Trajectory of criterion symptoms of major depression under newly started antidepressant treatment: sleep disturbances and anergia linger on while suicidal ideas and psychomotor symptoms disappear early.

OBJECTIVE: In modern psychiatry, depression is diagnosed with the diagnostic criteria; however, the trajectory of each of the criterion symptoms is unknown. This study aims to examine this. METHODS: We made repeated assessments of the nine diagnostic criterion symptoms with the Patient Health Questionnaire-9 (PHQ-9) among 2011 participants of a 25-week pragmatic randomised controlled trial of sertraline and/or mirtazapine for hitherto untreated major depressive episodes. The changes from baseline were estimated with the mixed-effects model with repeated measures. The time to disappearance of each symptom was modeled using the Kaplan-Meier survival analysis. RESULTS: The total score on PHQ-9 was 18.5 (SD = 3.9, n = 2011) at baseline, which decreased to 15.3 (5.2, n = 2011) at week 1, to 11.5 (5.9, n = 1953) at week 3, to 7.8 (6.0, n = 1927) at week 9, and to 6.0 (5.9, n = 1910) at week 25. Suicidal ideas, psychomotor symptoms decreased rapidly, while anergia and sleep disturbance also decreased but only slowly. The survival analyses confirmed the primary analyses. CONCLUSIONS: Upon initiation of antidepressant treatment, patients with newly treated major depressive episodes can expect their suicidal ideas and psychomotor symptoms to disappear first but sleep disturbances and anergia to linger on.

Protocol registration and selective outcome reporting in recent psychiatry trials: new antidepressants and cognitive behavioural therapies.

OBJECTIVE: The selective reporting of favorable outcomes has a serious influence on our evidence base. However, this problem has not yet been systematically investigated in the field of psychiatry. Our study aimed to evaluate registration and outcome reporting in randomized controlled trials (RCTs) of standard treatments for depression: cognitive behavioural therapy (CBT) or new-generation antidepressants (ADs). METHOD: We searched for reports of RCTs examining the efficacy of CBT or AD for depression that were published between 2011 and 2013. We then compared their primary outcomes in the trial registries and those in publications. RESULTS: We identified 170 trials. Among them, 92 trials (54.1%) were registered, 43 trials (25.3%) were properly registered, and only 32 (18.8%) trials were both properly registered and reported (the primary outcomes as recorded in the registries were reported in publications). There was no statistically significant difference in the proportions of properly registered and reported trials for CBT or AD (relative risk: 0.51, 95% CI: 0.25-1.03). High impact factor journals, commercial funding, publication of protocol, and relatively large sample size were significant predictors of proper registration and reporting. CONCLUSION: The prevalence of proper registration and reporting is still very low in depression trials.

Enthusiasm for homework and improvement of psychological distress in subthreshold depression during behavior therapy: secondary analysis of data from a randomized controlled trial.

BACKGROUND: Cognitive behavioral therapy (CBT) usually involves homework, the completion of which is a known predictor of a positive outcome. The aim of the present study was to examine the session-by-session relationships between enthusiasm to complete the homework and the improvement of psychological distress in depressed people through the course of therapy. METHODS: Working people with subthreshold depression were recruited to participate in the telephone CBT (tCBT) program with demonstrated effectiveness. Their enthusiasm for homework was enhanced with motivational interviewing techniques and was measured by asking two questions: "How strongly do you feel you want to do this homework?" and "How confident do you feel you can actually accomplish this homework?" at the end of each session. The outcome was the K6 score, which was administered at the start of each session. The K6 is an index of psychological distress including depression and anxiety. We used structural equation modeling (SEM) to elucidate the relationships between enthusiasm and the K6 scores from session to session. RESULTS: The best fitting model suggested that, throughout the course of behavior therapy (BT), enthusiasm to complete the homework was negatively correlated with the K6 scores for the subsequent session, while the K6 score measured at the beginning of the session did not influence the enthusiasm to complete the homeworks assigned for that session. CONCLUSIONS: Empirical data now support the practitioners of BT when they try to enhance their patient's enthusiasm for homework regardless of the participant's distress, which then would lead to a reduction in distress in the subsequent week. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT00885014 . April 20, 2009.

Quantitative analysis of mousy off-flavour compound 2-acetyl tetrahydropyridine in wine using liquid chromatography tandem mass spectrometry interfaced with atmospheric chemical ionisation.

