Accuracy of self-report of HIV viral load among people with HIV on antiretroviral treatment.

OBJECTIVES: The aim of the study was to assess, among people living with HIV, knowledge of their latest HIV viral load (VL) and CD4 count. METHODS: Agreement between self-report and clinic record was assessed among 2771 HIV-diagnosed individuals on antiretroviral treatment (ART) in the UK Antiretrovirals, Sexual Transmission Risk and Attitudes Study (2011-2012). A confidential self-completed questionnaire collected information on demographic, socioeconomic, HIV-related and health-related factors. Participants were asked to self-report their latest VL [undetectable (≤ 50 copies/mL), detectable (> 50 copies/mL) or "don't know"] and CD4 count (< 200, 200-350, 351-500 or > 500 cells/µL, or "don't know"). Latest clinic-recorded VL and CD4 count were documented. RESULTS: Of 2678 participants on ART, 434 (16.2%) did not accurately report whether their VL was undetectable. Of 2334 participants with clinic-recorded VL ≤ 50 copies/mL, 2061 (88.3%) correctly reported undetectable VL; 49 (2.1%) reported detectable VL; 224 (9.6%) did not know their VL. Of 344 participants with clinic-recorded VL > 50 copies/mL, 183 (53.2%) correctly reported detectable VL; 76 (22.1%) reported undetectable VL; 85 (24.7%) did not know their VL. Of 2137 participants who reported undetectable VL, clinic-recorded VL was ≤ 50 copies/mL for 2061 (96.4%) and <1000 copies/mL for 2122 (99.3%). In analyses adjusted for gender/sexual orientation, ethnicity, age and time since starting ART, factors strongly associated with inaccurate self-report of VL (including "don't know") included socioeconomic disadvantage [prevalence ratio (95% CI) for "not" vs. "always" having enough money for basic needs: 2.4 (1.9, 3.1)], poor English fluency [3.5 (2.4, 5.1) vs. UK born], nondisclosure of HIV status [1.7 (1.3, 2.1)], ART nonadherence [2.1 (1.7, 2.7) for three or more missed doses vs. none in the past 2 weeks] and depressive symptoms (PHQ-9 score ≥ 10) [1.9 (1.6, 2.2)]. Overall, 612 (22.9%) of 2667 participants on ART did not accurately self-report whether or not their CD4 count was ≤ 350 cells/µL. CONCLUSIONS: There is a high level of accuracy of a self-report of undetectable VL in people on ART in the UK. Overall, accurate knowledge of personal VL level varied according to demographic, socioeconomic, HIV-related and health-related factors. Active identification of people who may benefit from increased levels of support and engagement in care is important.

Antiretroviral therapy for prevention of HIV transmission: implications for Europe.

The aim of this review is to summarise the evidence on the population-level effect of antiretroviral therapy (ART) in preventing HIV infections, and to discuss potential implications in the European context of recommending starting ART when the CD4 count is above 350 cells/mm3. The ability of ART to reduce the risk of HIV transmission has been reported in observational studies and in a randomised controlled trial (HPTN 052), in which ART initiation reduced HIV transmission by 96% within serodiscordant couples. As yet, there is no direct evidence for such an effect among men having sex with men or people who inject drugs. HPTN 052 led international organisations to develop recommendations with a higher CD4 threshold for ART initiation. However, there remains a lack of strong evidence of clinical benefit for HIV-positive individuals starting ART with CD4 count above 350 cells/mm3. The main goal of ART provision should be to increase ART coverage for all those in need, based on the current guidelines, and the offer of ART to those who wish to reduce infectivity; increased HIV testing is therefore a key requirement. Other proven prevention means such as condom use and harm reduction for people who inject drugs remain critical.

Simultaneous determination of delta(15)N and delta(18)O of N2O and delta(13)C of CH4 in nanomolar quantities from a single water sample.

