Glutamatergic changes in the cerebral white matter associated with schizophrenic exacerbation.
Glutamatergic dysfunction in the brain has been implicated in the pathophysiology of schizophrenia. This study was aimed to examine several brain chemical mediators, including Glx (glutamate + glutamine), using (1)H magnetic resonance spectroscopy (MRS) in medicated patients with schizophrenia, with and without psychotic exacerbation. (1)H MRS was acquired in 24 patients with schizophrenia, with psychotic exacerbation; 22 patients without exacerbation; and 27 age- and sex-matched healthy volunteers. The levels of metabolites were measured in the left frontal and inferior parietal white matter and compared across the three groups. The Glx level was significantly elevated in the left inferior parietal white matter in the patients with psychotic exacerbation in comparison with that in the healthy volunteers and the patients without exacerbation (P < 0.05). We also detected that there was a significant correlation between Positive and Negative Syndrome Scale-positive scale and Glx level in the left parietal white matter (r = 0.51, P < 0.001). Higher than normal Glx levels indicate glutamatergic overactivity in the left inferior parietal white matter with schizophrenic exacerbation, a finding that is in accordance with the glutamatergic hypothesis in schizophrenia. The Glx level measured by (1)H MRS could be a biomarker for exacerbation in schizophrenia.


Epidemiological study of muscular disorders in Assiut, Egypt.
Few comprehensive epidemiological studies of the prevalence of muscle diseases have been undertaken, and none has been carried out in our locality. The present cross-sectional study was conducted in Assiut Governorate (Upper Egypt) to estimate the prevalence of different types of primary muscular disorder in 1997. The study involved 52,203 subjects, 15,617 (30%) from the rural community and 36,586 (70%) from the urban community. Patients were identified from a door-to-door survey, and all were subjected to a full clinical examination, with confirmation of the diagnosis through electrophysiological, and biochemical investigations. Histopathological studies were performed for the classification of muscular dystrophies. Forty patients with muscular disorders were identified, with a point prevalence of 76.6 per 100,000 in the total community with no significant differences between the rural and urban communities. The creatine kinase level was abnormally high (>225 IU/l) in 80% of the cases, increased in all patients with muscular dystrophy or myositis, in 88.8% of patients with systemic myopathy and 66.6% of patients with myotonia. None of the cases of myasthenia showed an increase in the creatine kinase level. The lifetime prevalence per 100,000 was 26.8 for muscular dystrophy, 11.49 for myotonia, 11.49 for myositis, 17.24 for systemic myopathy and 9.57 for myasthenia.


A co-ordinated network for radiation dosimetry (CONRAD): an overview.
The European Radiation Dosimetry Group (EURADOS) carried out a co-ordinated action, supported within the 6th Framework Programme of the European Commission entitled 'A Co-ordinated Network for Radiation Dosimetry (CONRAD)'. The project, executed from January 2005 to March 2008, yielded a large number of scientific results in different areas of dosimetry. This paper describes the objectives and general aspects of the project while the results are given in several contributions in this volume. Special consideration is given to the results and implications of the feasibility study for a sustainable network in radiation dosimetry, which was also carried out within the CONRAD project.


Urea cycle disorders in Thai infants: a report of 5 cases.
Urea Cycle Disorders (UCD) is an inborn error of urea synthesis in which ammonium and other nitrogenous precursors of urea accumulate leading to episodic coma and a high mortality rate. Therapy with peritoneal dialysis, essential amino acids or their nitrogen-free analogues has increased survival. The authors report 5 cases of urea cycle disorders, all of whom developed and were rescued from hyperammonemic coma. However, the eventual outcome was quite variable. Argininosuccinate lyase deficiency (ALD) Case 1. A 2 month old male infant, a product of a consanguineous marriage (Suphanburi province); developed poor feeding on day 7, lethargy, convulsion, hepatomegaly and respiratory alkalosis leading to respiratory failure and coma. Hyperammonemia, elevation of glutamic acid and argininosuccinic acid and its anhydrides confirmed the diagnosis of ALD. He is now 9 years old and severely retarded. Case 2. A male infant with history of lethargy, poor feeding on day 3, treated as sepsis and required respiratory support for 6 days; subsequently readmitted at age 2 weeks with vomitting, lethargy, seizure activity and hyperammonemia, and was treated by a local pediatrician in Songkhla province. There was a history of parental consanguinity and he was referred to Siriraj Hospital on day 64 with severe essential amino acid deficiency and acrodermatitis enteropathica with markedly elevated plasma citrulline level. In spite of aggressive treatment; the patient developed sepsis and he expired on day 78. Ornithine transcarbamylase deficiency (OTC) Case 3. An eleven-month-old male infant, the product of a non-consanguineous marriage, developed neonatal onset of hyperammonemia on day 5 after poor feeding, lethargy, hypothermia, seizure, apnea and coma. He was rescued from neonatal hyperammonemic coma on day 9 after aggressive treatment, but expired at eleven months of age after overwhelming sepsis. Case 4. A male infant, sibling of case 3 was referred to Siriraj Hospital on day 8 with hyperammonemia and coma. In spite of intensive genetic counseling given after the birth of their first child with OTC, the couple chose to have another baby without informing any physician. The baby developed vomiting and lethargy on day 2; subsequently hyperammonemia was noted. In spite of aggressive treatment given; hepatic dysfunction, renal failure and disseminated intravascular coagulation defects occurred on day 15. He expired on day 18 after parental permission for discontinuation of all treatment. Argininosuccinate synthetase deficiency (ASS) or Citrullinemia. Case 5. A seven week old female infant, the product of a consanguineous marriage and of Pakistani ethnic origin; developed intermittent vomiting from day 6. Initial diagnoses included ruminations, sepsis and pyloric stenosis for which she was operated on (day 30); however, vomiting continued; subsequently seizures, hyperammonemic coma developed and she was rescued from hyperammonemic coma within 30 hours. Significant elevations of citrulline and L-glutamine were demonstrated. She was discharged in excellent condition to her home in Dubai, the United Arab Emirates.


Does treatment of Helicobacter pylori infection reduce gastric precancerous lesions?
Treatment of Helicobacter pylori (H. pylori) decreases the prevalence of gastric cancer, and may inhibit gastric precancerous lesions progression into gastric cancer. The aim of this study was to determine the effect of treatment on subsequent gastric precancerous lesion development. We prospectively studied 27 patients who had low grade dysplasia at the time of enrollment, in addition to dysplasia atrophic gastritis and intestinal metaplasia observed in all patients. All were prescribed quadruple therapy to treat H. Pylori infection for 10 days. Patients underwent endoscopy with biopsy at enrollment and then at follow up two years later. Biopsy samples included five biopsies from the antrum of lesser curvature, antrum of greater curvature, angularis, body of stomach and fundus. RESULTS of these biopsies were compared before and after treatment. Overall, the successful eradication rate after two years was 15/27 (55.6%). After antibiotic therapy, the number of patients with low grade dysplasia decreased significantly (p=0.03), also with reduction of the atrophic lesions (p=0.01), but not metaplasia. Treatment of H. pylori likely is an effective therapy in preventing the development of subsequent gastric premalignant lesions.


A Survey on Mental Health Status of Adult Population Aged 15 and above in the Province of Ilam, Iran.
This research aims to determine the mental health status of population aged 15 and over in the province of Ilam in 2015. The statistical population of this cross-sectional field survey consisted of residents of urban and rural areas of Ilam in Iran. An estimated sample size of 1200 people was chosen using systematic random cluster sampling. The access was provided by the contribution of Geographical Post Office of Ilam, Dehloran and Eyvan cities. The General Health Questionnaire-28 (GHQ-28) was used as the screening tool for mental disorders. The analysis of data in the current study was carried out using the SPSS-18 software. Using GHQ traditional scoring method, the results showed that 32.4% of individuals (37% of females, and 28.1% of males) were likely to have a mental disorder. The prevalence of suspected cases of mental disorders was 33% in urban and 31% in rural areas. The prevalence of mental disorders was higher in females, people living in urban areas, those aged 65 years and above, divorced or widowed, illiterate, and the retired compared to other groups. In addition, the prevalence increased with age. The prevalence of anxiety and somatization symptoms was higher than social dysfunction and depression. Moreover, the prevalence of these symptoms was higher in females than males. Almost one third of the samples were likely to have a mental disorder. Therefore, the provincial authorities and health providers should take essential steps for providing and maintaining mental health services to promote community mental health.


Structural and functional differences between the two intrinsic zinc ions of Escherichia coli RNA polymerase.
DNA-dependent RNA polymerase (RPase) from Escherichia coli contains 2 mol of intrinsic Zn(II)/mol of core enzyme (alpha 2 beta beta'). In techniques analogous to those employed with the Zn(II) metalloenzyme aspartate transcarbamoylase [Hunt, J. B., Neece, S. H., Schachman, H. K., & Ginsberg, A. (1984) J. Biol. Chem. 259, 14793-14803], we show that titration of core or holoRPase with 10 or 16 equiv, respectively, of the sulfhydryl reagent p-(hydroxymercuri)benzenesulfonate (PMPS) results in the facile release of 1 mol of Zn(II) [B-site Zn(II)] in a reaction totally reversible with the addition of excess thiol provided no metal chelator is present. If ethylenediaminetetraacetic acid (EDTA) is present, reversal of the PMPS-enzyme complex results in formation of a Zn1 RPase [A-site Zn(II)]. This enzyme retains full transcriptional activity relative to Zn2 RPase on both calf thymus (nonspecific) and T7 (sigma-dependent, specific) DNA templates. If the core enzyme-PMPS complex is incubated with a large excess of another metal such as Cd(II) followed by thiol treatment, a hybrid ZnACdB RPase is formed. Direct treatment of the enzyme with excess Cd(II) also gives rise to a hybrid ZnACdB RPase. Transcription by these enzymes is also comparable to that of the starting Zn2 enzyme. Isolation of in vivo synthesized Co2 RPase and Cd2 RPase and treatment of either enzyme with PMPS/EDTA results in formation of a CoA and CdA enzyme, respectively. Co(II)A and Cd(II)A enzymes show 123 and 76%, respectively, of the elongation rates on T7 DNA observed for the Zn(II) enzyme. Visible absorption spectroscopy of the Co2 enzyme exhibits four d-d transition bands positioned at 760 (epsilon = 800), 710 (epsilon = 900), 602 (epsilon = 1500), and 484 (epsilon = 4000) nm. In addition, two charge-transfer bands are found at 350 (epsilon = 9600) and 370 (epsilon = 9500) nm. Only the Co(II) ion bound at site A is associated with this unique set of intense d-d transitions. The positions and intensities of both the visible and charge-transfer bands of Co(II)A RPase approximate those shown by Co(II)-substituted metalloenzyme sites where the ligands are four S rather than mixed S,N or S,O sites.


