presents a revised cognitive and behavioral conceptualization of paruresis, drawing on empirical evidence from other anxiety disorders. Using this conceptualization, a cognitive-behavioral intervention strategy is outlined, with clear targets for cognitive and behavioral strategies.


[Laparoscopic cystoprostatovesiculectomy and ureterosigmoidostomy. Experimental surgical model].
The authors have performed 26 experimental laparoscopic cystoprostatovesiculectomies in pigs, 17 of which were followed by ureterosigmoidostomies, also laparoscopically. Using a 10 mm trocar at the umbilical level (optics), another 10 mm at the hypogastric level (pliers and titanium staple applicator), a third 5 mm in left iliac fossa (pliers) and another 5 mm in right iliac fossa (electric shears), cystectomy is performed with a routine technique: stapling and section of deferents, umbilical arteries, vesical lateral pedicles and prostate-seminal pedicles. A double ligature precedes the section of the urethra in the pelvian fundus. A plier passed within an Amplatz jacket (previously introduced through the anus) assists the laparoscopic ureterosigmoidostomy "in elephant trunk" which is performed by sero-muscle suture using 3-zero reabsorbable single-strand material. Overcoming the anatomical differences existing with humans, the illustrated experimental model confirms the possibility of performing this type of procedures in human beings, which would considerably curtail the morbidity associated with this type of surgery.


Removal and recovery of uranium from aqueous solutions by Ca-alginate immobilized Trichoderma harzianum.
The ability of Ca-alginate immobilized Trichoderma harzianum has been explored for removal and recovery of uranium from aqueous streams. Ca-alginate as polymeric support was selected after screening different matrices. Immobilization of Trichoderma harzianum to Ca-alginate improved the stability as well as uranium biosorption capacity of biosorbent at 28+/-2 degrees C and 200 rpm. The suitability of packed bed column operations was illustrated by obtaining break through curves at different bed heights, flow rates and inlet uranium concentrations. The adsorption column containing 1.5 g dry weight of immobilized material has purified 8.5L of bacterial leach liquor (58 mg/LU) before break through occurred and the biosorbent became saturated after 25 L of influent. Sorbed uranium was recovered in 200 ml of 0.1N HCl resulting in 98.1-99.3% elution by 0.1N HCl, which regenerated the biosorbent facilitating the sorption-desorption cycles for better economic feasibility without any significant alteration in sorption capacity/elution efficiency.


Changes in prevalence and treatment need for traumatic dental injuries among 14-year-old children in Newham, London: a deprived area.
The study was carried out to assess the prevalence of traumatic injuries to the permanent incisors of 14-year-old schoolchildren in Newham in 1998-99, the treatment needed and to compare the results with data from 1995-96. Also, to test whether different levels of deprivation within an area would increase the risk of dental injury. A cross-sectional study was carried out. One dentist (SM) carried out all dental examinations. Upper and lower permanent incisors were examined for dental injuries. The examiner recorded the type of damage sustained, any treatment carried out and the treatment need. 411 14-year-old schoolchildren in Newham in 1998-99. Results The prevalence of traumatic injuries was 43.8% (95% CI 39.0, 48.7) in 1998-99, compared to 23.7% (95% CI 22.0, 25.5) in 1995-96. Boys sustained statistically significantly more dental injuries than girls, 50.2% and 37.1% respectively (P<0.01). In 1998-99 92.7 per thousand incisors were damaged, 6.7 per thousand incisors were treated and 28.9 per thousand incisors needed treatment. Two components of the Jarman Index were associated with dental injuries. Overcrowded household was statistically significantly related to dental injuries in both studies. Ethnicity was associated with dental injury in 1998-99, but not tested in 1995-96. CONCLUSIONS The prevalence of traumatic dental injury in Newham increased from 23.7% to 43.8% between 1995-96 and 1998-99, it was higher than the overall prevalence in the United Kingdom (17%) and its treatment had been neglected. Area-based measures of deprivation such as an overcrowded household and ethnicity were predictors of traumatic dental injuries.


Evaluation of commonly used tear sampling methods and their relevance in subsequent biochemical analysis.
The human precorneal tear film is a special body fluid, since it is a complex mixture of proteins, lipids, small bioactive molecules, and their concentrations and relative distribution represent not only the metabolic state of the ocular surface but also the systemic and local homeostasis of the outer eye and the human body. This suggests that biochemical analysis of the precorneal tear film composition may provide a non-invasive tool for diagnosis and monitoring of disease progression or treatment efficacy in human medicine. However, collecting tears is demanding, and obtaining reproducible and unaltered samples is challenging because of the small sample volumes of tears. Several methods are available for tear collection as a preparatory step of precorneal tear film analysis, and the collection method used has to be assessed since it has a critical impact on the effectiveness of the assays and on the quality of the results. Each sampling method has advantages and disadvantages; therefore, it is not easy to choose the appropriate collecting method for tear collection. To overcome these limitations various methods have been recommended by different authors for special aspects of specific tests. The aim of our review was to evaluate tear sampling methods with regard to our ongoing biochemical analysis. *Contributed equally.


Better differential diagnosis of iron deficiencyanemia from beta-thalassemia trait.
Iron deficiency anemia (IDA) and ß- Thalassemia Trait (ß-TT) are the most common forms of microcytic anemia. This study was conducted to compare the validity of these discrimination indices in differentiating ß- Thalassemia Trait (β-TT) from IDA by calculating their sensitivity, specificity and Youden's index. Totally 323 subjects (173 children and 150 adult) with microcytic anemia were involved in this study. We calculated 10 discrimination indices in all patients with IDA and β-TT. We divided the patients into two different groups as younger and older than 10 years. None of indices showed sensitivity and specificity of 100% in the patients older than 11 years, but only Shine and Lal Index showed sensitivity close to 90% and specificity of 100% in the patients younger than 10 years. The most accurate discriminative index for patients younger than 10 years was Shine & Lal and in case of patients older than 11 years it was RDWI. Youden's index for Shine & Lal & RBC Count and for RDWI & RBC Count indices has most diagnostic value for younger and older than 10 years, respectively. None of the indices was completely sensitive and specific in differentiation between β-TT and IDA. MCHD mean and median were very close to normal values for both IDA and β-TT patients, but in case of MHDL we have found mean and median were significantly higher than normal values in β-TT and lower than those in IDA patients. In our study, Youden's index of RBC and S & L were the highest and the most reliable discrimination indices in differentiating β-TT from IDA in the patients younger than 10 years and for patients older than 11 years, the most reliable discrimination indices were RBC and RDWI.