2-Acetyltetrahydropyridine (ACTPY), tautomers of 2-acetyl-1,4,5,6-tetrahydropyridine and 2-acetyl-3,4,5,6-tetrahydropyridine, is reported as one of the major compounds responsible for mousy off-flavour wine. A simple and rapid method for the quantitation of ACTPY in wine using HPLC-APCI-MS/MS was developed. Only filtration and basification were required for sample preparation prior to analysis. The analytical run time was approximately 17 min for one sample. Precision and accuracy tests confirmed that the method was highly reliable and robust. Limits of quantitation (LOQ) for red and white wines were estimated to be 0.23 µg L-1, which was sufficiently sensitive to allow the quantitation of ACTPY at its odour threshold level in water. The method can be implemented for routine objective screening of wines for mousy off-flavour, to determine sensory threshold levels in wine and to aid further research aiming to reduce the occurrence of this fault in wine.

Cyanogenic glucosides in grapevine: polymorphism, identification and developmental patterns.

Twelve grapevine (Vitis vinifera L.) cultivars were surveyed for 'cyanide potential' (i.e. the total cyanide measured in beta-glucosidase-treated crude, boiled tissue extract) in mature leaves. Two related cultivars (Carignan and Ruby Cabernet) had mean cyanide potential (equivalent to 110 mgHCNkg-1fr.wt) ca. 25-fold greater than that of the other 10 cultivars, and so the trait is polymorphic in the species. In boiled leaf extracts of Carignan and Ruby Cabernet, free cyanide constituted a negligible fraction of the total cyanide potential because beta-glucosidase treatment was required to liberate the major cyanide fraction - which is therefore bound in glucosylated cyanogenic compound(s) (or cyanogenic glucosides). In addition, cyanide was liberated from ground leaf tissue of Ruby Cabernet but not Sultana (a cultivar with low cyanide potential). Hence, the high cyanide potential in Ruby Cabernet leaves is coupled with endogenous beta-glucosidase(s) activity and this cultivar may be considered 'cyanogenic'. A method was developed to detect and identify cyanogenic glucosides using liquid chromatography combined with tandem mass spectrometry (LC-MS/MS). Two putative cyanogenic glucosides were found in extracts from leaves of Carignan and Ruby Cabernet and were identified as the epimers prunasin and sambunigrin. Cyanide potential measured at three times over the growing season in young and mature leaves, petioles, tendrils, flowers, berries, seeds and roots of Ruby Cabernet was substantially higher in the leaves compared with all other tissues. This characterisation of cyanogenic glucoside accumulation in grapevine provides a basis for gauging the involvement of the trait in interactions of the species with its pests and pathogens.

Ocular manifestations in patients with microscopic polyangiitis.

PURPOSE: To describe ocular manifestations in patients with microscopic polyangiitis. METHODS: Two patients with microscopic polyangiitis complained of ocular symptoms and underwent ophthalmologic examinations. RESULTS: An 83-year-old woman (Case 1) was diagnosed with microscopic polyangiitis, according to the general clinical findings and the presence of perinuclear pattern of antineutrophil cytoplasmic antibodies (P-ANCA). She had hypopyon iridocyclitis in the right eye and retinal cotton-wool spots in the left eye. The patient was treated with oral prednisolone and subconjunctival betamethasone. The hypopyon iridocyclitis and retinal cotton-wool spots responded. A 79-year-old man (Case 2) had bilateral scleritis. The diagnosis of microscopic polyangiitis was made based on general clinical findings and the presence of P-ANCA. Scleritis was reduced after corticosteroid treatment. CONCLUSIONS: Ophthalmologists should be aware that hypopyon iridocyclitis, cotton-wool spot, and scleritis could occur in patients with microscopic polyangiitis.

Status of microchimerism in recipients 15 years after living related kidney transplantation.

To study the relevance of microchimerism to the long-term outcome of renal allografting, we analyzed the frequency of microchimerism in kidney transplant recipients who had stable graft function for 15 years or longer. Among the 104 recipients who underwent kidney transplantation between 1971 and 1980, 27 renal allografts (26%) are still functioning. Among these 27 patients, 13 recipients whose donor was still alive and cooperative were investigated for the presence of microchimerism in the peripheral blood and for their immunological status. Microchimerism was tested using the polymerase chain reaction (PCR)-single-strand conformation polymorphism (SSCP) method. To test the sensitivity of PCP-SSCP, the peripheral blood obtained within 5 weeks after transplantation (four kidney transplants, three liver transplants) was also examined. Microchimerism was detectable in five patients within 5 weeks of transplantation (kidney transplantation, 3/4; liver transplantation 2/3. However, in the patients studied 15 years after transplantation, microchimerism was detected in only one recipient (1/13). In this chimeric patient, mixed lymphocyte response revealed high responsiveness against donor antigen. In contrast, some patients who did not have chimerism showed donor-specific hyporesponsiveness in mixed lymphocyte response assay and did not develop antidonor antibody, according to flow cytometric analysis. Microchimerism is an infrequent state in the long-term survivors of kidney allografting, and this state is irrelevant to donor-specific unresponsiveness.