Importance of experience for older home care workers in facing up to the constraints of work.
Home care workers (HCWs) are at risk from injury. A case study was undertaken in a local community health center in order (1) to identify the constraints that introduce risk into the work of HCWs, and (2) to study the strategies they apply, depending on their age, to reduce the effects of those constraints. Observation and semistructured interviews were the main sources of data. Analysis shows that HCWs aged 45 or over sometimes adopt different postures from those used by their younger colleagues. During physical care, the HCWs also carry out screening and social support tasks that are not recognized in the organization of their work. Older workers develop strategies that help them save time, refine their screening and support methods, protect themselves against accidents, and react properly in emergencies or dangerous situations. Because the changes that can be made in patients' homes are limited, the expertise of experienced HCWs is essential. The organization of work must maintain a certain flexibility to allow the workers to use their strategies.


Enhanced expression of the β4-galactosyltransferase 2 gene impairs mammalian tumor growth.
Altered N-glycosylation of membrane proteins is associated with malignant transformation of cells. We found that the expression of the β4-galactosyltransferase 2 (β4GalT2) gene is decreased markedly during the transformation. Here, we examined whether the tumor growth activity of B16-F10 mouse melanoma cells can be reduced by the enhanced expression of the β4GalT2 gene. We isolated a clone, B16-β4GalT2, showing its β4GalT2 transcript 2.5 times higher than a control clone, B16-mock, by transducing its cDNA, and transplanted them subcutaneously into C57BL/6 mice to examine their tumor growth activity. The results showed that the average size of tumors formed with B16-mock cells is 13.1±0.76 mm, whereas that of tumors formed with B16-β4GalT2 cells is 5.1±1.13 mm (P<0.01) 2 weeks after transplantation. Immunohistochemical analyses showed that the apoptosis and the suppression of angiogenesis are induced in the tumors upon transduction of the β4GalT2 gene. To pursue a clinical usefulness of the β4GalT2 gene for suppressing human tumor growth, we injected adenoviruses carrying the human β4GalT2 cDNA into HuH-7 human hepatocellular carcinomas developed in severe combined immunodeficient mice, and observed marked growth retardation of the tumors. The enhancement of the β4GalT2 gene expression in tumors is one of the promising approaches to suppress human tumor growth.


Pseudotumor cerebri.
This paper reports the case of a 27-year-old obese female who presented for routine eye examination with bilateral disc edema. A preliminary diagnosis of pseudotumor cerebri was confirmed following neurologic examination. Causative mechanisms and treatment alternatives of this syndrome, as well as differential diagnosis of the swollen disc, will be discussed.


Relation between bone density and primary implant stability.
This study aims to relate bone density in Hounsfield units (Hu) with the primary implant stability measured by insertion torque (Ncm) and resonance frequency analysis (ISQ). Ten patients were included in this study. A total of 54 implant sites were provided from 10 computerized tomography scans. The computerized tomography scan was used for the preoperative evaluation of bone density for each patient. The bone mean density around planned implants was determined with Physioplanet TM software. Bone quality according resistance to drilling, insertion torque and resonance frequency measurements were recorded. A statistically significant relationship was observed between bone quality density and location with ISQ values. This research demonstrates a strong relationship between the bone density values from computerized tomography and the location in the maxillaries. A correlation exists between bone quality, according to the Lekholm & Zarb classification, and Hu computerized tomography values. The primary implant stability measured with resonance frequency analysis depends on bone density values, bone quality and implant location.


Essential role for Toll-like receptor 7 (TLR7)-unique cysteines in an intramolecular disulfide bond, proteolytic cleavage and RNA sensing.
Toll-like receptor 7 (TLR7) an innate immune sensor for microbial RNA, erroneously responds to self-derived RNA. To avoid autoimmune responses, TLR7 is suggested to be silenced until the N-terminal half of the TLR7 ectodomain (TLR7N) is cleaved off. Resultant truncated TLR7 (TLR7C) is thought to signal microbial RNA. We here show that TLR7N remains associated with TLR7C through a disulfide bond. By N-terminal amino acid sequencing, TLR7C was found to start at 461E or 462A. The newly established monoclonal anti-TLR7N showed that endogenous TLR7 in bone marrow-derived dendritic cells was almost all cleaved and cleaved TLR7N remained in endolysosomes. TLR7N in endolysosomes was linked with TLR7C by a disulfide bond. In contrast, TLR9 did not have a disulfide bond between TLR9N and TLR9C fragments. Among the cysteines unique to the ectodomain of TLR7 but not TLR9 (Cys98, Cys445, Cys475 and Cys722), Cys98 in TLR7N and Cys475 in TLR7C were required for an intramolecular disulfide bond. These cysteines were also needed for proteolytic cleavage of and RNA sensing by TLR7, but not for TLR7 trafficking from endoplasmic reticulum to endosomes. No response was seen in TLR7 mutants lacking the proteolytic cleavage site or TLR7C alone. These results demonstrate requirement for proteolytic cleavage and TLR7N in TLR7 responses and indicate RNA sensing by TLR7N + TLR7C.


Improved process for production of recombinant yeast-derived monomeric human G-CSF.
The human granulocyte colony-stimulating factor (hG-CSF) was efficiently secreted at high levels in fed-batch cultures of recombinant Saccharomyces cerevisiae. However, the secreted recombinant hG-CSF (rhG-CSF) was shown to exist as large multimers in the culture broth due to strong hydrophobic interaction. It was hardly monomerized even by urea at high concentration. This multimer has been reported to diminish specific receptor-binding activity of hG-CSF and causes undesirable problems in the downstream process. When the rhG-CSF was secreted to extracellular broth in the presence of a non-ionic surfactant (Tween 80) in the culture media, the multimerization of the secreted rhG-CSF was efficiently prevented in the fed-batch cultures. Also, the monomer fraction and secreted efficiency of rhG-CSF were significantly increased at the higher culture pH (6.5). Without using any denaturing agents, the secreted rhG-CSF monomer was easily purified with high recovery yield and purity via a simple purification process under acidic conditions, consisting of diafiltration, cation exchange, and gel filtration chromatography. A lyophilization process devoid of intermonomer aggregation was also designed using effective stabilizing agents.


The assessment of crowding without the need to record arch perimeter. Part I: Arches with acceptable alignment.
A simplified, mathematically determined technique for calculating arch perimeter (the overlap method) is described and its validity in determining an accurate assessment of crowding is tested. Indices, expressed in millimetres of crowding or spacing, were computed for both the whole arch and the labial segment alone. Study casts of 36 individuals with clinically acceptable lower arches were used to validate the method. The degree of crowding or spacing calculated was compared with a "clinical' assessment of each arch, in which the irregularity was measured directly using a steel ruler. Various calculation schemes were tested. Depending on exactly how the overlap was determined, the results varied slightly. Although the arches showed acceptable alignment, it was preferable to include a strategy for normalizing the positions of any rotated teeth before the overlaps were calculated. Repositioning any bucco-lingually displaced teeth into the line of the arch, however, was not useful. For the complete arch good agreement with the clinical assessment was reached on 31 occasions and for the labial segment, all but one appraisals were within 0.5 mm of each other. In the remaining instances (five complete arches and one labial segment), the degree of crowding or spacing was between 0.5 and 1 mm of the clinical assessment. Considering that clinical measurement of minor degrees of crowding and spacing cannot be precise, these results were considered acceptable. The method was easy to use, relying only on the recording of mesio-distal tooth widths and was acceptably reproducible. The technique would therefore appear to provide a valid yet simple research tool with which to record the degree of crowding. Its ability to cope with irregular and crowded arches will be the subject of a subsequent review.


A feminist critique of research on menopausal experience of Korean women.
Despite the increasing number of studies on the menopausal experience of Asian women, the focus of the studies has been on simple comparisons of their symptoms with Western women's and other disease-oriented research topics. To propose directions for future research on menopause, we analyzed and critiqued 158 studies on the menopausal experience of a group of Asian women-Korean women. The studies were retrieved through a search of computerized databases in the United States and South Korea, and they were reviewed, analyzed, and critiqued with a feminist perspective. Many of the studies have problems with (a) conceptualization, including ethnocentric and androcentric views of menopause, biomedical perspectives, and language difficulties; (b) research methods, such as inadequate instruments, passive relationships between researchers and research participants, culturally inappropriate communication styles, inadequate study designs, and homogeneous research participants; and (c) interpretation and communication of study findings. These issues undermine the conclusions drawn about the nature of the menopausal experience of Korean women.


Regional correlation of PET and CT in senile dementia of the Alzheimer type.
Alzheimer disease is manifested by both widespread and regionally restricted brain changes, some of which have recently been identified in vivo with computed tomography (CT) and positron emission tomography (PET). This is a report of the regional correlation of CT and PET measurements in 19 carefully diagnosed subjects comprising 11 controls and eight patients with senile dementia of the Alzheimer type. Regional CT attenuation values did not discriminate between the two groups, but PET using 18F-2-deoxy-2-fluoro-D-glucose demonstrated significant regional reductions (range, 21%-28%) in glucose utilization in the Alzheimer group. PET measures were also more consistently related to cognitive decline. The correlation between CT structural measures and PET metabolic measures demonstrated consistent relations between widespread PET regions and CT changes in the thalamus, posterior limb of the internal capsule, and temporal lobes. However, CT changes in the frontal white matter, caudate nucleus, and anterior limb of the internal capsule were not related to any regional PET changes. These data support previous findings of temporal lobe involvement in Alzheimer disease and suggest the involvement of structures in the region of the third ventricle.


Antenna organization in the purple sulfur bacteria Chromatium tepidum and Chromatium vinosum.
Structural aspects of the core antenna in the purple sulfur bacteria Chromatium tepidum and Chromatium vinosum were studied by means of fluorescence emission and singlet-singlet annihilation measurements. In both species the number of bacteriochlorophylls of the core antenna between which energy transfer can occur corresponds to one core-reaction center complex only. From measurements of variable fluorescence we conclude that in C. tepidum excitation energy can be transferred back from the core antenna (B920) to the peripheral B800-850 complex in spite of the relatively large energy gap, and on basis of annihilation measurements a model of separate core-reaction center units accompanied by their own peripheral antenna is suggested. C. vinosum contains besides a core antenna, B890, two peripheral antennae, B800-820 and B800-850. Energy transfer was found to occur from the core to B800-850, but not to B800-820, and it was concluded that in C. vinosum each core-reaction center complex has its own complement of B800-850. The results reported here are compared to those obtained earlier with various strains and species of purple non-sulfur bacteria.