We have developed a rapid, sensitive, and automated analytical system to simultaneously determine the concentrations and stable isotopic compositions (delta(15)N, delta(18)O, and delta(13)C) of nanomolar quantities of nitrous oxide (N(2)O) and methane (CH(4)) in water, by combining continuous-flow isotope-ratio mass spectrometry and a helium-sparging system to extract and purify the dissolved gases. Our system, which is composed of cold traps and a capillary gas chromatograph that use ultra-pure helium as the carrier gas, achieves complete extraction of N(2)O and CH(4) in a water sample and separation among N(2)O, CH(4), and the other component gases. The flow path following exit from the gas chromatograph was periodically changed to pass the gases through the combustion furnace to convert CH(4) and the other hydrocarbons into CO(2), or to bypass the combustion furnace for the direct introduction of eluted N(2)O into the mass spectrometer, for determining the stable isotopic compositions through monitoring the ions of m/z 44, 45, and 46 of CO(2) (+) and N(2)O(+). The analytical system can be operated automatically with sequential software programmed on a personal computer. Analytical precisions better than 0.2 per thousand and 0.3 per thousand and better than 1.4 per thousand and 2.6 per thousand were obtained for the delta(15)N and delta(18)O of N(2)O, respectively, when more than 6.7 nmol and 0.2 nmol of N(2)O, respectively, were injected. Simultaneously, analytical precisions better than 0.07 per thousand and 2.1 per thousand were obtained for the delta(13)C of CH(4) when more than 5.5 nmol and 0.02 nmol of CH(4), respectively, were injected. In this manner, we can simultaneously determine stable isotopic compositions of a 120 mL water sample with concentrations as low as 1.7 nmol/kg for N(2)O and 0.2 nmol/kg for CH(4).

Thermochemical stabilities and structures of the cluster ions OCS+, S2+, H+(OCS), and C2H5+ with OCS molecules in the gas phase.

The gas-phase clustering reactions of OCS+, S2+, H+(OCS), and C2H5+ ions with carbonyl sulfide (OCS) molecules were studied using a pulsed electron-beam high-pressure mass spectrometer and applying density functional theory (DFT) calculations. In the cluster ions OCS+(OCS)(n) and H+(OCS)(OCS)(n), a moderately strong, here referred to as "semi-covalent", bond was formed with n = 1. However, the nature of bonding changed from semi-covalent to electrostatic with n = 1 --> 2. The bond energy of S2(+)(OCS) was determined experimentally to be 12.9 +/- 1 kcal/mol, which is significantly smaller than that of the isovalent S2(+)(CS2) complex (30.9 +/- 1.5 kcal/mol). DFT based calculations predicted the presence of several isomeric structures for H+(OCS)(OCS)(n) complexes. The bond energies in the C2H5+(OCS)(n) clusters showed an irregular decrease for n = 1 --> 2 and 7 --> 8. The nonclassical bridge structure for the free C2H5+ isomerized to form a semi-covalent bond with one OCS ligand, [H3CCH2...SCO]+, i.e., reverted to classical structure. However, the nonclassical bridge structure of C2H5+ was preserved in the cluster ions C2H5+(OCS)(n) below 140 K attributable to the lack of thermal energy for the isomerization. DFT calculations revealed that stability orders of the geometric isomers of H+(OCS)(OCS)(n) and C2H5+(OCS)(n) changed with increasing n values.

Biological properties of griseolic acid, a cyclic AMP phosphodiesterase inhibitor with an adenine group.

Griseolic acid inhibited cAMP phosphodiesterase (PDE) at low concentrations, the I50 being of the order of 0.01-0.1 microM. Administration of griseolic acid to rats increased the cAMP level in liver and plasma several-fold. It increased glycogen degradation in mouse liver and stimulated lipolysis in isolated rat fat cells. Griseolic acid did not block the adenosine-elicited accumulation of cAMP in guinea pig brain slices. It had no effect on cAMP-dependent protein kinase from rat liver nor on the adenyl cyclase from rat brain.

Selective cytochemical demonstration of glycoconjugate-containing terminal N-acetylgalactosamine on some brain neurons.