An intrinsic DNA curvature found in the cyanobacterium Microcystis aeruginosa K-81 affects the promoter activity of rpoD1 encoding a principal sigma factor.

The rpoD1 gene in the unicellular cyanobacterium Microcystis aeruginosa K-81 encodes a principal sigma factor of RNA polymerase and is transcribed under light and dark conditions to produce multiple monocistronic transcripts. In the 5'-upstream region from rpoD1 Promoter 2, which has a sequence of Escherichia coli type, we found a sequence-directed DNA curvature with an AT-rich sequence. Insertions of 2 to 21 base pairs introduced into the curved center changed a gross geometry of the original curved DNA structure. The rpoD1 promoter activities assayed in vivo by using transcriptional lacZ fusions were correlated with the change in the gross geometry in not only a cyanobacterium but also E. coli. In addition, RNA polymerase binding to the rpoD1 promoter region and the efficiency of the mRNA synthesis from the rpoD1 Promoter 2 were also affected in vitro by the change in the geometry. These results suggest that the tertiary structure of the curved DNA is important for the rpoD1 transcription. The deletion of the center region of the curvature resulted in a considerable reduction of the transcription from Promoter 2 in the cyanobacterium. This report demonstrates that a curved DNA plays a significant role in transcription in cyanobacteria, and that this functional curvature is located in the 5'-upstream region from the rpoD gene, which encodes a principal sigma factor in eubacteria.

1147 del A mutation in the arrestin gene in Japanese patients with Oguchi disease.

We examined the sequence of the arrestin gene in two unrelated patients with Oguchi disease. A 35-year-old woman and a 72-year-old man underwent a complete ophthalmological examination, including evaluation of visual acuity and color vision, fundus examination, and electroretinography. A golden-yellow discoloration was observed in their fundi. After 30 minutes of dark adaptation, the discoloration in the fundus disappeared. A deletion of an adenine in codon 309 of exon 11 of the arrestin gene was identified in both patients. Mutations in the arrestin are common in Japanese patients with Oguchi disease.

Pseudophakic cystoid macular edema treated with high-dose intravenous methylprednisolone.

PURPOSE: To evaluate the efficacy of high-dose methylprednisolone in the treatment of pseudophakic cystoid macular edema (CME). SETTING: University-affiliated hospital. METHODS: Four patients with pseudophakic CME who reported decreased visual acuities were treated with oral prednisolone (20 mg daily for 5 days), oral acetazolamide (500 mg daily for 5 days), and topical dexamethasone 0.1% and diclofenac 0.1% (4 times a day for 14 days). The CME did not resolve. Next, they were treated with high-dose (1000 mg daily) intravenous methylprednisolone for 3 days. RESULTS: In 3 of 4 eyes, the CME resolved and visual acuity improved. CONCLUSION: High-dose methylprednisolone may be effective in the treatment of pseudophakic CME.

Accumulation of phosphatydilcholine-hydroperoxide in dialysis patients with diabetic nephropathy.

Plasma lipid peroxidation in noninsulin dependent diabetes mellitus (DM) patients were evaluated in DM patients undergoing hemodialysis (HD) by means of a chemiluminescence-HPLC for the specific determination of phosphatidylcholine hydroperoxide (PCOOH). Thirty-three uremic patients with DM nephropathy, undergoing 12 hours HD a week using polymethylmethacrylate membrane, were studied. Of them 22 DM patients on HD were divided into 2 age and sex matched groups treated and conventional group in order to clarify therapeutic effect of 500 mg alfa-tocopherol and 600 mg probucol daily. Fifty DM patients without end-stage renal disease (ESRD) who were age-, period of diabetes-, and sex-matched, were selected as positive control of the subjects. Plasma PCOOH levels were significantly elevated in both DM patients, while the plasma PCOOH in normal controls were 227.0 +/- 68.7 pmol/ml. Plasma PCOOH levels of DM patients undergoing HD were significantly higher than that of patients without ESRD (1,330.8 +/- 642.7 pmol/ml vs. 756.6 +/- 431.9 pmol/ml, p < 0.025). Partial correlation coefficient of plasma PCOOH level demonstrated PCOOH and period of HD in DM patients were highly significantly positively correlated (p < 0.01), although single session of HD was not found to produce significantly increased lipid-peroxidation. Plasma PCOOH roughly remained within similar levels as base lines by medication with anti-oxidant compared to that of conventional group. From these results we conclude that HD intensifies lipid peroxidation and such accumulation of hydroperoxide could account for accelerated progress of atherosclerosis in DM patients with renal insufficiency. It is worthwhile to try an administration of free radical scavenger in order to reduce PCOOH and slow down the progression of atherosclerotic vascular disease.