Tissue oxygen sensor function of NADPH oxidase isoforms, an unusual cytochrome aa3 and reactive oxygen species.
NADPH oxidase isoforms with different gp91phox subunits as well as an unusual cytochrome aa3 with a heme a/a3 relationship of 9:91 are discussed as putative oxygen sensor proteins influencing gene expression and ion channel conductivity. Reactive oxygen species (ROS) are important second messengers of the oxygen sensing signal cascade determining the stability of transcription factors or the gating of ion channels. The formation of ROS by a perinuclear Fenton reaction is imaged by 1 and 2 photon confocal microscopy revealing mitochondrial and non-mitochondrial generation.


Using a Standard Staffing Index to allocate nursing staff.
The Standard Staffing Index (SSI) was established as a method to determine unit staffing needs and allocate staff effectively. Daily staffing is based on the SSI, the average patient acuity, and the unit census. This has resulted in time savings to determine staffing needs and accurate monitoring of staffing patterns and productivity by nurse managers. The SSI is based on specific patient needs as determined by regular evaluations and audits.


Trauma center imaging problems: proposed solution with picture archiving communication systems.
Radiologic support for trauma center activities presents special problems that are discussed. This article proposed the use of a picture archiving communication system (PACS) as a potential solution. A sample PACS for this purpose is described to illustrate this approach.


Gynandroblastoma of ovary with juvenile granulosa cell component and heterologous intestinal type glands.
An ovarian gynandroblastoma in a 15-year-old girl is described. The predominant component was juvenile granulosa cell tumour. Areas of adult granulosa cell tumour and Sertoli cell elements were also present. Stromal theca and luteinised cells were identified. An additional histological finding was the presence of heterologous intestinal type glands. There was positive immunohistochemical staining of juvenile and adult granulosa cell areas with inhibin and MIC2 antibodies. Electronmicroscopy showed a close ultrastructural resemblance between tumour cells in granulosa and Sertoli cell areas, in spite of differences in architectural pattern, suggesting that both morphological components may derive from a single cell of origin. The tumour demonstrates a unique combination of elements which has not previously been described.


Chiral capillary electrophoretic method for quantification of apomorphine.
A new method for chiral determination of apomorphine enantiomers was developed and validated. Seven different neutral and charged cyclodextrins were tested for enantioselectivity on R,S-apomorphine. Sulfobutylether-beta-cyclodextrin was found to offer the best resolution, but with this system, four peaks were detected from a solution of the two enantiomers, which was suggested to be the result of different forms of the complex between the selector and apomorphine. A complexation constant was estimated for a complex of 1:1 ratio for the second and the fourth peak, whereas the other two peaks were fitted to a model ratio of 1:2 (analyte-selector). To avoid this phenomenon, hydroxypropyl-beta-cyclodextrin was then chosen as the chiral selector. An optimisation study was performed on three factors: concentration of the chiral selector, pH of the buffer, and applied voltage. Optimum conditions were: 14 mM of hydroxypropyl-beta-cyclodextrin, pH 3.0, and 16 kV. UV detection was at 200 nm. The method was validated at the chosen conditions, offering a limit of detection of 0.2 microM and a limit of quantification of 0.5 microM. The validated method was applied for the determination of R,S-apomorphine in a transport study with an in vitro cell culture model of the intestinal mucosa (Caco-2).


Effect of procyanidolic oligomers on corneal collagen of rabbits treated by excimer laser photoablation.
Procyanidolic oligomers (PCO) are mainly used for their therapeutic effect on the vascular wall. We could show that the mechanism of this effect involves interactions with mesenchymal cells and extracellular matrix (ECM). Recently we demonstrated in vitro that they also act on cornea, a tissue rich in ECM. For instance they stimulate the corneal biosynthesis of type VI collagen and proteoglycans. A potent antiprotease effect also could be demonstrated on corneas. In our present work we examined in vivo action of PCO on corneas. A group of rabbits received during 1 week on their right eye a treatment by procinaidolic oligomers, the left eyes were kept as controls. After 1 week both eyes underwent excimer laser photobalation. Another group of rabbits also received the PCO treatment on the right eye, not on the left, but was not treated by photoablation. One week after the surgical intervention corneas were collected and biochemical and morphological observations were carried out. Ocular administration of PCO was well tolerated and no toxic or inflammatory side-effects could be seen. In the control group photoablation was followed by a decrease of the content of corneas in type I collagen and a strong increase in type III collagen. On the corneas treated by PCO these alterations of the composition were not observed. These results indicate that PCO treatment before excimer laser photoablation maintains within normal limits the biochemical composition of the operated corneas.


The ROR nuclear orphan receptor subfamily: critical regulators of multiple biological processes.
The nuclear receptor superfamily, a group of structurally related, ligand-dependent transcription factors, includes a large number of orphan receptors for which no ligand has yet been identified. These proteins function as key regulators of many physiological processes that occur during embryonic development and in the adult. The retinoid-related orphan receptors (RORs) alpha, beta, and gamma comprise one nuclear orphan receptor gene subfamily. RORs exhibit a modular structure that is characteristic for nuclear receptors; the DNA-binding domain is highly conserved and the ligand-binding domain is moderately conserved among RORs. By a combination of alternative promoter usage and exon splicing, each ROR gene generates several isoforms that differ only in their amino terminus. RORs bind as monomers to specific ROR response elements (ROREs) consisting of the consensus core motif AGGTCA preceded by a 5-bp A/T-rich sequence. RORE-dependent transcriptional activation by RORs is cell type-specific and mediated through interactions with nuclear cofactors. RORs have been shown to interact with certain corepressors as well as coactivators, suggesting that RORs are not constitutively active but that their activity is under some regulatory control. RORs likely can assume at least two different conformations: a repressive state, which allows interaction with corepressor complexes, and an active state, which promotes binding of coactivator complexes. Whether the transition between these two states is regulated by ligand binding and/or by phosphorylation remains to be determined. Ca2+/calmodulin-dependent kinase IV (CaMKIV) can dramatically enhance ROR-mediated transcriptional activation. This stimulation involves CaMKIV-mediated phosphorylation not of RORs, but likely of specific nuclear cofactors that interact with RORs. RORalpha is widely expressed. In the cerebellum, its expression is limited to the Purkinje cells. RORalpha-/- mice and the natural RORalpha-deficient staggerer mice exhibit severe cerebellar ataxia due to a defect in Purkinje cell development. In addition, these mice have thin long bones, suggesting a role for RORalpha in bone metabolism, and develop severe atherosclerosis when placed on a high-fat diet. Expression of RORbeta is very restricted. RORbeta is highly expressed in different parts of the neurophotoendocrine system, the pineal gland, the retina, and suprachiasmatic nuclei, suggesting a role in the control of circadian rhythm. This is supported by observations showing alterations in circadian behavior in RORbeta-/- mice. RORgamma, which is most highly expressed in the thymus, plays an important role in thymopoiesis. Thymocytes from RORgamma-/- mice undergo accelerated apoptosis. The induction of apoptosis is, at least in part, due to a down-regulation of the expression of the antiapoptotic gene Bcl-XL. In addition to the thynic phenotype, RORgamma-/- mice lack lymph nodes, indicating that RORgamma is essential for lymph node organogenesis. Overexpression of RORgamma has been shown to inhibit T cell receptor-mediated apoptosis in T cell hybridomas and to repress the induction of Fas-ligand and interleukin 2. These studies demonstrate that RORs play critical roles in the regulation of a variety of physiological processes. Further characterization of the mechanisms of action of RORs will not only lead to the identification of ROR target genes and provide additional insight into their normal physiological functions, but will also determine their roles in disease.


