Peripheral fundus findings in X-linked retinoschisis

BACKGROUND/AIMS: Vitreous haemorrhage (VH) and retinal detachment (RD) cause a precipitous decline in vision in a subset of patients with X-linked retinoschisis (XLRS), an otherwise a slowly progressive condition. This study aims to report the frequency of macular and peripheral retinal findings in a large cohort of patients with XLRS and to determine whether peripheral retinal findings are associated with VH and RD. METHODS: A retrospective observational case series was performed in 65 patients with XLRS with a pathogenic variant in retinoschisin 1. Chart review included examination notes, fundus photographs and optical coherence tomography (OCT). Fisher exact tests and univariable logistic regression analysis were used to determine the association between peripheral retinal findings (including retinoschisis, metallic sheen, vascular sheathing, pigmentary changes, white spiculations and vitreous veils) and complications (including VH and RD). RESULTS: Seven eyes (8%) showed normal macular structure on OCT. Peripheral retinoschisis was significantly associated with both VH and RD. Out of 10 eyes with complications, 9 (90%) had peripheral retinoschisis, compared with 33 out of 116 eyes (28%) without complications (p=0.0014). In addition, each additional peripheral finding increased the odds of RD by a factor of 4.06 (95% CI 1.58 to 10.39, p=0.028). There were no complications in the 28 eyes with a normal periphery (p=0.84) or in the 35 eyes with metallic sheen (p=0.42). CONCLUSION: The data suggest that patients with peripheral retinoschisis are at increased risk for VH and RD. Furthermore, patients with additional peripheral retinal findings together with peripheral schisis may carry additional risk for RD

A Carcinogenic Agent Elaborated by Liver Cells from Lymphosarcoma-Bearing Mice

Liver cells from lymphosarcoma-bearing DBA/1J mice were shown, by parabiotic culture with normal liver cells from isologous mice, to elaborate an agent which could pass a 25 mu filter and transform the normal cells to a malignant state

Role of osmolality in blood pressure stability after dialysis and ultrafiltration

Role of osmolality in blood pressure stability after dialysis and ultrafiltration. To clarify the mechanisms involved in the stability of blood pressure during ultrafiltration (UF) alone versus regular dialysis, this study systematically examined the importance of changes in serum potassium, osmolality, and plasma norepinephrine during several dialysis maneuvers. Six stable, normotensive chronic dialysis patients were subjected to a uniform 2 to 3% decrease in body weight during the 2 hours of each dialysis maneuver. Supine to upright mean blood pressure (MBP) decreased (90 to 75 mm Hg, P < 0.05), and three patients became symptomatic after weight loss during regular dialysis, but orthostatic blood pressure was stable (89 to 86 mm Hg, NS) and the patients were asymptomatic after UF and weight loss. Isokalemic regular dialysis did not afford hemodynamic stability, as orthostatic MBP declined (85 to 56 mm Hg, P < 0.02), and four of the patients again were symptomatic after standing. A continuous hypertonic mannitol (25%) infusion during the 2-hour dialysis, however, kept osmolality from decreasing and was associated with a stable orthostatic MBP (89 to 83 mm Hg, NS). A continuous infusion of isotonic mannitol (5%) given in a volume five times that of the hypertonic mannitol failed to prevent orthostatic hypotension (89 to 60 mm Hg, P < 0.005). Plasma norepinephrine concentrations were high in these patients and increased only modestly after weight loss. These results implicate constant plasma osmolality as a critical protective factor of blood pressure during UF and further demonstrate that changes in blood pressure may be dissociated from changes in both serum potassium and plasma norepinephrine concentration.Rôle de l'osmolalité dans la stabilité de la pression artérielle après dialyse et ultrafiltration. Afin de clarifier les mécanismes impliqués dans la stabilité de la pression artérielle au cours de l'ultrafiltration (UF) seule par comparaison avec la dialyse habituelle ce travail évalue systématiquement l'importance des modifications de la kaliémie, de l'osmolalité et de la norépinéphrine plasmatique au cours de plusieurs tactiques de dialyse. Six sujets stables, normotendus, en hémodialyse chronique ont subi une diminution de poids corporel de 2 à 3% au cours des 2 heures de chaque tactique de dialyse. La pression artérielle moyenne a diminué de la position couchée à la position debout (de 90 à 75 mm Hg, P < 0,05) et trois patients sont devenus symptomatiques après la perte de poids au cours de la dialyse habituelle. Par contre la pression artérielle orthostatique a été stable (89 à 86 mm Hg, NS) et les malades ont été asymptomatiques après UF. La dialyse habituelle isokaliémique n'a pas déterminé de stabilité hémodynamique, la pression artérielle moyenne orthostatique a diminué (85 à 56 mm Hg, P < 0,02) et quatre malades ont été à nouveau symptomatiques quand ils se sont levés. Cependant quand une perfusion continue de mannitol hypertonique (25%) pendant les deux heures de la dialyse a empêché la baisse de l'osmolalité la pression artérielle moyenne orthostatique a été stable (89 à 83 mm Hg, NS). Une perfusion continue de mannitol isotonique (5%) apportant un volume cinq fois celui du mannitol hypertonique n'a pas empêché l'hypotention orthostatique (89 à 60 mm Hg, P < 0,005). Les concentrations plasmatiques de norépinéphrine étaient élevées chez ces malades et n'ont que peu augmenté après la perte de poids. Ces résultats impliquent qu'une osmolalité plasmatique constante est un facteur protecteur critique pour la pression artérielle au cours de UF et ils démontrent, de plus, que les modifications de la pression artérielle peuvent être dissociées des modifications du potassium plasmatique et de la concentration de norépinéphrine