In vivo effects of pregnancy-associated plasma protein-A, activin-A and vascular endothelial growth factor on other follicular-fluid factors during follicle deviation in mares.
During a follicular wave in mares, the two largest follicles (F1 and F2) begin to deviate in diameter when F1 is a mean of 22.5 mm. The intrafollicular effects of pregnancy-associated plasma protein-A (PAPP-A), IGF-I, activin-A and vascular endothelial growth factor (VEGF) on other follicular-fluid factors during deviation were studied. In four treated groups (n = 7/group), a single dose of one of the four factors was injected into F2 when F1 was > or = 20.0 mm (expected beginning of deviation). In a control group (n = 7), F2 was injected with vehicle. One day after treatment, a sample of follicular fluid was taken from F1 and F2 of the control group and from F2 of the treated groups and was assayed for free IGF-I, oestradiol, androstenedione, activin-A, inhibin-A, follistatin and VEGF. In the control group, the means for all end points were significantly greater in F1 than in F2, except that concentrations of androstenedione were lower in F1 than in F2. The treatment effects for F2 were significant as follows: PAPP-A increased the concentrations of free IGF-I, inhibin-A, follistatin and VEGF and decreased the concentrations of androstenedione; IGF-I increased the concentration of inhibin-A and decreased the concentration of androstenedione; activin-A decreased the concentrations of follistatin and androstenedione and increased the diameter of F2; and VEGF increased the concentration of IGF-I and decreased the concentration of androstenedione. These results support the hypotheses that during deviation in mares PAPP-A increases the follicular-fluid concentrations of free IGF-I, follistatin responds to changes in follicular-fluid concentrations of activin-A, and VEGF affects the concentrations of other follicular-fluid factors.


The metabolism and pharmacokinetics of 14C-cetirizine in humans.
This study investigated the metabolism and pharmacokinetics of cetirizine, a new H1-receptor antagonist. Single oral doses of 14C-cetirizine dihydrochloride (10 mg) in aqueous solution were administered to six healthy male volunteers. The drug was rapidly absorbed: The peak mean concentration of radioactivity (359 ng-equivalents/mL) and of unchanged drug (341 ng/mL) were achieved within one hour. Mean concentrations of cetirizine declined biexponentially and had a mean elimination half-life of 7.4 hours. The drug was excreted quite rapidly, with 60% of the dose recovered in the 24-hour urine. An additional 10% was excreted in urine over the next four days. Approximately 10% of the dose was excreted in feces over the five-day study period. The dose was excreted mainly as the unchanged drug. Examination of the radioactive compounds present in the plasma, and excreted in the urine and feces indicate that there is little metabolism of cetirizine. One minor metabolite, formed by oxidative O-dealkylation of the cetirizine side chain, was detected in plasma and feces.


Standardizing drug adverse event reporting data.
Normalizing data in the Adverse Event Reporting System (AERS), an FDA database, would improve the mining capacity of AERS for drug safety signal detection. In this study, we aim to normalize AERS and build a publicly available normalized Adverse drug events (ADE) data source.he drug information in AERS is normalized to RxNorm, a standard terminology source for medication. Drug class information is then obtained from the National Drug File - Reference Terminology (NDF-RT). Adverse drug events (ADE) are aggregated through mapping with the PT (Preferred Term) and SOC (System Organ Class) codes of MedDRA. Our study yields an aggregated knowledge-enhanced AERS data mining set (AERS-DM). The AERS-DM could provide more perspectives to mine AERS database for drug safety signal detection and could be used by research community in the data mining field.


Alanine transaminase levels in the year before pregnancy predict the risk of hepatitis C virus vertical transmission.
Vertical transmission is the most common route of hepatitis C virus (HCV) infection in children. Transmission risk factors have been described, but most risk factors can only be evaluated using expensive laboratory exams. The aim of the present study was to evaluate whether maternal alanine transaminase (ALT) levels before pregnancy correlate with HCV vertical transmission. Seventy-four transmitting and 403 nontransmitting mothers were evaluated. All mothers enrolled had two ALT determinations in the last year before pregnancy, at least 6 months apart. Mothers were divided into two groups: mothers with persistently normal serum ALT levels and mothers with abnormal ALT levels. In the second group both mothers with constantly raised or with fluctuating ALT levels (one normal and one raised determination) were included. ALT was defined as raised if higher than twice the upper limit of normal. Abnormal ALT levels were found in 39/74 (52.7%) HCV transmitting mothers and in 146/403 (32.6%) nontransmitting mothers (P = 0.008; relative risk 1.96; 95% confidence limits 1.19-3.23). The risk of transmission from mothers with constantly raised ALT levels was more evident than that from mothers with fluctuating ALT levels. Increased ALT levels may reflect a more severe liver disease and a higher viral load, factors known to be associated with vertical transmission. ALT determination, a simple, widely available and inexpensive test, may help in identifying mothers with an increased risk of HCV vertical transmission.


The biotransformation of the diterpene 2beta-hydroxy-ent-13-epi-manoyl oxide by Gibberella fujikuroi.
Incubation of the diterpene 2beta-hydroxy-ent-13-epi-manoyl oxide with Gibberella fujikuroi afforded in good yield 2beta,6beta-dihydroxy-ent-13-epi-manoyl oxide, 2beta,12beta-dihydroxy-ent-13-epi-manoyl oxide and 2beta,20-dihydroxy-ent-13-epi-manoyl oxide, confirming that although ent-13-epi-manoyl oxide is a final metabolite of a biosynthetic branch in this fungus, more polar derivatives of this compound can be transformed by this micro-organism.


How reliable are chance-corrected measures of agreement?
Chance-corrected measures of agreement are prone to exhibit paradoxical and counter-intuitive results when used as measures of reliability. It is demonstrated that these problems arise with Cohen's kappa as well as with Aickin's alpha. They are the consequence of an analogy to Simpson's paradox in mixed populations. It is further shown that chance-corrected measures of agreement may yield misleading values for binary ratings. It is concluded that improvements in the design and the analysis of reliability studies are a prerequisite for valid and pertinent results.


Bioequivalence of sodium monofluorophosphate with sodium fluoride and compatibility with calcium.
The study was conducted in a triple cross-over on 12 healthy Caucasian volunteers (4 males and 8 females) of an age between 23 and 44 years. The following products were given in a single oral dose in fasting state. 1. Solution of 29.18 mg of sodium fluoride in 80 ml of water (reference NaF solution). 2. Solution of 100 mg sodium monofluorophosphate (CAS 10163-15-2) in 80 ml of water (Na2FPO3 solution). 3. Tablets with 100 mg sodium monofluorophosphate and 1250 mg calcium carbonate (Na2FPO3 + Ca tablets). The three products were equivalent in fluorine content (13.2 mg). The bioavailability of fluorine was evaluated on the basis of the plasma levels and of the urinary excretion of fluoride. After administration of the products, fluoride appeared in blood with a lag time smaller than 0.05 h and invaded the blood with a t1/2 from 0.07 to 0.12 h. The Cmax of fluoride in plasma was 412-466 ng/ml at a tmax of 0.5-0.7 h. The AUCs of fluoride after Na2FPO3 solution and after Na2FPO3 tablets were within the 0.80-1.20 bioequivalence limits with regard to the AUC after NaF solution. The three products can therefore be considered bioequivalent according to the Westlake criteria. In the 24 h following the administration, the urinary excretion of fluoride accounted for 51 +/- 10%, 46 +/- 6% and 47 +/- 8% of the administered dose, respectively for NaF solution, Na2FPO3 solution and Na2FPO3 + Ca tablets. The difference between the three products was statistically not significant and confirms their bioequivalence.(ABSTRACT TRUNCATED AT 250 WORDS)


A national clinical scenario-based survey of clinicians' attitudes towards fresh frozen plasma transfusion for critically ill patients.
It is known that 20-30% of fresh frozen plasma (FFP) is used in intensive care units (ICUs), but little is known about variations in decision making between clinicians in relation to coagulopathy management. Our aim was to describe ICU clinicians' beliefs and practice in relation to FFP treatment of non-bleeding coagulopathic critically ill patients. Two patient-based scenarios were developed and sent to 2700 members of two UK intensive care professional societies. Scenario 1 was a non-bleeding septic patient with coagulopathy; scenario 2 was a non-bleeding critically ill patient with hepatic cirrhosis and coagulopathy. Responses were sought in relation to FFP prophylaxis, and prior to central venous cannulation. A supplementary question asked clinicians' view of prophylaxis in relation to other ICU procedures. Two-thousand-and-seven-hundred clinicians were surveyed from whom 601 responses were received (22·3% response rate). For scenario 1 52% of respondents stated that they would never routinely administer prophylactic FFP, but this decreased to 9% when central venous cannulation was planned (P < 0·01). There was wide variation in the 'trigger' INR (international normalised ratio) value used prior to central vein cannulation, the most common range being 2·0-2·4. For scenario 2, responses were very similar. More than 80% of clinicians stated that they would routinely treat coagulopathy prior to lumbar puncture, epidural catheterisation, intracranial pressure monitoring and tracheostomy; and 54% prior to chest drain insertion. Our survey demonstrated a wide range of responses consistent with important variations in clinical practice and substantial clinical uncertainty in relation to FFP treatment for non-bleeding ICU patients.


Therapy of solitary cecal diverticulitis in a young patient with laparoscopic right hemicolectomy.
Cecal diverticulum of colon is a relatively rare and benign condition in the western world. The reported frequency is approximately 1 in 300 appendectomies. They are usually asymptomatic but it may cause inflammatory, hemorrhagic, or perforatory complications. It is often clinically indistinguishable from acute appendicitis. The diagnosis is almost made intraoperatively. We present a 21-year-old female patient who admitted to our emergency unit with right lower quadrant abdominal pain. Diagnostic laparoscopy was performed due to suspicious acute appendicitis. During exploration, an inflammatory mass originated from cecum was noticed. Laparoscopic right hemicolectomy was performed due to suspicious malignant mass. The postoperative course was uneventful. Although radiologic techniques are improved; the diagnosis of solitary cecal diverticulum is difficult. The choice of surgical therapy is controversial. The therapy is ranged from a simple diverticulectomy to right hemicolectomy. Diagnostic laparoscopy can help the surgeon in the diagnosis of right lower quadrant pain and therapy of solitary cecal diverticulitis.