Paraffin embedded sections of rat, mouse, dog, and human brain were stained with a battery of lectin-horseradish perioxidase conjugates to localize and characterize glycoconjugates. In the rat and mouse cerebral cortex, a subpopulation of nonpyramidal neurons stained selectively with three lectins with specific affinity for terminal N-acetylgalactosamine (GalNAc). These and only these lectins stained the surface of the cell body, dendritic shafts, and proximal parts of the dendritic arborization. Most reactive, nonpyramidal neurons revealed a multipolar dendritic pattern, but some possibly belonged to the bitufted and bipolar types of neuron. The GalNAc-containing neurons appeared widely distributed in layers II-VI with relatively greater abundance in layers IV and V. In the cortex of rats and mice the stained neurons occurred in moderate numbers in the frontal, frontoparietal, striate, retrosplenial, and entorhinal regions, but were less numerous in the hippocampal gyrus, dentate gyrus, and olfactory area. Other neurons in the basal ganglia and brain stem stained weakly for GalNAc. Examination of the frontal cortex of human and canine brains showed a similar distribution of nonpyramidal neurons with affinity for GalNAc-binding lectins. At high magnification, the surface staining of neurons in the cerebral cortex, deep cerebellar nucleus, and other sites appeared periodic rather than continuous. The periodic character of the neuronal surface staining suggested a location for the reactive glycoconjugate in or between the synapses. The GalNAc-containing glycoconjugate occurred in a selected cell type, failed to bind the other lectin conjugates, and differed from biochemically detected glycoconjugates. It is, therefore, considered a newly recognized entity of possible physiologic significance for a population of cortical neurons.

Thymidylate synthase (TS) and ribonucleotide reductase (RNR) may be involved in acquired resistance to 5-fluorouracil (5-FU) in human cancer xenografts in vivo.

A human tumour sub-line resistant to 5-fluorouracil (5-FU) was established by once a day and every 5, with at least 50 administrations of 5-FU to KM12C human colorectal xenografts in nude mice. KM12C tumours treated with 5-FU showed less sensitivity to 5-FU with an inhibition rate (IR) of 7.9%, while non-treated tumours were highly sensitive to 5-FU with an IR of 81.8%. To clarify the mechanism of 5-FU-resistance, the activities of various enzymes and gene expressions involved in the metabolism of 5-FU in both parental and 5-FU-treated KM12C tumours were measured. A 2- to 3-fold increase in thymidylate synthase (TS) activity and 4- to 5-fold decrease in ribonucleotide reductase (RNR) activity were observed in 5-FU-resistant KM12C tumours, while the activities of orotate phosphoribosyltransferase (OPRT) thymidine and uridine phosphorylases (TP,UP) and thymidine kinase (TK) were not markedly changed as a consequence of repeated treatment of KM12C tumours with 5-FU. The expression of TS mRNA was also amplified in accordance with the increased TS activity in a 5-FU-treated tumour sub-line (KM12C/5-FU) compared with that in parental tumours, but changed expressions of both RNR-R1 and RNA-R2 mRNA could not be detected in the 5-FU-resistant tumour sub-line compared with the parental tumours, suggesting possible post-transcriptional regulation of RNR. Moreover, RNR, in addition to TS and OPRT, seemed to be related to the inherent insensitivity to 5-FU in human cancer xenografts. From these results, it may be concluded that RNR activity is one of the acquired or inherent resistant factors, including TS, to 5-FU in human cancer xenografts in vivo.

A case of pulmonary arteriovenous malformation in a patient with brain abscess successfully treated with video-assisted thoracoscopic resection.

A 45-year-old women was admitted to the hospital with a brain abscess due to asymptomatic pulmonary arteriovenous malformation (PAVM). The brain abscess was removed by craniotomy and excision following antibiotic therapy. The stapled wedge excision of the lung with the PAVM was successful under video-assisted thoracoscopic surgery.

An approach to a basilar aneurysm above the bifurcation of the internal carotid artery. Case report.

The authors report a case of a basilar artery aneurysm approached by the transsylvian route; the aneurysm was successfully clipped through the space distal to the carotid bifurcation and between the frontal and temporal lobes. This approach is useful when the internal carotid artery is short, sclerotic, and difficult to mobilize. Special care should be taken when retracting perforating arteries and the posterior communicating artery.

Fenestrated clips for unusual aneurysms of the carotid artery.

Twenty-four different kinds of fenestrated clips are introduced for the obliteration of unusual aneurysms. The clips were used for eight aneurysms of the internal carotid artery and 10 aneurysms of the vertebral artery. All but one of the aneurysms were successfully obliterated. Recommendations are made concerning the actual use of the clips.