[Role of CAAT/enhancer binding protein in IL-6 regulation of angiotensinogen gene expression].
Angiotensinogen is the only known precursor of vasoactive angiotensin II and also one of the acute phase proteins. This study was intended to understand the regulation of angiotensinogen gene expression induced by IL-6. Northern hybridization, electrophoretic mobility shift assay and transient transfections were conducted. Northern hybridization showed increase of angiotensinogen mRNA treated by IL-6 in Hep3B cells. Electrophoretic mobility shift assay further indicated the HAG IL-6RE homologous to IL-6 responsive element at -568 site of the angiotensinogen promoter binds C/EBP(CAAT/Enhancer Binding Protein). Consistent with this binding studies were the transient transfections of the expression vector in which 6 copies of HAG-IL-6RE linked to TK core promoter and fused to CAT reporter gene, revealing that C/EBPalpha was a transactivator under IL-6-induced condition. These observations suggest that C/EBP plays regulatory role in IL-6-induced angiotensinogen gene expression.


Using the theory of planned behavior to predict safer sexual behavior by ghanaian immigrants in a large midwestern U.S. city.
Ghanaian immigrant population in the United States is at a high risk for developing HIV/AIDS. This study uses the Theory of Planned Behavior to predict safer sexual behavior among Ghanaian immigrants in a large Midwestern city in the United States. A 55-item questionnaire was developed and tested for validity (face, content, and construct) and reliability (stability and test-retest). A total of 137 Ghanaian immigrants completed the questionnaire. The constructs of perceived behavioral control (p < 0.001) and subjective norm (p < 0.001) were significant predictors for intention to use condoms and they accounted for 38% of the variance. Behavioral intention for condom use (p < 0.001) was the significant predictor for condom use and it accounted for 21% of the variance. Health education interventions based on constructs of the Theory of Planned Behavior must promote consistent and correct use of condoms in this population.


Amyloidosis with oral involvement. Case report.
A patient with chronic renal failure was investigated after complaining of oral discomfort which was found to be due to macroglossia and generalized involvement of the oral soft tissues by amyloidosis. A search for multiple myeloma proved to be positive. She also had a previous history of Carpal-tunnel syndrome. Despite an initial good response to treatment with phenylalanine nitrogen mustard (melphalan hydrochloride), she finally succumbed to end-stage renal failure.


Differentiation of malignant lymphoma and non-lymphoma by an occlusive dressing method employing bromodeoxyuridine.
Although lymphoma cells can proliferate in skin tissue, lymphocytes which have infiltrated the skin due to inflammatory changes are generally unable to do so. It may be possible to differentiate malignant lymphomas from benign lymphocytic infiltrations in skin tissue by detection of cell cycle-related antigens. We developed a novel in vivo method for studying the cell kinetics of human skin using bromodeoxyuridine (BrdU) with an occlusive dressing. Following the application of BrdU, BrdU-labeled lymphoid cells were counted in the dermis. The patients studied included 22 with various types of lymphomas (lymphoma group) and 22 with different forms of inflammatory skin disease (non-lymphoma group). Skin specimens were obtained after applying occlusive adhesive plasters containing 2% BrdU dissolved in 0.9% sodium chloride solution and were then immunostained with anti-BrdU monoclonal antibody. The average percentages of labeled cells were 15.9 +/- 7.6% for the lymphoma group and 4.7 +/- 2.6% for the non-lymphoma group. This difference was statistically significant (p < 0.0001). Using this method, malignant lymphomas and benign lymphocytic infiltrations of the skin could be differentiated by counting BrdU-labeled lymphoid cells, and this method could help in determining a prognosis.


Origin of gas retention and symptoms in patients with bloating.
Patients reporting abdominal bloating exhibit impaired tolerance to intestinal gas loads. The aim of this study was to identify the gut compartment responsible for gas retention. In 30 patients predominantly reporting abdominal bloating (24 with irritable bowel syndrome and 6 with functional bloating) and 22 healthy subjects, gas (nitrogen, carbon dioxide, and oxygen) was infused into the intestine for 2 hours while measuring rectal gas outflow. First, in 12 patients and 10 healthy subjects, gas transit (24 mL/min jejunal infusion labeled with 74 MBq bolus of 133 Xe) was measured by scintigraphy. Second, in groups of patients and healthy subjects, the effects of gas infusion (12 mL/min) in the jejunum versus ileum, jejunum versus cecum, and jejunum versus sham infusion (n=6 each) were compared by paired tests. In patients, total gut transit of gas was delayed (50% clearance time, 33 +/- 4 min vs 23 +/- 4 min in healthy subjects; P <.05) owing to impaired small bowel transit (50% clearance time, 20 +/- 2 min vs 12 +/- 3 min in healthy subjects; P <.05), whereas colonic transit was normal (50% clearance time, 13 +/- 2 min vs 11 +/- 2 min in healthy subjects; not significant). Furthermore, jejunal gas infusion in patients was associated with gas retention (329 +/- 81 mL vs 88 +/- 79 mL in healthy subjects; P <.05), whereas direct ileal or colonic infusion was not (61 +/- 103 mL and -143 +/- 87 mL retention, respectively). In patients reporting bloating, the small bowel is the gut region responsible for ineffective gas propulsion.


Transport of proteins across the endoplasmic reticulum membrane.
The biosynthesis of many eukaryotic proteins requires their transport across the endoplasmic reticulum (ER) membrane. The process can be divided into two phases: (i) a targeting cycle, during which, by virtue of their signal sequences, nascent polypeptides are directed to translocation sites in the ER and (ii) the actual transfer of proteins across the membrane. The first phase has been well characterized, whereas the latter until recently was completely unresolved. Key components of the translocation apparatus have now been identified and it seems likely that they form a protein-conducting channel in the ER membrane. The transport process is similar to the process of protein export in bacteria.