Safety and efficacy of 2% topical minoxidil in the management of male pattern baldness in Chinese.
Topic 2% minoxidil solution has been proved to be effective for hair regrowth in 30-40% of male pattern baldness in the United States and Europe. There was no report concerning topical minoxidil in Chinese patients, therefore, we selected 40 patients to investigate the efficacy and safety from December 1988 to January 1989. Those selected patients were consistent with male pattern baldness without systemic disease, and had never used topical hair regrowth agents. Patients applied topical medication 1 ml twice daily and were examined at 1 month intervals. Thirty two patients completed 6 to 12 months (average 9.6 months) of the study, moderate hair growth was found in 22% while minimal growth in 59% of the studied patients. All patients noted their shedding decrease after the application of drugs for 1 to 3 months. Scalp dryness and mild scaling appeared in 2 patients, but were tolerable. Before and after the trial, all patients had a chest roentgenogram, EKG, complete blood counts, urinalysis and blood chemistry studies, and no apparent abnormality was found. The efficacy of 2% minoxidil solution application in our study was less than that in the United States. which might be because some patients did not follow the application order regularly and a more strict evaluation standard was adopted in our series. However, the safety of no systemic adverse effect and the potential of inhibiting progressive shedding of hair were valuable as a topical drug.


The Influence of Traffic, Area Location, and Other Factors on Operating Room Microbial Load.
OBJECTIVE To determine how the movement of patients, equipment, materials, staff, and door openings within the operating room (OR) affect microbial loads at various locations within the OR. DESIGN Observation and sampling study. SETTING Academic health center, public hospital. METHODS We first analyzed 27 videotaped procedures to determine the areas in the OR with high and low numbers of people in transit. We then placed air samplers and settle plates in representative locations during 21 procedures in 4 different ORs during 2 different seasons of the year to measure microbial load in colony-forming units (CFU). The temperature and humidity, number of door openings, physical movement, and the number of people in the OR were measured for each procedure. Statistical analysis was conducted using hierarchical regression. RESULTS The microbial load was affected by the time of year that the samples were taken. Both microbial load measured by the air samplers and by settle plates in 1 area of the OR was correlated with the physical movement of people in the same area but not with the number of door openings and the number of people in the OR. CONCLUSIONS Movement in the OR is correlated with the microbial load. Establishing operational guidelines or developing OR layouts that focus on minimizing movement by incorporating desirable internal storage points and workstations can potentially reduce microbial load, thereby potentially reducing surgical site infection risk. Infect Control Hosp Epidemiol 2018;39:391-397.


Surgical pathology of carcinoid heart disease: a study of 139 valves from 75 patients spanning 20 years.
To quantitate the pathologic features of carcinoid plaques in a relatively large number of surgical specimens from a single institution. Medical records, operative reports, and surgical specimens were reviewed from all patients with carcinoid heart disease who underwent cardiac valvular surgery at Mayo Clinic, Rochester, Minn, between 1980 and 2000. The study group included 75 patients (45 men, 30 women) who ranged in age from 26 to 78 years (mean, 59 years). From these 75 patients, 139 valves had been excised surgically (73 tricuspid, 55 pulmonary, 6 mitral, 5 aortic). Pure regurgitation was the most common dysfunctional state of the tricuspid valve (80% [60/75]), mitral valve (97% [32/33]), and aortic valve (96% [23/24]). The pulmonary valve was more often both stenotic and insufficient (52% [37/71]) than purely regurgitant (30% [21/71]). In all cases, valve dysfunction was attributed to the presence of carcinoid plaques, which caused both thickening and retraction. Thickening was the result of both cellular proliferation and deposition of extracellular matrix. Proliferation of myofibroblasts was observed in all plaques and was mild in 49% (68/139) and moderate or severe in 51% (71/139). Extracellular matrix included collagen (in 99% of the 139 valves), myxoid ground substance (98% [136/139]), and elastin (20% [28/139]). Carcinoid plaques were also involved by neovascularization (94% [131/139]), chronic inflammation (94% [131/139]), and mast cell infiltration (64% [89/139]). Severe thickening was attributable primarily to collagen deposition in tricuspid valves and to myofibroblast proliferation and myxoid matrix in pulmonary valves. Among patients undergoing valvular surgery for carcinoid heart disease, tricuspid and pulmonary valves represented 92% of the excised valves (128/ 139). Although numerous cellular and extracellular features were common to the carcinoid plaques, variability in their relative expression produced appreciable differences in the histologic appearance among the plaques.


Static dynamics approach to relaxation modes and times for deformed polymers.
We discuss relaxation of conformational fluctuations around deformed polymer states. To this end, Brownian dynamics simulations of bead-spring models including a finite extensibility of the springs as well as excluded volume and hydrodynamic interactions between the beads have been performed. Complete spectra of relaxation times as well as corresponding relaxation modes are obtained from the simulation data by applying the static dynamics formalism, which rigorously describes the initial decay of correlations between the bead positions. As shown here, this procedure amounts to using a generalized Rouse-Zimm-like model which is governed by linear effective equations of motion having the same initial decay of correlations as the full nonlinear bead-spring model used in the simulations. In thermal equilibrium, the well-known scaling laws in the presence of excluded volume and hydrodynamic interactions between the beads are recovered, but, in addition, the static dynamics method also yields numeric values for the nonuniversal prefactors of the respective laws. The method is equally applicable to a broad range of problems, where the polymer is deformed by the action of flows or forces. Two examples of recent interest are considered: a tethered polymer pulled at its free end and one which is stretched by a uniform flow. It is shown that in both cases, the relaxation process is dominated by a finite extensibility of the springs.


The use of midazolam and diazepam for sedation following aorto-coronary bypass surgery.
The new water-soluble benzodiazepine midazolam was compared in a randomized study to diazepam for postoperative sedation in fifty patients following aortocoronary bypass surgery with a sufentanil-anesthesia. Midazolam and diazepam were administered intravenously in repeated doses in conjunction with an opioid infusion (piritramide) from the end of surgery during a twelve-hour study period, patients being artificially ventilated. Midazolam scored better than diazepam for quality of sedation and cardiovascular stability during the period of mechanical ventilation and for respiration during the weaning period and after extubation, although no difference was found in weaning time from artificial ventilation and time of extubation. Hemodynamic tolerance for both drugs was good. The administration of a loading dose of midazolam 5 mg caused a slight, transient decrease in mean arterial pressure. Midazolam appeared to be a more effective sedative agent than diazepam for short-term administration during mechanical ventilation. No evidence of cumulation and prolonged recovery was seen.


Keratinization of sheath and calamus cells in developing and regenerating feathers.
The present ultrastructural and immunocytochemical study on developing and regenerating feathers in the chick, zebrafinch and quail describes the formation of alpha-keratin cells in the sheath and their transition into beta-keratin cells in the calamus. In the first stages of feather formation cells are produced in the lower part of the follicle, migrate upward and form the elongating sheath of the feather filaments that grows outside the follicle. Sheath cells initially (anagen) contain bundles of alpha-keratin filaments. By the end of anagen at the base of the feather inside the follicle cells in continuation with the sheath produce homogenous bundles with the aspect of beta-keratin filaments. These bundles are immunoreactive for beta-keratin antibodies suggesting that beta-keratin is added to the initial framework of alpha-keratin. The packing of dense and hard corneous material in these cells eventually forms the calamus. The Latter corneous tissue replaces at the base of feathers the softer sheath present in more apical regions of the feather filaments. The increase of feather (beta)-keratin in cells of the calamus determines the formation of long bundles of corneous material. The modality of cornification in feathers is compared to the process of hard cornification of reptilian scales and claws and mammalian hairs and nails.


Effect of information load and time on observational learning.
We examined whether altering the amount of and moment when visual information is presented affected observational learning for participants practicing a bowling skill. On Day 1, four groups practiced a cricket bowling action. Three groups viewed a full-body point-light model, the model's bowling arm, or between-limb coordination of the model's left and right wrists only. Following retention tests on Day 2, all participants practiced after viewing a full-body display. Retention was again tested on Day 3. Bowling accuracy improved in all four practice groups. Kinematics of the bowling arm became more like the model for the full-body and intralimb groups only. All groups improved on measures of interlimb coordination. Visual search data indicated that participants mainly focused their gaze on the model's bowling arm. These data lead to the suggestion that viewing "end-effector" information (i.e., information pertaining to the bowling arm) is an important perceptual constraint early in observational learning. Implicit manipulations designed to increase attention to other sources of information did not facilitate the learning process.


Effect of methamphetamine on rat spinal cord. Dopamine receptor-mediated depression of monosynaptic reflex.
The experiments were performed on spinal rats transected at Cl. Intravenous administration of methamphetamine-HCl (MA-HCl, 2 mg/kg) and apomorphine-HCl (5 mg/kg) reduced the amplitude of the monosynaptic reflex (MSR), while the polysynaptic reflex was increased by methamphetamine. Depression of the monosynaptic reflex by both drugs was antagonized by haloperidol, but not by phentolamine. Depression of the monosynaptic reflex by methamphetamine was not antagonized by pretreatment with reserpine; however, the result was explained by the assumption that methamphetamine releases newly-synthesized dopamine or that methamphetamine may act directly on dopamine receptors. Depression of the monosynaptic reflex induced by methamphetamine was independent of peripheral changes in blood pressure. Oxygen tension in the spinal cord was slightly reduced by methamphetamine in rats treated with phentolamine and a change of pO2 in the spinal cord was ruled out as a possible mechanism of action. These results suggest that dopaminergic neurons in the spinal cord of the rat depress the transmission of monosynaptic spinal reflexes.


Causal variance decompositions for institutional comparisons in healthcare.
There is increasing interest in comparing institutions delivering healthcare in terms of disease-specific quality indicators (QIs) that capture processes or outcomes showing variations in the care provided. Such comparisons can be framed in terms of causal models, where adjusting for patient case-mix is analogous to controlling for confounding, and exposure is being treated in a given hospital, for instance. Our goal here is to help identify good QIs rather than comparing hospitals in terms of an already chosen QI, and so we focus on the presence and magnitude of overall variation in care between the hospitals rather than the pairwise differences between any two hospitals. We consider how the observed variation in care received at patient level can be decomposed into that causally explained by the hospital performance adjusting for the case-mix, the case-mix itself, and residual variation. For this purpose, we derive a three-way variance decomposition, with particular attention to its causal interpretation in terms of potential outcome variables. We propose model-based estimators for the decomposition, accommodating different link functions and either fixed or random effect models. We evaluate their performance in a simulation study and demonstrate their use in a real data application.


[Influence of culture medium osmolality on maturation and ovulation of Rana temporaria oocytes stimulated in vitro by the pituitary gland extract or progesterone].
The influence of diluted Ringer solution on ovulation and maturation of common frog oocytes stimulated in vitro by homologous pituitary extract (0.005 pit/ml) or progesterone (1 pg/ml) was studied. During wintering, the dilution of Ringer solution led to a decreased percentage of oocytes ovulated and matured under the influence of both inducers. As the season of reproduction approached, the dependence of oocyte maturation and ovulation on the Ringer solution dilution weakened. Possible causes of different dependence of the ovulation of amphibian and sturgeon oocytes stimulated by gonadotropic hormones or progesterone on the culture medium osmolality is discussed.