Analysis of diacetyl in wine using solid-phase microextraction combined with gas chromatography-mass spectrometry.

Analytical difficulties in the rapid and accurate determination of diacetyl (DA), an important flavor compound in wine, at low concentrations have been overcome by the use of solid-phase microextraction (SPME) with deuterated diacetyl-d(6) (d6-DA) as an internal standard followed by gas chromatography-mass spectrometry (GC-MS). The GC-MS analyses showed that the values of the ion response ratio of DA to d6-DA were consistent regardless of the conditions of SPME headspace and were not influenced by the presence of sulfur dioxide in wine. The quantitation value of DA was represented as the concentration of free plus bound with sulfur dioxide forms of DA. The detection limit of DA in wine was as low as 0.01 microg/mL with linearity through to 10 microg/mL.

Isolation and structures of oligomeric wine pigments by bisulfite-mediated ion-exchange chromatography.

Methods have been developed that are based on cation exchange chromatography in the absence and presence of excess bisulfite for the isolation of wine pigments from Australian red wine and grape marc extract. The pigments were identified using HPLC and electrospray ionization mass spectrometry. The mass spectral data indicate that these pigments are C4-substituted anthocyanins with a tetracyclic structure. The pigments form a series of closely related oligomeric pigments which include those previously described in the literature, such as pigment A and vitisin A, as well as some newly identified pigments.

Thaumatin-like proteins and chitinases, the haze-forming proteins of wine, accumulate during ripening of grape (Vitis vinifera) berries and drought stress does not affect the final levels per berry at maturity.

Thaumatin-like proteins and chitinases, which are pathogenesis-related (PR) proteins, were the major soluble protein components of grapes from five cultivars of Vitis vinifera. This dominance of PR proteins was apparent at berry softening (véraison) and then throughout berry development for the Muscat of Alexandria, Sultana, and Shiraz cultivars and in the berries of the Sauvignon Blanc and Pinot Noir cultivars examined at commercial maturity. The M(r) of the major thaumatin-like protein from Muscat of Alexandria grapes was 21 272, and those of the three major chitinases from this cultivar, ChitB, ChitC, and ChitD, were 25 588, 25 410, and 25 457, respectively. The vines in the study were irrigated and showed no obvious signs of disease. Shiraz vines that had not been irrigated throughout the season were clearly water stressed, but had levels of PR proteins in the berry similar to vines that had been fully irrigated. It appears that the production of PR proteins that cause protein instability in wines by grapes may be little influenced by environmental conditions.

Composition of grape skin proanthocyanidins at different stages of berry development.

The composition of grape (Vitis vinifera L. cv. Shiraz) skin proanthocyanidins has been determined at different stages of berry development. Beginning approximately 3 weeks after fruit set and concluding at commercial ripeness, the composition of isolated skin proanthocyanidins was determined using the following analytical techniques: elemental analysis, UV-Vis absorption spectroscopy, reversed-phase HPLC after acid-catalysis in the presence of excess phloroglucinol, gel permeation chromatography, electrospray ionization mass spectrometry (ESI-MS), and (13)C NMR. On the basis of these analyses, berry development was correlated with an increase in proanthocyanidin mean degree of polymerization, an increase in the proportion of (-)-epigallocatechin extension subunits, and increases in the level of anthocyanins associated with the proanthocyanidin fraction. Additionally, data acquired from ESI-MS of the isolates following acid-catalysis in the presence of excess phloroglucinol is consistent with pectin-bound proanthocyanidins.

Quantitative analysis of polymeric procyanidins (Tannins) from grape (Vitis vinifera) seeds by reverse phase high-performance liquid chromatography.

A reverse phase C(18) HPLC method with potential for high automated throughput has been developed for the quantitative analysis of polymeric procyanidins (tannins) in grape seed extracts. Chromatography gave rise to 13 distinct UV-absorbing peaks with good baseline separation. The UV-absorbing peak eluting last is distinct and therefore easily quantified. Biochemical analyses including ultrafiltration, protein precipitation, and Sephadex LH20 chromatography combined with electrospray mass spectrometric analyses establish that this peak predominantly contains polymeric procyanidins. The polymers, which appear to be galloylated to various degrees and seem to fragment in a characteristic manner during electrospray mass spectrometry, are well separated from catechins and procyanidin oligomers of up to 4 units. The recovery of polymeric grape seed tannins with this HPLC method was 86%, which is similar to the 89% recovery achieved with commercial quebracho tannins. The concentration of tannins in seeds from ripe Vitis vinifera cv. Shiraz grapes ranged from 1360 to 2830 mg/kg of berries.