Fetal growth and well-being.
Accurate monitoring of fetal growth is one of the most critically important components of prenatal care. Whether too large or too small for gestational age, the ramifications of abnormal fetal growth have both short-term and long-term sequelae for early neonatal life and beyond. Although not perfectly accurate, ultrasound and other monitoring technologies have markedly improved the ability to follow abnormalities of fetal growth and to decide if early intervention or early delivery is necessary. Clearly, perinatal morbidity and mortality are decreased with close surveillance of these at-risk fetuses.


The effects of fluency-evoking conditions on voicing onset types in persons who do and do not stutter.
Voicing onset changes between control conditions and three fluency-evoking conditions (choral reading [CHORAL], delayed auditory feedback [DAF], and noise [NOISE]) were studied in 12 persons who do not stutter and 10 who do stutter. Voicing onsets were distinguished physiologically using airflow prior to voicing, with zero airflow prevoicing categorized as hard and the rest as breathy. Persons who stutter were more fluent under all fluency-evoking conditions than control conditions. Speaking under fluency-evoking conditions did not significantly increase the overall proportion of breathy onsets from control conditions for either group. However, looking only at hard onsets in the control condition, we found that both groups changed significantly more to breathy (p = 0.001) under CHORAL and NOISE. In persons who stutter, onset type was not associated with whether a word was produced fluently or dysfluently in the control condition. Also, no relationship was found between onsets changing to breathy under fluency-evoking conditions and onsets changing to fluent. The results suggest that although fluency-evoking conditions can modify some voicing onset behaviors, these modifications do not relate to improvements in fluency.


Nostalgia: content, triggers, functions.
Seven methodologically diverse studies addressed 3 fundamental questions about nostalgia. Studies 1 and 2 examined the content of nostalgic experiences. Descriptions of nostalgic experiences typically featured the self as a protagonist in interactions with close others (e.g., friends) or in momentous events (e.g., weddings). Also, the descriptions contained more expressions of positive than negative affect and often depicted the redemption of negative life scenes by subsequent triumphs. Studies 3 and 4 examined triggers of nostalgia and revealed that nostalgia occurs in response to negative mood and the discrete affective state of loneliness. Studies 5, 6, and 7 investigated the functional utility of nostalgia and established that nostalgia bolsters social bonds, increases positive self-regard, and generates positive affect. These findings demarcate key landmarks in the hitherto uncharted research domain of nostalgia.


Homogeneity analysis in a Korte--Schmidt-type integrating gold sphere.
Homogeneity measurements in a gold-coated integrating sphere at eight wavelengths in the range from 400 to 2000 nm are presented and discussed. The inner sphere wall was scanned with a mirror-based internal sphere scanner at 288 different positions. The spatially resolved measurements show the transition from poor reflectivity, associated with large inhomogeneities at 400 nm, to high reflectivity in the infrared region at 2000 nm, associated with only small deviations. From the measurements the spectrally dependent relative uncertainty of the radiance of the inner sphere wall was deduced. A spectrally dependent sphere homogeneity correction factor F(lambda) relative to a specific point within the sphere wall was also derived.


Rapid elimination of cefaclor from the cerebrospinal fluid is mediated by a benzylpenicillin-sensitive mechanism distinct from organic anion transporter 3.
The purpose of this study was to investigate the carrier-mediated elimination of cephalosporins from the cerebrospinal fluid (CSF) via the choroid plexus. Cefaclor and cefalexin are structural analogs with similar lipophilicity, differing by only one functional group (cefaclor, -Cl; cephalexin, -CH(3)), and they are substrates of rat peptide transporter PEPT2 with similar transport activities. However, cefaclor was cleared from the CSF more rapidly than cefalexin after intracerebroventricular administration (the elimination rate constants were 0.11 and 0.050 min(-1), respectively). The elimination of cefaclor from the CSF was inhibited by benzylpenicillin, but not by glycylsarcosine (GlySar), whereas GlySar, but not benzylpenicillin, had an inhibitory effect on the elimination of cefalexin from the CSF. The uptake of cefaclor by the freshly isolated rat choroid plexus was saturable, with a K(m) value of 250 muM, and the uptake clearance corresponding to saturable components accounts for the major part of the in vivo clearance from the CSF (17 versus 26 mul/min, respectively). The uptake of cefaclor by the choroid plexus was inhibited by benzylpenicillin, but not by GlySar. However, the inhibitory effect of benzylpenicillin was weaker than expected from its own K(m) value, and furthermore, organic anion transporter (Oat)3 substrates (cimetidine or p-aminohippurate) had no effect. These results suggest that cefaclor and cefalexin are eliminated from the CSF by different transporters, and rapid elimination of cefaclor from the CSF is accounted for by a benzylpenicillin-sensitive mechanism distinct from Oat3. A slight modification of a single chemical group of cephalosporins can greatly affect the contribution of the transporters involved, and their duration in the CSF.


Aristolochic acid nephropathy revisited: a place for innate and adaptive immunity?
The histological features of aristolochic acid nephropathy (AAN) consist of paucicellular interstitial fibrosis, severe tubular atrophy, and almost intact glomeruli with media lesions of interlobular arteries. As an early phase of interstitial inflammation preceded peritubular fibrosis in the rat model of AAN, the aim was to investigate the presence of inflammatory cells in human AAN. Reports of confirmed cases and case series of AAN were reviewed in terms of interstitial inflammation and found to have very conflicting results. This prompted us to search for and characterize inflammatory cells within the native kidneys provided from four end-stage AAN patients. Prior aristolochic acid exposure was attested by the intrarenal presence of the typical aristolactam I-derived DNA adduct. Besides the tubulointerstitial lesions usually seen in the cortex, a massive infiltration of macrophages, T and B lymphocytes was detected by immunohistochemistry in the medullary rays and in the outer medullae with some extension to the upper cortical labyrinth. In parallel with histological findings reported in the rat model, inflammatory cells are present preferentially in the interstitium of the medullary rays and of the outer medulllae in renal interstitium from human AAN cases, even in the terminal stages. Further studies must be undertaken to determine the respective roles of innate and adaptive immunity in the progression of AAN.


[Immunotypes of Chlamydia trachomatis and the clinical picture of non-gonorrheal urethritis in men and cervicitis in women].
102 Chlamydia trachomatis isolates obtained from pregnant women and 42 isolates from man-consorts of women with chlamydial infection of cervix were immunotyped using a microimmunofluorescence (micro IF) with monoclonal antibodies kit (Washington Research Foundation, Seattle, USA). In both groups of patients the most common serovars were: E (37.3%) and D (24.6%) belonging to B-complex. Additional serovars noted were: F (11.3%), J (11.3%), I' (4.5%), I (3.5%, K (3.5%), G (2.8%) and H. Ba (both 0.2%). N. gonorrhoeae and/or T. vaginalis infections were more frequent from patients with B-complex Ch. trachomatis serovars (28/75 that is 37%) than C-complex Ch. trachomatis serovars (3/25 that is 12%).