Clinicopathological Features and Prognosis of Gastrointestinal Stromal Tumor Located in the Jejunum and Ileum.
Data about the clinicopathological features and prognosis of gastrointestinal stromal tumors (GISTs) located in jejunum and ileum are lacking. The present study aims to investigate the features and prognosis of jejunal and ileal GISTs based on the Surveillance, Epidemiology, and End Results (SEER) database. Cases of jejunal and ileal GISTs were extracted from SEER database. Clinicopathological characteristics and survival data of patients were recorded. The clinicopathological features and prognosis of patients were analyzed. There were 399 male (56.8%) and 303 female (43.2%). The median age was 60 years (17-96). Four hundred and seventy-two tumors were located in the jejunum (67.2%) and 230 tumors in the ileum (32.8%). The median tumor size was 7.0 cm (0.5-90). The 5-, 10-, and 20-year disease specific survival (DSS) was 84.4, 71.2, and 54.2% respectively. Clinicopathological features were comparable between tumors located in the jejunum and ileum (all p > 0.05) except gender and tumor size (both p < 0.05). Jejunal GISTs, rather than ileal GISTs (p = 0.043), were commonly found in the males. The tumor size of jejunal GISTs was smaller than that of ileal GISTs (p = 0.010). The DSS of jejunal GISTs was comparable to that of ileal GISTs (p = 0.269). Jejunal GISTs were more common than ileal GISTs. The prognosis was comparable between jejunal and ileal GISTs.


Stishovite at the cretaceous-tertiary boundary, raton, new Mexico.
Stishovite, a dense phase of silica, has become widely accepted as an indicator of terrestrial impact events. Stishovite occurs at several impact structures but has not been found at volcanic sites. Solid-state silicon-29 magic-angle spinning nuclear magnetic resonance (silicon-29 MAS NMR) and X-ray diffraction of samples from the Cretaceous-Tertiary boundary layer at Raton, New Mexico, indicate that stishovite occurs in crystalline mineral grains. Stishovite was indicated by a single, sharp resonance with a chemical shift value of -191.3 ppm, characteristic of silicon in octahedral coordination, that disappeared after heating the sample at 850 degrees Celsius for 30 minutes. An X-ray diffraction pattern of HF residuals from the unheated sample displayed more than 120 peaks, most of which correspond to quartz, zircon, rutile, and anatase. Eight unambiguous weak to moderate reflections could be ascribed to d-spacings characteristic of stishovite.


Response to pediatric physical therapy in infants with positional preference and skull deformation.
Pediatric physical therapy seems to reduce skull deformation in infants with positional preference. However, not all infants show improvement. The study objective was to determine which infant and parent characteristics were related to responses to pediatric physical therapy in infants who were 2 to 4 months old and had positional preference, skull deformation, or both. This was a prospective cohort study. Infants who were 2 to 4 months old and had positional preference, skull deformation, or both were recruited by pediatric physical therapists at the start of pediatric physical therapy. The primary outcome was a good response or a poor response (moderate or severe skull deformation) at 4.5 to 6.5 months of age. Potential predictors for responses to pediatric physical therapy were assessed at baseline with questionnaires, plagiocephalometry, and the Alberta Infant Motor Scale. Univariate and multiple logistic regression analyses with a stepwise backward elimination method were performed. A total of 657 infants participated in the study. At follow-up, 364 infants (55.4%) showed a good response to therapy, and 293 infants (44.6%) showed a poor response. Multiple logistic regression analysis resulted in the identification of several significant predictors for a poor response to pediatric physical therapy at baseline: starting therapy after 3 months of age (adjusted odds ratio [aOR]=1.50, 95% confidence interval [95% CI]=1.04-2.17), skull deformation (plagiocephaly [aOR=2.64, 95% CI=1.67-4.17] or brachycephaly [aOR=3.07, 95% CI=2.09-4.52]), and a low parental satisfaction score (aOR=2.64, 95% CI=1.67-4.17). A low parental satisfaction score indicates low parental satisfaction with the infant's head shape. Information about pediatric physical therapy was collected retrospectively and included general therapy characteristics. Because data were collected retrospectively, no adjustment in therapy for individual participants could be made. Several predictors for responses to pediatric physical therapy in infants who were 2 to 4 months old and had positional preference, skull deformation, or both were identified. Health care professionals can use these predictors in daily practice to provide infants with more individualized therapy, resulting in a better chance for a good outcome.


Intraoperative radiation therapy using mobile electron linear accelerators: report of AAPM Radiation Therapy Committee Task Group No. 72.
Intraoperative radiation therapy (IORT) has been customarily performed either in a shielded operating suite located in the operating room (OR) or in a shielded treatment room located within the Department of Radiation Oncology. In both cases, this cancer treatment modality uses stationary linear accelerators. With the development of new technology, mobile linear accelerators have recently become available for IORT. Mobility offers flexibility in treatment location and is leading to a renewed interest in IORT. These mobile accelerator units, which can be transported any day of use to almost any location within a hospital setting, are assembled in a nondedicated environment and used to deliver IORT. Numerous aspects of the design of these new units differ from that of conventional linear accelerators. The scope of this Task Group (TG-72) will focus on items that particularly apply to mobile IORT electron systems. More specifically, the charges to this Task Group are to (i) identify the key differences between stationary and mobile electron linear accelerators used for IORT, (ii) describe and recommend the implementation of an IORT program within the OR environment, (iii) present and discuss radiation protection issues and consequences of working within a nondedicated radiotherapy environment, (iv) describe and recommend the acceptance and machine commissioning of items that are specific to mobile electron linear accelerators, and (v) design and recommend an efficient quality assurance program for mobile systems.


[Multiple sclerosis: new approaches to comprehensive treatment and rehabilitation using methods of reflexotherapy].
The article raises the question of integrated approaches to the treatment of multiple sclerosis, depending on the phase of the disease, type of course and comorbidity. The features of rehabilitation in this disease, discussed the feasibility of reflexology techniques in complex medical and rehabilitation measures.


A subpopulation of large granular von Willebrand Ag negative and CD105 positive endothelial cells, isolated from abdominal aortic aneurysms, overexpress ICAM-1 and Fas antigen.
The aim of this work was to determine whether there is a pre-established basal condition of the endothelial cells isolated from aortic abdominal aneurysm that might augment immune effector mechanisms and thus provide us an insight into the possible causes of aneurysm rupture. Endothelial cells isolated from saccular aortic aneurysm fragments were analyzed by cytofluorometry for the expression of different immune response-related molecules. Our results showed that there is a subpopulation of granule-rich, CD105 positive and von Willebrand antigen negative endothelial cells that have an enhanced basal expression of ICAM-1, and Fas antigen, but, interestingly, no apoptotic bodies were detected. Control endothelial cells derived from healthy areas of the same abdominal aortas did not show such enhanced expression. We conclude that in the endothelium that lines abdominal aorta aneurysms there is, at least, one endothelial cell subpopulation with an apparent inhibition of programmed cell death and in a proinflammatory activation status.


Pathway and carbon sources for hepatic glycogen repletion in dogs.
The present studies were undertaken to quantitate the relative contributions of the indirect and direct pathways for hepatic glycogen repletion and to determine the role of splanchnic tissues in provision of C precursors used for the indirect pathway. For this purpose, we administered oral glucose (1.4 g/kg) enriched with [1-14C]glucose to 18-h fasted dogs and measured net hepatic and net gastrointestinal glucose, lactate, and alanine balance, hepatic and gastrointestinal fractional extraction [( 3H]lactate), release and uptake of lactate, as well as the total amount of hepatic glycogen formed from the oral glucose and the 14C labeling pattern of the glycogen-glucose C. Although net hepatic glucose uptake (8.7 +/- 0.6 g, 27% of the oral load) exceeded the amount of glycogen formed from the oral glucose (6.3 +/- 1.1 g), analysis of radioactivity in C-1 of the glycogen glucose indicated that nearly 50% of the glycogen was formed by the indirect pathway. Net hepatic uptake of lactate (1.4 +/- 0.1 g) and alanine (1.5 +/- 0.1 g) could account for greater than 90% of glycogen formed by the indirect pathway if all of the lactate and alanine taken up by the liver had been incorporated into glycogen. Release of lactate and alanine by splanchnic tissues approximated the amount of lactate and alanine taken up by the liver. However, in addition to taking up lactate, the liver also produced nearly as much lactate as the gastrointestinal tract (1.8 +/- 0.2 vs. 2.0 +/- 0.3 g, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)


Basal cell carcinoma with pulmonary and lymph node metastasis causing death.
The incidence of metastatic basal cell carcinoma ranges from 0.003% to 0.55%. The 230 reported cases most often occurred in long-standing recurrent lesions and appeared in regional nodes or the lungs. The stromal dependence of the tumor provides an explanation for the nonmetastasizing nature of basal cell carcinoma. The dense fibrous stroma of the lymph node in the case of metastatic basal cell carcinoma reported in the present study is similar to other reported cases with metastases to lymph nodes, bone, bone marrow, glands, and subcutaneous tissue. This metastatic basal cell carcinoma demonstrated lymphatic and hematogenous dissemination to the lungs and lymph nodes. A dense accumulation of microvessels was present at the boundary of the tumor nests and dermal stroma and in the stroma surrounding the tumor in the lymph node.


Cross-species difference in telomeric function of tankyrase 1.
Telomeres protect chromosome ends from being recognized as DNA double-strand breaks. Telomere shortening, which occurs due to incomplete replication of DNA termini, limits the proliferative capacity of human somatic cells and contributes as a barrier to carcinogenesis. In most human cancer cells, telomerase maintains telomere length whereas TRF1, a telomeric protein, represses telomere access to telomerase. Tankyrase 1 is a PARP that dissociates TRF1 from telomeres by poly(ADP-ribosyl)ating TRF1. Thus, by reducing TRF1 loading on chromosome ends, tankyrase 1 enhances telomere access to telomerase and causes telomere elongation. Recent studies of knockout mice suggest that tankyrases may not regulate telomere length in mice (Mus musculus). Consistent with this idea is that mouse TRF1 has no canonical tankyrase-binding motif. However, the presence of such a motif is not a prerequisite to bind tankyrase 1 in certain species. Here, we found that, in mice, tankyrase 1 does not bind or poly(ADP-ribosyl)ate TRF1. Accordingly, mouse TRF1 was resistant to tankyrase 1-mediated release from telomeres. These observations indicate that telomeric function of tankyrase 1 is not conserved in mice. We also found that the canonical tankyrase 1-binding motif in TRF1 is conserved in several mammals but not in rats. Since mice and rats have much higher telomerase activity in their somatic tissues and much longer telomeres than those in other mammals, these rodent species might have evolved to resign the tankyrase 1-mediated telomere maintenance system. Meanwhile, PARP inhibitors induced non-telomeric tankyrase 1 foci in the nuclei, suggesting another function of tankyrase 1 at non-telomeric loci.