Use of electrospray mass spectrometry for mass determination of grape (Vitis vinifera) juice pathogenesis-related proteins: a potential tool for varietal differentiation.

Methods based on liquid chromatography-mass spectrometry (LC-MS) and protein trap mass spectrometry (trap-MS) were developed to determine the complement of pathogenesis-related (PR) proteins in grape juice. Trap-MS was superior to LC-MS in terms of simplicity, rapidity, and sensitivity. Proteins with a wide range of masses (13--33 kDa) were found in the juices of 19 different varieties of grape (Vitis vinifera) and were identified as mostly PR-5 type (thaumatin-like) and PR-3 type (chitinases) proteins. Although the PR proteins in juices of grapes are highly conserved, small consistent differences in molecular masses were noted when otherwise identical proteins were compared from different varieties. These differences persisted through different harvest years and in fruits grown in different Australian locations. With the definition of four different masses for PR-5 proteins (range = 21,239--21,272 Da) and nine different masses of PR-3 proteins (range = 25,330--25,631 Da) and using statistical analysis, the methods developed could be used for varietal differentiation of grapes grown in several South Australian locations on the basis of the PR protein composition of the juice. It remains to be seen whether this technology can be extended to grapes grown worldwide and to wine and other fruit-derived products to assist with label integrity to the benefit of consumers.

Prolongation of cardiac xenograft survival by double filtration plasmapheresis and ex vivo immunoadsorption.

A double filtration plasmapheresis (DFPP) technique and ex vivo immunoadsorption were applied to remove natural antibodies and avoid hyperacute rejection in discordant xenotransplantation. A swine heart was heterotopically transplanted into a dog's neck after DFPP and ex vivo immunoadsorption using a swine spleen or liver. Mean graft survival time was prolonged to 240 +/- 141 min in the group treated by combined DFPP and splenic adsorption, and 225 +/- 62 min in the group treated by combined DFPP and hepatic adsorption, whereas it was 9 +/- 5 min in the group without any treatment (p < 0.01). Mean removal rates of IgG and IgM were 85.5% and 93.3%, respectively. Anti-swine lymphocytotoxic antibodies and hemagglutination antibodies were also effectively removed. Deposits of canine IgM and C3 on the vascular endothelium of the graft were observed on immunofluorescence, which suggested that natural antibodies in the IgM fraction played an important role in xenohyperacute rejection.

Effects of traditional Sino-Japanese herbal medicines on aqueous flare elevation after small-incision cataract surgery.

We evaluated prospectively the effects of traditional Sino-Japanese herbal medicines on elevation of aqueous flare. Fifty-four patients with age-related cataract undergoing phacoemulsification with intraocular lens implantation were studied. In the control group, 20 patients received no herbal medicine. In the treated groups, 14 patients were given Orengedoku- to (Huanglian-Jie-Du-Tang in Chinese) granules (7.5 g daily), 10 patients were given Kakkon-to (Ge-Gen-Tang in Chinese) granules (7.5 g daily), and 10 patients were given Sairei-to (Cai-Ling-Tang in Chinese) granules (9.0 g daily), for 3 days before surgery, the day of surgery, and for 7 days after surgery. Aqueous flare was measured before and after surgery. The differences in preoperative flare intensities among the four groups were not significant. In the control group, the flare was 29.4 photon counts/msec on day 1, and then gradually decreased. The flare intensities on days 1, 3, and 5 in the Orengedoku-to and Kakkon-to groups were significantly lower than in the control group. The flare intensities in the Sairei-to group were the same as those of the controls. Oral administration of Orengedoku-to and Kakkon-to decreased aqueous flare elevation after small-incision cataract surgery. Sairei-to had no effect on the elevation.

Bilateral congenital macular coloboma in a boy with Down syndrome.

PURPOSE: To describe macular coloboma in Down syndrome. METHODS: A 12-year-old boy with Down syndrome underwent ophthalmologic examination. RESULTS: The patient had a circumscribed, round defect about 1 disc diameter, with bared sclera at the base and pigment clump at the macula in both fundi. His poor visual acuity was unchanged since childhood. The results of serum IgG and IgM titers for Toxoplasma gondii were negative. CONCLUSIONS: Congenital macular coloboma associated with Down syndrome, as demonstrated in our patient, may not have occurred by chance.