Plasma and urine pharmacokinetics of free and of short-chain carnitine after administration of carnitine in man.
To 6 healthy volunteers 30 mg/kg of L-carnitine (1,3-hydroxy-4-N-trimethylamino-butyrate) were injected intravenously and plasma levels (mumol/l) of free and short-chain carnitine were determined at different times between 0.033 and 24 h. The urinary excretion of L-carnitine and short-chain carnitine in 24 h was also measured. After a period of wash-out the subjects received 100 mg/kg of L-carnitine orally and plasma levels were determined between 0.5 and 24 h. The urinary excretion of L-carnitine was measured for a period of 18.5-33 h after treatment. 3 of the volunteers also received 30 mg/kg of L-carnitine orally. Carnitine plasma levels were determined at different times between 0.5 and 18 h, while the urinary excretion of L-carnitine was measured for 48 h following the treatment. The results could indicate the presence of saturation phenomena in the absorption process for the oral doses used; specific research is required to ascertain this phenomena. The transfer of carnitine from central to extravascular volume is relatively rapid, as is its urinary excretion. The short half-life of carnitine and acetyl-carnitine can suggest the use of new forms of administration (slow-release).


The hemodynamic consequences of high-dose methohexital anesthesia in humans.
The hemodynamic, electroencephalographic (EEG), and metabolic effects of a high-dose methohexital anesthetic were examined in eight neurosurgical patients. The patients were studied at rest and at 15-min intervals during a 60-min infusion of the drug, given at a rate of 0.40 mg . kg-1 . min-1 (total dose 24 mg/kg). Ventilation was controlled with oxygen:air (FIO2 = 0.50), and fluid was infused at a rate sufficient to maintain pulmonary capillary wedge (PCW) pressures at control values (8 +/- 2 mmHg, mean +/- SD). Serum methohexital concentrations increased progressively, reaching values of 11.7 +/- 2.9 micrograms/ml at t = 30 min and 18.1 +/- 10.8 micrograms/ml at t = 60 min. Characteristic barbiturate-induced EEG changes were noted, with isoelectricity achieved at t = 28 +/- 13 min. Methohexital infusion resulted in significant reductions in arterial pressure (84% of control at t = 60 min), systemic vascular resistances (83% of control at t = 60 min), right and left ventricular stroke work indices (65% and 68% of control, respectively at t = 60 min), and total body O2 consumption (76% of control at t = 60 min). In addition, a progressive dose-related decrease in stroke volume index was noted (50.1 +/- 90 ml X beat-1 X m-2 at t = 0, 40.1 +/- 10.2 ml X beat-1 X m-2 at t = 60 [80% of control]). This occurred in spite of unchanged ventricular filling pressures.(ABSTRACT TRUNCATED AT 250 WORDS)


In vitro cytotoxicity induced by Clostridium perfringens isolate carrying a chromosomal cpe gene is exclusively dependent on sporulation and enterotoxin production.
Clostridium perfringens type A is a common source of food poisoning (FP) and non-food-borne (NFB) gastrointestinal diseases in humans. In the intestinal tract, the vegetative cells sporulate and produce a major pathogenic factor, C. perfringens enterotoxin (CPE). Most type A FP isolates carry a chromosomal cpe gene, whereas NFB type A isolates typically carry a plasmid-encoded cpe. In vitro, the purified CPE protein binds to a receptor and forms pores, exerting a cytotoxic activity in epithelial cells. However, it remains unclear if CPE is indispensable for C. perfringens cytotoxicity. In this study, we examined the cytotoxicity of cpe-harboring C. perfringens isolates co-cultured with human intestinal epithelial Caco-2 cells. The FP strains showed severe cytotoxicity during sporulation and CPE production, but not during vegetative cell growth. While Caco-2 cells were intact during co-culturing with cpe-null mutant derivative of strain SM101 (a FP strain carrying a chromosomal cpe gene), the wild-type level cytotoxicity was observed with cpe-complemented strain. In contrast, both wild-type and cpe-null mutant derivative of the NFB strain F4969 induced Caco-2 cell death during both vegetative and sporulation growth. Collectively, the Caco-2 cell cytotoxicity caused by C. perfringens strain SM101 is considered to be exclusively dependent on CPE production, whereas some additional toxins should be involved in F4969-mediated in vitro cytotoxicity.


The Endurant Stent Graft System: 15-month follow-up report in patients with challenging abdominal aortic anatomies.
The objective of this study is to report a 15-month follow-up with the Endurant Stent Graft System in patients with challenging aortic anatomies. At three German clinics, a consecutive series of 50 patients underwent endovascular abdominal aortic repair (EVAR) for challenging abdominal aortic aneurysm with the Endurant stent graft between November 2008 and May 2009. EVAR was elective in 48 cases and emergent in two. Patients had short (≤15 mm) aortic necks, severe suprarenal/infrarenal angulation, and/or small (<8 mm), calcified, severely angulated, or tortuous iliac or femoral access vessels. Additionally, a cohort of 40 patients without challenging anatomies were retrospectively analysed to clarify differences concerning technical success, mortality, and morbidity between these groups. The primary technical success rate was 92% (46/50). The 30-day mortality rate was 2% (1/50), the death due to multiorgan failure. Intraoperative angiograms revealed three type I endoleaks (2 proximal and 1 distal), and one of those was persisting at 30 days (30-day rate, 2%). Postoperative imaging discovered no further type I or type III endoleaks. The 30-day rate of the type II endoleak was 6% (3/50). There were two cases of graft limb occlusion, both requiring reintervention within 30 days. Follow-up was available in all of the 50 patients (100%) over a median of 15 months (1-25). During this time, seven patients died (overall mortality, 16%; 8/50), besides the above-described patient, all of them unrelated to the procedure. Compared to the 30-day results with the Endurant stent graft in non-challenging anatomies (no type I endoleak; no graft limb occlusion; all-cause mortality, 0%), procedure-related complications in challenging anatomies are increasing. Early and 15-month results with the Endurant stent graft in patients with challenging aortic anatomies are encouraging.