Purification and characterization of VanR and the cytosolic domain of VanS: a two-component regulatory system required for vancomycin resistance in Enterococcus faecium BM4147.
Resistance to the glycopeptide antibiotic vancomycin requires five genes. Two of these, vanR and vanS, have sequence homology to cytoplasmic response regulatory (VanR) and transmembrane sensory (VanS) proteins of two-component regulatory systems used to sense and transduce environmental signals. We report the overproduction and purification to homogeneity of VanR (27 kDa) and of a fusion protein of VanS (residues 95-374, the cytosolic domain) to the maltose binding protein (MBP), yielding a MBP-VanS protein of 76 kDa. The MBP-VanS fusion protein displayed an ATP-dependent autophosphorylation on a histidine residue with a rate of 0.17 min-1 and a phosphorylation stoichiometry of 10-15%. 32P-PhosphoMBP-VanS transferred the phosphoryl group to VanR. 32P-Phospho VanR showed chemical stability anticipated for an aspartyl phosphate and was relatively stable to hydrolysis (t1/2 = 10-12 h). Thus, the vancomycin resistance operon appears to have collected and specifically tailored the His kinase and Asp phosphoryl receptor of two-component signal transduction logic for sensing extracellular vancomycin and turning on structural genes, vanA and vanH, to make altered peptidoglycan structures such that vancomycin does not bind.


[Reticular activation by splanchnic afferents: its influence on visual projections at the level of the cerebral cortex in cats].
In an previous work, we have shown a strong increase of visual evoked potentials of the medial lateral gyrus by splanchnic stimulation. This present study demonstrates that this effect is due to the activation of the substantia reticularis. Actually, we observed: 1) an increase of the reticular visual potential by splanchnic stimulus in convergent zone; 2) an increase of the visual evoked potential in the primary cortical area by stimulation of this reticular formation. These results show the existence of a functional pathway including the splanchnic nerve, the reticular formation and the visual cortex.


Fussy eating and feeding difficulties in infants and toddlers consuming a cows' milk exclusion diet.
Cows' milk allergy (CMA) is the most common infant food allergy in the United Kingdom, requiring a strict exclusion diet. Feeding difficulties and fussy eating are also very common problems in young children and can negatively influence feeding and dietary intake in an infant with CMA. The aim of this study was to compare the levels of fussy eating and feeding difficulties in two groups of young children: a group consuming an exclusion diet for CMA and a control group of children consuming an unrestricted diet. Participants were recruited from allergy and health visitor clinics on the Isle of Wight. Parents completed a number of questionnaires about their child's feeding behaviour. One hundred and twenty-six participants (mean age 13 months) were recruited. Participants consuming an exclusion diet for CMA had significantly higher scores for both fussy eating and feeding difficulties (p < 0.05), although overall both groups were within the normal range. A number of symptoms were found to be positively moderately correlated with higher feeding difficulty score (p < 0.05). A higher consumption of milk/milk substitute consumed per day was positively correlated to both feeding difficulties and fussy eating (p < 0.05). Participants consuming an exclusion diet for CMA have higher scores for feeding difficulties and fussy eating than those consuming an unrestricted diet; however, the majority of participants' scores were within the normal range and did not affect the growth.


Quantified partial embolisation in a vein of galen malformation with congestive cardiac failure.
The aim of the study was to quantify embolisation in a vein of Galen malformation by intraluminal measurements of flow velocities in the feeding vessels and to test a new O.014-inch Doppler guide wire in the paediatric population. The examination was performed in a seven month old boy who presented with a vein of Galen malformation combined with congestive cardiac failure from birth. The measurements showed a decrease of the systolic and diastolic velocities and an increase in the effective downstream vascular resistance after closure of the high flow fistula. The decrease of the diastolic velocities after embolisation was more prominent because of the reduction of the sump effect responsible for the high diastolic velocity before embolisation. The reduction of about 40% of the vein of Galen malformation estimated with morphological criteria was associated with a decrease of the diastolic velocity in the basilar artery of about 50%. The clinical improvement led to the discontinuance of most of the cardiac treatment over a few days. These measurements seem to offer the possibility to assess the necessary reduction of the shunt to relieve CCF in a vein of Galen malformation.


Effect of TMAO and betaine on the energy landscape of photosystem I.
The accumulation of organic co-solvents in cells is a basic strategy for organisms from various species to increase stress tolerance in extreme environments. Widespread representatives of this class of co-solvents are trimethylamine-N-oxide (TMAO) and betaine; these small molecules are able to stabilize the native conformation of proteins and prevent their aggregation. Despite their importance, detailed experimental studies on the impact of these co-solvents on the energy landscape of proteins have not yet been carried out. We use single-molecule spectroscopy at cryogenic temperatures to examine the influence of these physiological relevant co-solvents on photosystem I (PSI) from Thermosynechococcus elongatus. In contrast to PSI ensemble spectra, which are almost unaffected by the addition of TMAO and betaine, statistical analysis of the fluorescence emission from individual PSI trimers yields insight into the interaction of the co-solvents with PSI. The results show an increased homogeneity upon addition of TMAO or betaine. The number of detectable zero-phonon lines (ZPLs) is reduced, indicating spectral diffusion processes with faster rates. In the framework of energy landscape model these findings indicate that co-solvents lead to reduced barrier heights between energy valleys, and thus efficient screening of protein conformations can take place.


A new anthracycline antibiotic, IT-62-B, converts the morphology of ras-transformed cells back to normal: taxonomy, fermentation, isolation, structure elucidation and biological characterization.
A new antibiotic, IT-62-B was isolated from the culture broth of Streptomyces sp. IT-62 by extraction with acetone and then with ethyl acetate, followed by conventional column chromatography using silica gel, Sephadex LH-20 and silica ODS. Its structure (C39H47NO15, MW 769) was determined by 1H, 13C NMR, MS, IR and UV spectrometric techniques to be a new member of the baumycin-group anthracyclines. It showed moderate activity against Gram-positive bacteria and had antitumor activity against various tumor cell lines. Further, antibiotic IT-62-B converted the morphology of ras-transformed NIH3T3 cells and T-cells back to normal at concentrations inhibiting cell growth by 30% or more.


Receiver operating characteristic curve inference from a sample with a limit of detection.
The receiver operating characteristic curve is a commonly used tool for evaluating biomarker usefulness in clinical diagnosis of disease. Frequently, biomarkers being assessed have immeasurable or unreportable samples below some limit of detection. Ignoring observations below the limit of detection leads to negatively biased estimates of the area under the curve. Several correction methods are suggested in the areas of mean estimation and testing but nothing regarding the receiver operating characteristic curve or its summary measures. In this paper, the authors show that replacement values below the limit of detection, including those suggested, result in the same biased area under the curve when properly accounted for, but they also provide guidance on the usefulness of these values in limited situations. The authors demonstrate maximum likelihood techniques leading to asymptotically unbiased estimators of the area under the curve for both normally and gamma distributed biomarker levels. Confidence intervals are proposed, the coverage probability of which is scrutinized by simulation study. An example using polychlorinated biphenyl levels to classify women with and without endometriosis illustrates the potential benefits of these methods.


Immune and clinical outcomes in patients with stage IV melanoma vaccinated with peptide-pulsed dendritic cells derived from CD34+ progenitors and activated with type I interferon.
Twenty-two HLA A*0201 patients with stage IV melanoma were enrolled in a phase 1 safety and feasibility trial using a composite dendritic cell (DC) vaccine generated by culturing CD34 hematopoietic progenitors and activated with IFN-alpha. The DC vaccine was loaded with peptides derived from four melanoma tissue differentiation antigens (MART-1, tyrosinase, MAGE-3, and gp100) and influenza matrix peptide (Flu-MP). Twenty patients were evaluable, 14 of whom received vaccination with peptide-pulsed DCs without keyhole limpet hemocyanin (KLH) and 6 of whom received vaccination with KLH-loaded DCs. Patients were vaccinated until disease progression or until they had received eight vaccinations. None of the analyzed patients showed the expansion of melanoma-peptide-specific circulating effector memory T cells that secrete IFN-gamma in direct ELISPOT. Melanoma-peptide-specific recall memory CD8 T cells able to secrete IFN-gamma and to proliferate could be detected in six of the seven analyzed patients. There were no objective clinical responses. The estimated median overall survival was 12 months (range 2-38), and the median event-free survival was 4 months (range 1-12). There was no statistically significant survival advantage in patients who received KLH-loaded vaccines. As of March 2005, four patients remained alive, 26+, 28+, 28+, and 36+ months. Three of them had received KLH-loaded vaccines and all of them had had additional therapy. Overall, these results suggest that IFN-alpha-activated CD34-DCs are safe but elicit only limited immune responses, underscoring the need to test different DC maturation factors.


Occupational therapist: OTR/manager.
Occupational therapists become more involved in management/administrative skills as they progress profesionally; however, varying degrees of these same skills are used by the therapist at every work level and in every work environment. Operational management skills may include applying and implementing policy on the part of the supervising therapist, or may include organization of time as well as management of supplies and persons by a therapist for effective and efficient productivity. Administrative management skills, forming and interpreting policy, are also needed on every work level. The effectiveness of all management/administrative skills is dependent on the institutional or organizational structure within which the therapist works. Occupational therapists must acquire an understanding of organization and administration, how structure affects function, and how to apply management skills in the everyday work situation in order to produce their best professional effort.


How does stigma affect people with mental illness?
People with mental health problems experience many different types of stigma. This article explores the attitudes and beliefs of the general public towards people with mental illness, and the lived experiences and feelings of service users and their relatives.


Aequorin-expressing mammalian cell lines used to report Ca2+ mobilization.
Mammalian cells that stably express jellyfish aequorin have been used to report activation of Ca2+ mobilization by cell-surface receptors. Expression of aequorin cDNA (pAEQ) was driven by the cytomegalovirus (CMV) promoter in CHO-K1 and 293 cells. Clonal isolates were obtained which express high levels of apo-aequorin protein, the Ca(2+)-dependent luminescence of which is generated by treatment of living cells with the coelenterate luciferin, coelenterazine. Transient expression of aequorin in COS cells results in even greater abundance of luminescent protein. Aequorin protein is lost from digitonin-permeabilized cells to the same extent and at the same rate as lactate dehydrogenase (LDH), indicating cytosolic location of the indicator. Aequorin expressing cells treated with agonists of endogenous receptors were used in luminescence measurements to demonstrate that the reporter lines offer a highly sensitive and robust means of assaying changes in the concentration of cytosolic Ca2+ ion. Transient co-expression of the substance P receptor in aequorin reporter cells was also performed to demonstrate the feasibility of using this convenient and sensitive assay system for large scale screening of ligands that activate cell surface receptors coupled to increases in intracellular Ca2+.