Aneurysms protruding from the dorsal wall of the internal carotid artery.

Saccular aneurysms arising at locations other than at arterial divisions are extremely rare. The authors describe eight such aneurysms that protruded from the dorsal wall of the internal carotid artery (ICA) and were unrelated to any arterial junction. Radical surgery was performed in all eight cases. The aneurysms were saccular with a fragile wide or semifusiform neck. Intraoperative rupture occurred in three cases. From this experience, it is emphasized that these unusual protruding aneurysms of the dorsal ICA should be clipped with the clip blade parallel to the parent artery. In addition to clipping, complete wrapping with fascia or Bemsheet (cellulose fabric) is often advisable to prevent slippage of clips or postoperative rupture of residual aneurysm.

Noninvasive cerebral optical spectroscopy: depth-resolved measurements of cerebral haemodynamics using indocyanine green.

To investigate the feasibility of a newly developed, near-infrared optical spectroscopy device, we analysed measurements of the infrared tracer indocyanine green (ICG) using sensors with a single near infrared light source and multiple light detectors. Two ml of ICG dye, 1.0 mg ml-1 in concentration, were injected into the internal carotid artery during cerebral angiography in 14 adult patients. The resultant washout curves were measured bilaterally using sensors with 4 detectors spaced at 10, 20, 30 and 40 mm from the infrared light source on the right side, and 15, 25, 35 and 45 mm from the source for the left side, respectively. Washout curves were analysed to determine the relative amplitude of the ICG absorption signal and deduce each detector's penetration distance. When ICG was injected into the internal carotid artery, relative absorption increased with detector distance from the light source. No substantial difference in attenuation was observed in any of the detectors during external carotid injection of ICG. The resultant information related depth of penetration of the light with source-detector separation distances. The feasibility of the system for measuring cerebral oxygen saturation and haemodynamics noninvasively or monitoring at bedside is discussed.

Kinetic analysis of enantiomers of threo-methylphenidate and its metabolite in two healthy subjects after oral administration as determined by a gas chromatographic-mass spectrometric method.

A gas chromatographic-mass spectrometric method was developed for the stereoselective quantification of threo-methylphenidate (MPD) and its metabolite, ritalinic acid (RA), in plasma or urine. The plasma concentrations of (+)-MPD after oral administration of two 10-mg conventional tablets containing racemic MPD.HCl or of 20-mg of racemic MPD.HCl crystals to two healthy subjects were much higher than those of the (-)-isomer. The plasma concentrations of the metabolite, (-)-RA, were higher than that of the (+)-isomer during the first 4 h after administration of racemic MPD.HCl in both tablet and crystal forms. Although in urine both (+)- and (-)-RA were largely excreted in 48 h (37 and 40% of the dose, respectively), the percentage excretion of (-)-RA during the first 3-4 h was approximately twice that of the (+)-isomer. These results suggest that one reason for the difference in the plasma levels between (+)- and (-)-MPD may be due to differences in their rates of metabolism. Pharmacokinetic parameters of (+)-MPD after administration of 10 mg of (+)-MPD.HCl crystals were almost the same as those after administration of racemic MPD.HCl crystals. The AUC infinity 0 of (-)-MPD after administration of 10 mg of (-)-MPD.HCl crystals was smaller than that after administration of racemic MPD.HCl crystals.

Griseolic acid, an inhibitor of cyclic adenosine 3',5'-monophosphate phosphodiesterase. I. Taxonomy, isolation and characterization.

Griseolic acid, a potent inhibitor of cyclic adenosine 3',5'-monophosphate (cyclic AMP) phosphodiesterase (EC 3.1.4.17) was isolated from the cultured broth of Streptomyces griseoaurantiacus SANK 63479. Griseolic acid has an adenine moiety and two carboxyl groups and possesses the molecular formula C14H13N5O8. Griseolic acid inhibited cyclic AMP phosphodiesterase competitively with regard to cyclic AMP, the substrate and the resulting Ki value was 0.26 microM. Griseolic acid showed the most potent inhibitory effect on rat aorta cyclic AMP phosphodiesterase among the enzymes of several rat organs tested. The plasma level of cyclic AMP was increased when griseolic acid was subcutaneously injected rats.