Elevated cerebrospinal fluid and serum nitrate and nitrite levels in patients with central nervous system complications of HIV-1 infection: a correlation with blood-brain-barrier dysfunction.
As nitric oxide (.NO) is hypothesised to play a role in the immunopathogenesis of neurological complications associated with inflammation, we compared levels of cerebrospinal fluid (CSF) and serum .NO metabolites in 24 patients with HIV-1 infection, to those in 58 non-HIV infected patients with neurological disorders. Levels of .NO metabolites were correlated with blood-brain-barrier dysfunction. CSF and serum nitrate and nitrite levels were measured by the nitrate reductase and Griess reaction methods. The .NO metabolites, nitrate and nitrite, were raised in the CSF and serum of patients with AIDS and central nervous system complications, when compared to non-HIV infected patients with inflammatory and non-inflammatory neurological disorders (median nitrate and nitrite: CSF=18.3 microM vs. 11.1 microM vs. 7.0 microM, P<0.001, and serum=53.8 microM vs. 50.3 microM vs. 41.4 microM, P=0.04, respectively). CSF nitrate and nitrite levels correlated with the albumin quotient. This study supports the evidence that .NO is a potential mediator of blood-brain-barrier breakdown in inflammatory diseases of the central nervous system.


Epidemiology and sociodemographic aspects of ocular traumatic injuries in Iran.
Although the incidence of ocular trauma has been clearly described in developed countries, few published data are available on the epidemiology and the effects of parameters that can influence the incidence and severity of ocular injuries in Iran. The present study tried to determine epidemiological aspects of ocular traumatic injuries and evaluate their effects on different types of ocular injury. The case series included 1950 consecutive patients with acute ophthalmic trauma presented to the emergency ward of Farabi Hospital in Tehran. Information was collected by interviewing patients and having them fill in a questionnaire. The final diagnosis was made by a medical resident. If there was a difficulty or doubt in diagnosis or classification, confirmation of diagnosis was made by senior faculty. Ocular injuries were classified into globe and non-globe injuries according to the site of injury. Mechanical globe injuries were classified according to Birmingham Eye Trauma Terminology (BETT) into closed and open injuries. The mean age of patients was 28.8 ± 12.8 years; 87.6% were male. The most common causes of injury were work-related (49.0%) and chance events (42.0%). The most frequent ocular injury was globe injury (95.6%), including mechanical (77.6% closed and 5.9% open), chemical (7.6%), photic (2.3%) and thermal (2.2%) injuries. Non-globe injury also occurred in 10.8% of patients; both globe and non-globe injuries occurred in 6.5% of patients. The hospitalization rate in all patients was 8.8%. Previous history of eye trauma was significantly more common in the group with isolated globe injuries (P < 0.001). History of eye trauma is a risk factor for globe injuries and female gender is a risk factor only for non-globe injuries. These two factors may predict future eye injury and increase its risk by 5.2 and 1.6 times, respectively.


Synthesis and biological activity of 5-alkyl-6-(alkylsulfanyl)- or 5-alkyl-6-(arylsulfanyl)pyrazine-2-carboxamides and corresponding thioamides.
Nucleophilic substitution of chlorine in 5-alkyl-6-chloropyrazine-2-carboxamides with various alkyl and arylthiolates afforded 20 5-alkyl-6-(alkylsulfanyl)- and 5-alkyl-6-(arylsulfanyl)pyrazine-2-carboxamides. The reaction of the amides with Lawesson's reagent yielded the corresponding thioamides. The assessment of in vitro antimycobacterial and antifungal activity of the compounds was carried out. In both series, the antimycobacterial activity increases with increasing molecular weight of the alkylsulfanyl group in position 6 of the pyrazine ring. Thioamides exhibited higher activity than the corresponding amides. 5-Butyl-6-(phenylsulfanyl)pyrazine-2-carbothioamide (2j) possessed the highest activity (91% inhibition) against Mycobacterium tuberculosis and also the highest lipophilicity (log P = 4.95). Only a poor in vitro antifungal effect was noted in 5-butyl-6-(butylsulfanyl)pyrazine-2-carboxamide (1i) and 6-(ethylsulfanyl)-5-isobutylpyrazine-2-carbothioamide (2q) against Trichophyton mentagrophytes and Absidia corymbifera.


Hedgehog signaling, epithelial-to-mesenchymal transition and miRNA (review).
SHH, IHH, and DHH are lipid-modified secreted proteins binding to Patched receptors, and CDON, BOC or GAS1 co-receptors. In the absence of Hedgehog signaling, GLI1 is transcriptionally repressed, GLI2 is phosphorylated by GSK3 and CK1 for the FBXW11 (betaTRCP2)-mediated degradation, and GLI3 is processed to a cleaved repressor. In the presence of Hedgehog signaling, Smoothened is relieved from Patched-mediated suppression due to the Hedgehog-dependent internalization of Patched, which leads to MAP3K10 (MST) activation and SUFU inactivation for the stabilization and nuclear accumulation of GLI family members. GLI activators then upregulate CCND1, CCND2 for cell cycle acceleration, FOXA2, FOXC2, FOXE1, FOXF1, FOXL1, FOXP3, POU3F1, RUNX2, SOX13, TBX2 for cell fate determination, JAG2, INHBC, and INHBE for stem cell signaling regulation. Hedgehog signals also upregulate SFRP1 in mesenchymal cells for WNT signaling regulation. Epithelial-to-mesenchymal transition (EMT) during embryogenesis, adult tissue homeostasis and carcinogenesis is characterized by class switch from E-cadherin to N-cadherin. SNAI1 (Snail), SNAI2 (Slug), SNAI3, ZEB1, ZEB2 (SIP1), KLF8, TWIST1, and TWIST2 are EMT regulators repressing CDH1 gene encoding E-cadherin. Hedgehog signals induce JAG2 upregulation for Notch-CSL-mediated SNAI1 upregulation, and also induce TGFbeta1 secretion for ZEB1 and ZEB2 upregulation via TGFbeta receptor and NF-kappaB. TGFbeta-mediated downregulation of miR-141, miR-200a, miR-200b, miR-200c, miR-205, and miR-429 results in upregulation of ZEB1 and ZEB2 proteins. Hedgehog signaling activation indirectly leads to EMT through FGF, Notch, TGFbeta signaling cascades, and miRNA regulatory networks. miRNAs targeted to stem cell signaling components or EMT regulators are potent drug targets; however, off-target effects should be strictly controlled before clinical application of synthetic miRNA. Peptide mimetic and RNA aptamer could also be utilized as Hedgehog signaling inhibitors or EMT suppressors.


Evidence for the use of l-methylfolate combined with antidepressants in MDD.
Helping patients with major depressive disorder achieve symptom-free remission with antidepressant therapy remains challenging. In this activity, 3 investigators discuss the results of a 2-trial, multicenter, randomized, double-blind, placebo-controlled study of adjunctive l-methylfolate, the bioavailable form of folate, in patients who had inadequately responded to an SSRI. The efficacy of doses of 7.5 mg/d versus 15 mg/d is examined, and the safety and tolerability of l-methylfolate are compared with those of other adjunctive treatments. Different types of folate are explained, and the characteristics of patients who might benefit from adjunctive l-methylfolate are proposed.