Polymerization shrinkage-strain and microleakage in dentin-bordered cavities of chemically and light-cured restorative materials.
The aim of this study was to evaluate in vitro the relationship between polymerization shrinkage and microleakage in dentin-bordered restorations. Four light-cured restorative materials in combination with their respective dental bonding agents (DBA) were investigated: Tetric Ceram/Syntac classic (Vivadent), Solitaire/Gluma Solid bond (Heraeus Kulzer), Definite/Etch & Prime 3.0 (Degussa), Solitaire 2/Gluma Solid bond (Heraeus Kulzer). The chemically cured resin Degufill sc microhybrid (Degussa) in combination with ART Bond (Coltène) was also included. Polymerization shrinkage of the restorative materials was measured using three different methods (dilatometer, linometer, buoyancy method) and analyzed with ANOVA. For the determination of microleakage, caries-free human molars were embedded in acrylic resin and subsequently abraded with a wet abrasion machine to produce four level dentin surfaces. One hundred sixty cavities (3 mm diameter/1.5 mm deep) were randomly assigned to four groups of equal size. The groups were restored without (group 1 and 2) and with DBA (group 3 and 4), and either not subjected (group 1 and 3) or subjected (group 2 and 4) to 2000 cycles from 5-55 degrees C. Each group was further divided into five material subgroups of eight cavities each. Microleakage was determined using a dye penetration test assessed at depths of 200, 400 and 600 microm into the fillings. Data were analyzed with the Kruskal-Wallis and the Mann-Whitney test. All three methods of measuring polymerization shrinkage (PS) generated the same, statistically secured ranking for the four light-cured restorative materials: PS Definite < PS Tetric Ceram < PS Solitaire 2 < PS Solitaire. In the microleakage study, only a few statistically significant differences were observed. Etch & Prime 3.0/Definite in group 3 and Solid Bond/Solitaire 2 in group 4 tended to exhibit the least microleakage. Correlation coefficients between aggregated shrinkage and microleakage data were 0.3 for group 3 and -0.2 for group 4. The results do not suggest any correlation between polymerization shrinkage and microleakage in dentin of direct adhesive restorations.


Molecular characterization of resistance, virulence and clonality in vancomycin-resistant Enterococcus faecium and Enterococcus faecalis: A hospital-based study in Beijing, China.
The incidence of vancomycin-resistant enterococcus (VRE) in China is increasing, the molecular epidemiology of VRE in China is only partly known. This study was conducted to assess the molecular characterization of resistance, virulence and clonality of 69 vancomycin-resistant Enterococcus faecium (VREfm) and seven vancomycin-resistant Enterococcus faecalis (VREfs) isolates obtained from a Chinese hospital between July 2011 and July 2013. The glycopeptide resistance genes (VanA and VanB) were screened by multiplex PCR. The presence of five putative virulence genes (esp, gelE, asa1, hyl and cylA) were evaluated by another multiplex PCR. Multilocus sequence typing (MLST) scheme was used to assess the clonality. All 76 VRE isolates exhibited VanA phenotype and harbored VanA gene. Esp was the only gene detected both in VREfm and VREfs strains, accounting for 89.9% and 42.9%, respectively. The hyl gene was merely positive in 27.5% of VREfm strains. MLST analysis demonstrated three STs (ST6, ST4 and ST470) in VREfs and twelve STs (ST78, ST571, ST17, ST564, ST389, ST18, ST547, ST341, ST414, ST343, ST262 and ST203) in VREfm, which were all designated as CC17 by eBURST algorithm. An outbreak of VREfm belonging to ST571 was found to happen within the neurology ward in this hospital. To our knowledge, this is the first report of ST6 (CC2) VREfs strains in China and the first outbreak report of VREfm strains belonging to ST571 around the world. Our data could offer important information for understanding the molecular features of VRE in China.


Brain oedema and cellular changes induced by acute heat stress in young rats.
Exposure of young animals (70-80 g, Age 6-7 weeks) to heat stress (HS) at 38 degrees C for 4 h in a B.O.D. incubator (rel humid 50-55%, wind vel 28.6 cm/sec) resulted in a 4.41% increased brain water content from the control value. Morphological studies in parietal cerebral cortex at light microscopical level revealed chromatolysis and appearance of dark neurons. Electron microscopy of similar regions showed perivascular oedema, vacuolation and collapsed microvessels. The swelling of astrocytes and of postsynaptic membranes was frequent. A diffuse infiltration of lanthanum (La[NO3]3) in endothelial cell cytoplasm and in the vesicles was very common. Occasionally, the lanthanum was seen in the basement membrane but the tight junctions were mainly intact. At this time period, a significant increase in blood-brain barrier (BBB) permeability as well as 5-HT levels in brain and plasma were observed. Pretreatment with p-CPA (a 5-HT synthesis inhibitor) prevented the increase of brain water content. BBB permeability and 5-HT levels in brain and plasma. Cyproheptadine (a 5-HT2 receptor antagonist) treatment significantly reduced the occurrence of increased brain water content and the BBB permeability. The 5-HT level continued to remain high. These results point out a probable role of 5-HT in pathophysiology of HS via 5-HT2 receptors.


Changes in arterial and transcutaneous oxygen and carbon dioxide tensions during and after voluntary hyperventilation.
The purposes of our study were (1) to investigate whether a 3-min short-term hyperventilation leads to posthyperventilatory hypoxemia and (2) to assess the role of transcutaneous blood gas measurements for monitoring oxygen and carbon dioxide changes during the after the test. In 10 male volunteers arterial and transcutaneous blood gases were measured simultaneously before, during and after a 3-min voluntary hyperventilation maneuver. Baseline arterial PO2 increased from 13.7 +/- 0.4 kPa (103 +/- 3 mm Hg) to 18.6 +/- 0.3 kPa (139 +/- 2.3 mm Hg; p < 0.005 compared to baseline) during hyperventilation. After the provocation test posthyperventilatory hypoxemia occurred with a minimal mean value of 7.8 +/- 1.3 kPa (58.5 +/- 9.8 mm Hg; p < 0.05 compared to baseline). Whereas close agreement between arterial and transcutaneous measurements was obtained for carbon dioxide values before hyperventilation, transcutaneous O2 consistently underestimated arterial O2. A short-term over-breathing of 3 min causes a significant posthyperventilatory hypoxemia. We hypothesize that posthyperventilatory hypoxemia is caused by hypopnea as a result of depleted CO2 body stores. Noninvasive transcutaneous blood gas measurements are not reliable for monitoring blood gas changes during and after hyperventilation, most probably because of the slow response time of the electrodes and the reflex vasoconstriction of the skin vessels.


CYP2C9 and VKORC1 polymorphisms are differently distributed in the Brazilian population according to self-declared ethnicity or genetic ancestry.
Warfarin-dosing pharmacogenetic algorithms have presented different performances across ethnicities, and the impact in admixed populations is not fully known. To evaluate the CYP2C9 and VKORC1 polymorphisms and warfarin-predicted metabolic phenotypes according to both self-declared ethnicity and genetic ancestry in a Brazilian general population plus Amerindian groups. Two hundred twenty-two Amerindians (Tupinikin and Guarani) were enrolled and 1038 individuals from the Brazilian general population who were self-declared as White, Intermediate (Brown, Pardo in Portuguese), or Black. Samples of 274 Brazilian subjects from Sao Paulo were analyzed for genetic ancestry using an Affymetrix 6.0(®) genotyping platform. The CYP2C9*2 (rs1799853), CYP2C9*3 (rs1057910), and VKORC1 g.-1639G>A (rs9923231) polymorphisms were genotyped in all studied individuals. The allelic frequency for the VKORC1 polymorphism was differently distributed according to self-declared ethnicity: White (50.5%), Intermediate (46.0%), Black (39.3%), Tupinikin (40.1%), and Guarani (37.3%) (p<0.001), respectively. The frequency of intermediate plus poor metabolizers (IM+PM) was higher in White (28.3%) than in Intermediate (22.7%), Black (20.5%), Tupinikin (12.9%), and Guarani (5.3%), (p<0.001). For the samples with determined ancestry, subjects carrying the GG genotype for the VKORC1 had higher African ancestry and lower European ancestry (0.14±0.02 and 0.62±0.02) than in subjects carrying AA (0.05±0.01 and 0.73±0.03) (p=0.009 and 0.03, respectively). Subjects classified as IM+PM had lower African ancestry (0.08±0.01) than extensive metabolizers (0.12±0.01) (p=0.02). The CYP2C9 and VKORC1 polymorphisms are differently distributed according to self-declared ethnicity or genetic ancestry in the Brazilian general population plus Amerindians. This information is an initial step toward clinical pharmacogenetic implementation, and it could be very useful in strategic planning aiming at an individual therapeutic approach and an adverse drug effect profile prediction in an admixed population.


[Specific desensitization with allergen extracts absorbed on calcium phosphate (Pasteur Institute). Clinical and biological study apropos of 107 cases].
107 allergic patients (71 children and 36 adults) were desensitized with allergen extracts adsorbed on calcium phosphate. Patients were selected following their symptoms (asthma, rhinitis, juvenile bronchitis, pollinosis), skin tests (ID or Prick) and total or specific IgE levels (PRIST and RAST). A mean of 17 month treatment, usually with house dust and mite extracts, rarely with house dust extract alone and in 6 cases with a mixture of grass and cereal pollens. The major aim of this study was to test the immunotherapy efficiency and to compare the IgE level variations and the clinical results. The treatment was found very good in 62% of the cases, good in 28%, and negative in 10% of the cases. The mean total IgE level has decreased of 58%, and the specific IgE level has decreased in 77% of the patients. The number of patients with a RAST class O to house dust and mites has increased respectively of 23% and 24.4% after the treatment. Besides some very good cases where the IgE levels have dropped there are lew relations between the total or specific IgE antibodies and the clinical results. The tolerance of the hyposensitization treatment was judged excellent. In conclusion, the calcium phosphate absorbed allergen extracts are confirmed as efficient and safe in immunotherapy.