Terferol, an inhibitor of cyclic adenosine 3',5'-monophosphate phosphodiesterase. I. Isolation and characterization.

Terferol, a new inhibitor of cyclic adenosine 3',5'-monophosphate phosphodiesterase (EC 3.1.4.17, cAMP-PDE), was isolated from the cultured broth of Streptomyces showdoensis SANK 65080. It was found to have the molecular formula C19H16O3 and to possess inhibitory activity not only against cAMP-PDE but also against cyclic guanosine 3',5'-monophosphate phosphodiesterase (cGMP-PDE) from various rat tissues. The terferol concentration required for 50% inhibition of cAMP-PDE was 0.82 microM.

Griseolic acid, an inhibitor of cyclic adenosine 3',5'-monophosphate phosphodiesterase. II. The structure of griseolic acid.

Griseolic acid, a potent inhibitor of cyclic adenosine 3',5'-monophosphate phosphodiesterase, was isolated from the fermentation broth of Streptomyces griseoaurantiacus SANK 63479. Treatment of griseolic acid with HCl-MeOH gave adenine and pseudo-sugar. The structure of griseolic acid, adenine nucleoside type structure, was elucidated by chemical degradation and X-ray analysis, and was shown to be structure 1.

Terferol, an inhibitor of cyclic adenosine 3',5'-monophosphate phosphodiesterase. II. Structural elucidation.

Streptomyces showdoensis SANK 65080 produced terferol, an inhibitor of cyclic adenosine 3',5'-monophosphate phosphodiesterase (cAMP-PDE). NMR spectrometry and X-ray analysis were used to determine the structure of the compound, a new member of the terphenyl family.

Diploic meningioma of the orbital roof.

A case of ectopic meningioma, which was confined in the diploic space of the orbital roof, is reported. Histologically, paranasal sinus mucosa was found in the tumor specimen without sharp demarcation. Nomenclature and histogenesis of this type of meningioma are discussed.

Allergens of the house dust mite, Dermatophagoides pteronyssinus, in patients with mite allergic rhinitis: a clinical investigation by intracutaneous skin tests and nasal provocation tests.

To determine the allergens of mite allergic rhinitis, we studied 31 patients with mite allergic rhinitis by skin tests and nasal provocation tests (15 for skin and 16 for nasal tests) using 6 fractions of Dermatophagoides pteronyssinus (Dp) extract differing in molecular weights (15, 25, 32, 53, 95 and 190 kDMW). In skin testing, patients showed intense positive reactions to the fractions of 15, 25, 32, 95 and 190 kDMW, among which the most patients showed positive reactions to the fractions of 15 and 25 kDMW. Significant differences were found in patients' positive reactivity among each fraction and between low (15 and 25 kD) and high (95 and 190 kD) molecular weight fractions as well. In nasal provocation tests, patients showed intense positive reactions to the fractions of 15, 32, 53 and 95 kDMW, especially to the fractions of 15 and 95 kDMW. Furthermore, the insidence of positive reactions to the 15 kDMW fraction was significantly higher than that to any other fraction in the skin tests (P < 0.05). From these results, the low molecular weight fraction, 15 kDMW, is considered to be the main allergen of this mite and the high molecular weight fractions, 95 and 190 kDMW, may also be considered to be allergens of this mite.

Major basic protein, eosinophil cationic protein, and arylsulfatase in nasal secretions of patients with Japanese cedar pollinosis.

In 15 patients with Japanese cedar pollinosis and 10 healthy control subjects, levels of major basic protein (MBP), eosinophil cationic protein (ECP), and arylsulfatase B (As) in the nasal secretions were examined before and after challenge with Japanese cedar pollen extract. The MBP and ECP levels in the patients were significantly higher 30 min after challenge than those before challenge (P < 0.005). MBP and ECP levels after challenge were significantly higher in the nasal secretions of patients than in the controls (MBP: P < 0.01, ECP: P < 0.05). The level of As after challenge was significantly higher in the nasal secretions of patients than in the controls. These results suggest that eosinophils activate or modify the immediate, nasal allergic reaction and have a role in regulating immunological responses.