Prioritizing IVF patients according to the number of existing children--a proposed refinement to the current guideline.
The National Health Service is poised to offer at least one cycle of IVF treatment to couples free of charge in the UK, provided that certain clinical criteria are met. At a local level, therefore, funders are faced with the problem of prioritizing patients and establishing waiting lists. It is generally accepted that preference should be given to those with the 'greatest need', but it is uncertain what the criterion is for greatest need. We propose two recommendations as a modification to the current guideline that stresses the need to favour 'couples who do not have any children living with them'. First, we suggest that parental responsibility rather than shared residence be used as a criterion for eligibility. Second, we present a need-based approach that can be used coherently to distribute publicly funded treatment. In an attempt to achieve a fair way of prioritizing patients, we make distinctions between different family arrangements, based on the number of existing children. Our approach treats like cases alike, and ranks different cases relative to each other in a manner that is equitable and charitable.


Breast cancer in the information age: a review of recent developments.
Between 50 and 100 million Americans have used the Internet to obtain health information. Breast cancer is one of the most common diagnoses sought online, and breast oncologists are likely to encounter more and more patients who have used the Internet. The effects that this is having on patients and on the clinical encounter in oncology are unclear. Here, the author reviews recent research about the growing importance of online health information and the small amount of literature on breast cancer and the Internet. Other recent developments, such as efforts to recruit patients to clinical trials via the Internet and online support groups for cancer patients, also are reviewed. Finally, the author offers his views on how best to manage patients' growing interest in Internet information.


Antireflux surgery in Sweden, 1987-1997: a decade of change.
The aim of this study was to analyse whether new therapeutic options--the introduction of proton-pump inhibitors (PPI) in 1989 and the laparoscopic technique in 1992--altered the surgical treatment of gastro-oesophageal reflux disease (GORD) in Sweden. Data obtained from the Centre for Epidemiology (EpC) on patients undergoing surgery for GORD from 1987 to 1997 was analysed, and the information was validated with a questionnaire to all surgical departments. The questionnaire gave a response rate of 94%, and the figures corresponded well with those obtained from the EpC. In 1987, 456 antireflux procedures were performed. Ten years later this figure had increased to 1303. This approximately threefold increase started before the introduction of PPI and was even more pronounced during the following few years. The development of laparoscopic antireflux surgery did not alter this increase. In 1997, 76% of the procedures were performed laparoscopically. The fundoplication rate rose from 5.5 to 12.7 procedures/100,000 inhabitants. The rates varied greatly among different counties; 7 of 23 still had a fundoplication rate of less than 10 in 1997. The median number of procedures per hospital in 1997 was 10. Only two departments accomplished more than 50 antireflux procedures. Within 5 years the laparoscopic technique replaced the open procedure as the method of choice. However, the increase in the frequency of antireflux surgery was apparent even before the introduction of laparoscopy.


Analyses in human urothelial cells identify methylation of miR-152, miR-200b and miR-10a genes as candidate bladder cancer biomarkers.
Urinary miRNAs are discussed as potential biomarkers for bladder cancer. The majority of miRNAs, however, are downregulated, making it difficult to utilize reduced miRNA signals as reliable diagnostic tools. Because the downregulation of miRNAs is frequently associated with hypermethylation of the respective regulative sequences, we studied whether DNA hypermethylation might serve as an improved diagnostic tool compared to measuring downregulated miRNAs. miRNA expression arrays and individual qPCR were used to identify and confirm miRNAs that were downregulated in malignant urothelial cells (RT4, 5637 and J82) when compared to primary, non-malignant urothelial cells (HUEPC). DNA methylation was determined by customized PCR-arrays subsequent to methylation-sensitive DNA-restriction and by mass spectrometry. miRNA expression and DNA methylation were determined in untreated cells and in cultures treated with the demethylating agent 5-Aza-2'-deoxycytidine. miR-200b, miR-152 and miR-10a displayed differential expression and methylation among untreated cancer cell lines. In addition, reduced miRNA expression of miR-200b, miR-152, and miR-10a was associated with increased DNA methylation in malignant cells versus HUEPC. Finally, the demethylation approach revealed a causal relationship between both parameters for miR-152 in 5637 and also suggests a causal connection of both parameters for miR-200b in J82 and miR-10a in 5637. In conclusion, our studies in multiple bladder cancer cell lines and primary non-malignant urothelial cells suggest that hypermethylation of miR-152, miR-10a and miR-200b regulative DNA sequences might serve as epigenetic bladder cancer biomarkers.


Preparing marriage and family therapy students to become employee assistance professionals*.
While the number of Employee Assistance Programs (EAPs) has grown tremendously, opportunities for marriage and family therapists in EAP settings have not been adequately described. This paper addresses issues pertinent to training Marriage and Family Therapy (MFT) students to develop the skills needed to become EAP professionals. Qualifications for becoming an EAP professional are described and suggestions are made as to how these skills may be taught within the framework of an academically based MFT training program.


Dendritic cells: making progress with tumour regression?
Due to their potent ability to activate the immune system, dendritic cells (DC) are showing promise as potential adjuvants for tumour immunotherapy of cancer patients. However, little is known about the effect tumour cells can have on DC function. Indeed, the discovery of different DC subsets with different immunological functions indicates that the relationship between tumour cells and tumour-infiltrating DC subtypes is likely to be complex. There remains a lot to be understood about the effects of tumours on DC before we can expect to benefit from DC-based tumour immunotherapy of cancer patients. Here we review the recent advances being made in understanding DC phenotype and function in relation to interactions with different types of tumours.


[Prevalence of obesity in Spain: the SEEDO'97 study. Spanish Collaborative Group for the Study of Obesity].
The weight distribution of a random sample of Spanish population aged 25-60 years is described. The prevalence of obesity and overweight is estimated by sex, age group and cultural level. Weight, height and waist to hip ratio (WHR) were measured on 5,388 subjects aged 25-60 yr who participated in population Nutritional surveys carried out in four Spanish autonomous regions (Cataluña, País Vasco, Madrid and Valencia) from 1989 to 1994. They were pooled together in order to build a national random sample. The sample was classified according to body mass index (BMI) (weight in kg/height in m2). Obesity was defined as BMI > or = 30 kg/m2. The prevalence of obesity by sex, age group and cultural level was estimated. Risk values for WHR were defined as WHR > 1 for men and WHR > 0.9 for women. The prevalence of obesity was 13.4%, 11.5% among men and 15.2% among women. Obesity increased with age in men and women, from 5.3% in the 25-34 yr group to 26.3% in the age group 55-60. Among those with a BMI > or = 30, 30.7% of men and 25.1% of women had also risk values for WHR. Educational level showed an inverse relationship with obesity, thus obesity was higher in less educated groups, particularly among women (p < 0.001). The geographical distribution of obesity showed a south-southeast trend, significant for males (p < 0.001). Prevalence of obesity in Spain was 13.4%, higher after 45 yr of age, particularly in women and less educated groups.