Comparative evaluation of Melissa officinalis L., Tilia europaea L., Passiflora edulis Sims. and Hypericum perforatum L. in the elevated plus maze anxiety test.
There are numerous plants that have been used for their 'tranquillising' properties in Portuguese folk medicine. This report will describe a comparative analysis of the effects of Melissa officinalis L., Tilia europaea L., Passiflora edulis Sims. and Hypericum perforatum L. on the performance of mice in the elevated plus maze, open-field, and horizontal-wire tests. We have tested lyophilised aqueous extracts with doses ranging from 5-100 mg/kg prepared according to traditional folk medicine. The results indicate that Hypericum perforatum L. and Tilia europaea L. induced significant raise in immobility time, diminution of rearing and other parameters, suggesting a clear sedative effect at doses ranging from 10-100 mg/kg. Below these doses, Tilia europaea L. did not induce any significant change in the tests mentioned, while Hypericum perforatum L. (5 mg/kg) increased the time spent in the open areas of the elevated plus maze and the percentage of unprotected head-dips and stretch-approach postures, thus indicating an anxiolytic effect. For this dose, there were no significant changes in motor activity as measured by classical parameters for the tests used. As the infused H. perforatum L. tested was devoid of hyperforin, it can be stated that the observed effects cannot be attributed to this substance.


Role of APOE and IL18RAP gene polymorphisms in cervical spondylotic myelopathy in Indian population.
Cervical spondylotic myelopathy (CSM) is a progressive degenerative spine disease. It is not clear why certain patients develop symptomatic myelopathy whereas others do not, even in the presence of radiographic features of cervical stenosis. Genetic predisposition has been suggested, supported by familial occurrence of CSM. In this study we explored the demographic and radiographic features of CSM in Indian population and studied the association between polymorphisms in interleukin18RAP and apo-lipoprotein genes in CSM. A total of 100 CSM patients and 100 healthy control subjects were included in this study. Genotyping of APOE (rs7412 and rs429358) and IL18RAP (rs1420106 and rs917997) gene polymorphisms was performed by Taqman allelic discrimination assay. Comparison of allelic frequencies, ε2 versus ε3 (OR = 4.4, 95%CI = 1.23-15.73, P = 0.002) and ε2 versus ε4 (OR = 6.67, 95%CI = 1.58-28.04, P = 0.009) showed a statistically significant association for the risk of CSM. There was no significant association between different genotypes with sex, T2 signal intensity change and Nurick grade. Only patients having multiple level cervical prolapsed intervertebral disc (PIVD) on MRI, had a higher proportion of the ε2 allele as compared to controls (p = <0.0001). No significant association was found between IL18RAP gene polymorphisms (rs1420106 and rs917997) with the risk of CSM. ε2 allele was associated with the risk of CSM in Indian population. There was no significant association between the two single nucleotide polymorphisms (SNPs) of IL18RAP gene with risk of CSM.


Development of an electrochemical immunosensor for alanine aminotransferase.
Alanine aminotransferase (ALT) has been regarded as one of the most sensitive indicators of hepatocellular damage. While ALT is widely used in the practice of medicine, few attempts have been made to develop biosensors applicable to the on-site diagnosis of liver diseases. In the hope of developing an immunosensor for measurement of ALT activity, we have generated monoclonal antibodies to human recombinant ALT and fabricated them for use in a sensor. The ALT immunosensor was composed of the followings: (1) anti-ALT antibody-immobilized outer membrane; (2) pyruvate oxidase-absorbed inner membrane; (3) a self assembled monolayer mediator-coated gold working electrode and an Ag/AgCl reference electrode. The chronoamperometric measurement of the immunosensor was performed with 40 microl of PBS containing substrates and ALT without a washing step in less than 5 min. The dynamic range of ALT immunosensor was presented as five orders of magnitude, ranging between 10 pg/ml and 1 microg/ml. The detection limit and the sensitivity were 10 pg/ml and 26.3 nA/(ng/ml), respectively. In the meantime, the enzyme sensor fabricated without anti-ALT antibody showed much poorer analytical values. The dynamic range, the detection limit, and the sensitivity were 10 ng/ml-100 microg/ml, 10 ng/ml and 11.4 nA/(ng/ml), respectively. The presented results indicated that the immunosensor system provided much better technical performance in all of the aspects evaluated than did the enzyme sensor without the immobilized-antibody.


[Determination of plasma theophylline in the newborn by high resolution gas chromatography and specific detection (author's transl)].
The authors describe a micromethod for the determination of blood concentration of theophylline in premature newborn infants. The method includes the specificity of separation in gas phase chromatography on a glass capillary column, and the sensitivity of thermo-ionic detection. After addition of isobutyl-3-methyl-1-xanthine, which constitutes an internal standard, extraction is performed in acid pH, with the mixture dichloromethane-isopropanol. The derivation consists of an N-pentyl reaction. Analysis was carried out on a glass capillary column SE-30 measuring 75 m x 0.5 mm. The technic used is simple and rapid. Its application in pediatrics has been particularly studied; the limit of quantitative detection was 0.1 mg/l. The plasma sample may be 0.05 ml. The reproducibility is about 2% in usual therapeutic doses. The specificity of the method has been widely debated, in particular the stages of extraction, derivation, separation and detection. The authors are convinced that the analyses requiring systems of specific detection, more and more widely used, require a chromatographic apparatus with a high power of resolution; this is illustrated by an example.


Postoperative physical therapy after coronary artery bypass surgery.
Coronary artery bypass surgery is frequently complicated by postoperative atelectasis. Although routinely prescribed, the efficacy of any specific chest physical therapy is not well established. We studied patients at a university center undergoing elective coronary artery bypass surgery. Based upon chest X-ray criteria at extubation, patients (n = 228) were classified as demonstrating greater or lesser degrees of atelectasis. Those with a lesser degree of atelectasis were randomized to receive either early mobilization or sustained maximal inflations (SMI). Those with greater a degree of atelectasis were separately randomized to receive either SMI or single-handed percussions (SSP). We found the extent of atelectasis at extubation did not predict the risk of developing pneumonia. Hospital stays and intensive care unit stays were similar regardless of treatment. Physical therapy costs were highest in the most labor-intensive therapy group (SSP). We conclude that postoperative respiratory dysfunction is common but does not commonly cause significant morbidity or prolong hospital stay. Adding SMI to patients with minimal atelectasis at extubation does not improve clinical outcomes. Similarly, adding SSP to patients with marked atelectasis does not improve outcomes over those obtained with SMI and early ambulation.


[Effect of calcium antagonist nimodipine and induced hypertension on cerebral vessel reactivities, cerebral blood flow, cerebral edema and infarction in cats with one hour middle-cerebral-artery occlusion].
Treatment with the calcium entry blocker nimodipine is recommended as effective therapy for cerebral ischemia due to cerebral vasospasm or cerebral thrombosis. On the other hand, treatment with induced hypertension is a widely accepted measure to reverse ischemic deficits caused by vasospasm. Thus, a combination of the two regimens--nimodipine and induced hypertension--may have real benefits for cerebral ischemia. But it is possible that the benefit of one is abolished by adverse effects of the other, or that a combination of both may not be as effective as the use of only one therapy. In order to investigate these problems, the effects of nimodipine and induced hypertension on cerebral vessel, cerebral blood flow, cerebral edema and cerebral infarction using a one hour middle-cerebral-artery occlusion model in cats. Twenty-one anesthetized cats were divided into a control group, the nimodipine-treated group, and the nimodipine-and-induced-hypertension group. There were seven cats in each group. Occlusion of the middle cerebral artery (MCA) was continued for one hour in each animal. Induced hypertension was a little higher than resting values, and it was continued for only one hour during MCA occlusion, brought on by instillation of dopamine. Cerebral pial arteries dilated much more prominently during and after the occlusion of MCA in the nimodipine-and-induced-hypertension group than other groups. Although cerebral blood flow in the nimodipine group, and the nimodipine-and-induced-hypertension group increased more in the non-ischemic hemisphere, the most remarkable increase was seen around the infarcted cortex in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)


The 5-HT6 receptor antagonist idalopirdine potentiates the effects of acetylcholinesterase inhibition on neuronal network oscillations and extracellular acetylcholine levels in the rat dorsal hippocampus.
The 5-HT6 receptor has emerged as a promising target for cognitive disorders and combining a 5-HT6 receptor antagonist with an acetylcholinesterase inhibitor (AChEI) represents a novel approach for the symptomatic treatment of Alzheimer's disease (AD). A recent phase 2 trial showed that the selective 5-HT6 receptor antagonist idalopirdine (Lu AE58054) improved cognition in patients with moderate AD on stable treatment with the AChEI donepezil. Here we investigated the effects of idalopirdine in combination with donepezil on hippocampal function using in vivo electrophysiology and microdialysis. Network oscillations in the hippocampus were recorded during electrical stimulation of the brainstem nucleus pontis oralis (nPO) in the anesthetized rat and hippocampal acetylcholine (ACh) levels were measured in the freely-moving rat. In addition, potential pharmacokinetic interactions between idalopirdine and donepezil were assessed. Idalopirdine alone did not affect hippocampal network oscillations or ACh levels. Donepezil (0.3 and 1.0 mg/kg i.v.) dose-dependently increased hippocampal theta and gamma power during nPO stimulation. Idalopirdine (2 mg/kg i.v.), administered 1 h prior to donepezil, potentiated the theta and gamma response to 0.3 mg/kg donepezil and prolonged the gamma response to 1 mg/kg donepezil. Donepezil (1.3 mg/kg s.c.) increased extracellular ACh levels in the hippocampus and this was further augmented by administration of idalopirdine (10 mg/kg p.o.) 2 h prior to donepezil. These effects could not be attributed to a pharmacokinetic interaction between the compounds. This study demonstrates that idalopirdine potentiates the effects of donepezil on two pharmacodynamic biomarkers associated with cognition, i.e. neuronal oscillations and extracellular ACh levels in the hippocampus. Such potentiation could contribute to the procognitive effects of idalopirdine observed in donepezil-treated AD patients.


Relational spirituality and depression in adolescent girls.
This study examines the possibility that relational spirituality may be inversely associated with the relatively higher rates of adolescent depression found in girls as compared with boys. Subjects were 615 adolescents, representing a diverse range of religious, ethnic, and socioeconomic backgrounds. Overall spirituality and depression were measured using The Brief-Multidimensional Measure of Religiosity/Spirituality and the Beck Depression Inventory, respectively. Overall, both level of depression and level of relational spirituality were higher in girls as compared with boys. Regression analyses conducted independently for boys and girls revealed that daily spiritual experiences, forgiveness, and religious coping were associated with less-depressive symptomatology exclusively in girls. This pattern in the findings suggests that uniquely in girls, depression may be associated with disruptions in a relational form of spirituality.