Bites by the king cobra (Ophiophagus hannah) in Myanmar: successful treatment of severe neurotoxic envenoming.
Three patients bitten by the world's largest species of venomous snake, the king cobra (Ophiophagus hannah), were observed in Myanmar (Burma). All three were involved in the famous snake dance in Yangon (Rangoon) Zoological Gardens. One patient showed no signs of envenoming despite a sustained bite, another developed only signs of local envenoming, but in a third there was severe neurotoxic envenoming requiring mechanical ventilation for 64 1/2 hours, episodes of hypotension and massive swelling of the bitten limb. This patient showed some signs of recovery before delayed treatment with specific antivenom. It is possible that all three patients had some immunity to king cobra venom resulting from traditional 'immunization' achieved by scratching venom into the skin. The literature on king cobra bites is reviewed and recommendations given for antivenom and ancillary treatments.


Reduction in the microbial load on high-touch surfaces in hospital rooms by treatment with a portable saturated steam vapor disinfection system.
Recent scientific literature suggests that portable steam vapor systems are capable of rapid, chemical-free surface disinfection in controlled laboratory studies. This study evaluated the efficacy of a portable steam vapor system in a hospital setting. The study was carried out in 8 occupied rooms of a long-term care wing of a hospital. Six surfaces per room were swabbed before and after steam treatment and analyzed for heterotrophic plate count (HPC), total coliforms, methicillin-intermediate and -resistant Staphylococcus aureus (MISA and MRSA), and Clostridium difficile. The steam vapor device consistently reduced total microbial and pathogen loads on hospital surfaces, to below detection in most instances. Treatment reduced the presence of total coliforms on surfaces from 83% (40/48) to 13% (6/48). Treatment reduced presumptive MISA (12/48) and MRSA (3/48) to below detection after cleaning, except for 1 posttreatment isolation of MISA (1/48). A single C difficile colony was isolated from a door push panel before treatment, but no C difficile was detected after treatment. The steam vapor system reduced bacterial levels by >90% and reduced pathogen levels on most surfaces to below the detection limit. The steam vapor system provides a means to reduce levels of microorganisms on hospital surfaces without the drawbacks associated with chemicals, and may decrease the risk of cross-contamination.


Strain-specific immune response to Haemophilus influenzae in chronic obstructive pulmonary disease.
Previous studies of immune response to Haemophilus influenzae after exacerbations of chronic obstructive pulmonary disease (COPD) have yielded contradictory results. Using homologous (infecting) strains and immunoassays to surface-exposed epitopes, we tested the hypothesis that adults with COPD make new antibodies to strain-specific, surface-exposed epitopes on H. influenzae after exacerbations. We collected clinical information, sputum, and serum monthly and during exacerbations from 81 patients with COPD over 56 months. Serum antibodies to H. influenzae after exacerbations associated with H. influenzae in sputum were detected with whole bacterial cell ELISA and bactericidal assays. An immune response to homologous H. influenzae occurred after 22 of 36 (61.1%) exacerbations with newly acquired strains compared with 7 of 33 (21.2%) exacerbations with preexisting strains (odds ratio [OR] = 4.4; 95%, 1.8 to 10.8; p = 0.001). An absence of an immune response was strongly associated with complement sensitivity (OR = 0.03; 95% confidence interval, 0.003 to 0.22; p = 0.001). New bactericidal antibodies developed after exacerbations were highly strain specific, showing bactericidal activity for only 11 of 90 (12.2%) heterologous strains. Development of an immune response to H. influenzae supports its role in causing exacerbations. The strain specificity of the immune response likely represents a mechanism of recurrent exacerbations.


Advances in the molecular biology of gestational trophoblastic disease.
Gestational trophoblastic diseases are a heterogeneous pool of clinically and histopathologically defined entities with two clinically relevant features: reproductive failure and a high neoplastic potential. Here we review recent advances in understanding the biology and natural history of the most common form of trophoblastic disease, hydatidiform mole, with an emphasis on the clinical implications for patient management. There are no reliable genetic markers for predicting which subset of moles will behave aggressively, nor are there molecular diagnostic methods at present that offer advances over traditional histopathology. The predominant genetic finding in complete and partial hydatidiform moles is an imbalance of parental chromosomes, completely androgenetic (paternal) in the former and an extra paternal haploid set in the latter. This lack or imbalance of a maternal genomic contribution probably changes the gene expression since there is no evidence of gene mutation in these lesions.


Molecular characterization of a novel urea transporter from kidney inner medullary collecting ducts.
In the terminal part of the kidney collecting duct, rapid urea reabsorption is essential to maintaining medullary hypertonicity, allowing maximal urinary concentration to occur. This process is mediated by facilitated urea transporters on both apical and basolateral membranes. Our previous studies have identified three rat urea transporters involved in the urinary concentrating mechanism, UT1, UT2 and UT3, herein renamed UrT1-A, UrT1-B, and UrT2, which exhibit distinct spatial distribution in the kidney. Here we report the molecular characterization of an additional urea transporter isoform, UrT1-C, from rat kidney that encodes a 460-amino acid residue protein. UrT1-C has 70 and 62% amino acid identity to rat UrT1-B and UrT2 (UT3), respectively, and 99% identity to a recently reported rat isoform (UT-A3; Karakashian A, Timmer RT, Klein JD, Gunn RB, Sands JM, and Bagnasco SM. J Am Soc Nephrol 10: 230-237, 1999). We report the anatomic distribution of UrT1-C in the rat kidney tubule system as well as a detailed functional characterization. UrT1-C m RNA is primarily expressed in the deep part of the inner medulla. When expressed in Xenopus laevis oocytes, UrT1-C induced a 15-fold stimulation of urea uptake, which was inhibited almost completely by phloretin (0.7 mM) and 60-95% by thiourea analogs (150 mM). The characteristics are consistent with those described in perfusion studies with inner medullary collecting duct (IMCD) segments, but, contrary to UrT1-A, UrT1-C-mediated urea uptake was not stimulated by activation of protein kinase A. Our data show that UrT1-C is a phloretin-inhibitable urea transporter expressed in the terminal collecting duct that likely serves as an exit mechanism for urea at the basolateral membrane of IMCD cells.