Post-treatment Effects of Erythropoietin and Nordihydroguaiaretic Acid on Recovery from Cisplatin-induced Acute Renal Failure in the Rat

5-Lipoxygenase inhibitor and human recombinant erythropoietin might accelerate renal recovery in cisplatin-induced acute renal failure rats. Male Sprague-Dawley rats were randomized into four groups: 1) normal controls; 2) Cisplatin group-cisplatin induced acute renal failure (ARF) plus vehicle treatment; 3) Cisplatin+nordihydroguaiaretic acid (NDGA) group-cisplatin induced ARF plus 5-lipoxygenase inhibitor treatment; 4) Cisplatin+erythropoietin (EPO) group-cisplatin induced ARF plus erythropoietin treatment. On day 10 (after 7 daily injections of NDGA or EPO), urea nitrogen and serum Cr concentrations were significantly lower in the Cisplatin+NDGA and Cisplatin+EPO groups than in the Cisplatin group, and 24 hr urine Cr clearances were significantly higher in the Cisplatin+EPO group than in the Cisplatin group. Semi-quantitative assessments of histological lesions did not produce any significant differences between the three treatment groups. Numbers of PCNA(+) cells were significantly higher in Cisplatin, Cisplatin+NDGA, and Cisplatin+EPO groups than in normal controls. Those PCNA(+) cells were significantly increased in Cisplatin+NDGA group. These results suggest that EPO and also NDGA accelerate renal function recovery by stimulating tubular epithelial cell regeneration

Comparative effectiveness of TNF inhibitor vs IL-6 receptor inhibitor as monotherapy or combination therapy with methotrexate in biologic-experienced patients with rheumatoid arthritis: An analysis from the CorEvitas RA Registry

Objective Randomized controlled trials (RCTs) in biologic-naïve rheumatoid arthritis (RA) patients with high disease activity and inadequate response/intolerance to methotrexate have shown interleukin-6 (IL-6) receptor inhibitors (IL-6Ri) to be superior to tumor necrosis factor inhibitors (TNFi) as monotherapy. This observational study aimed to compare the effectiveness of TNFi vs IL-6Ri as mono- or combination therapy in biologic/targeted synthetic (b/ts) -experienced RA patients with moderate/high disease activity. Methods Eligible b/ts-experienced patients from the CorEvitas RA registry were categorized as TNFi and IL-6Ri initiators, with subgroups initiating as mono- or combination therapy. Mixed-effects regression models evaluated the impact of treatment on Clinical Disease Activity Index (CDAI), patient-reported outcomes, and disproportionate pain (DP). Unadjusted and covariate-adjusted effects were reported. Results Patients initiating IL-6Ri (n = 286) vs TNFi monotherapy (n = 737) were older, had a longer RA history and higher baseline CDAI, and were more likely to initiate as third-line therapy; IL-6Ri (n = 401) vs TNFi (n = 1315) combination therapy initiators had higher baseline CDAI and were more likely to initiate as third-line therapy. No significant differences were noted in the outcomes between TNFi and IL-6Ri initiators (as mono- or combination therapy). Conclusion This observational study showed no significant differences in outcomes among b/ts-experienced TNFi vs IL-6Ri initiators, as either mono- or combination therapy. These findings were in contrast with the previous RCTs in biologic-naïve patients and could be explained by the differences in the patient characteristics included in this study. Further studies are needed to help understand the reasons for this discrepancy in the real-world b/ts-experienced population

Self-Regulation Therapy to Reproduce Drug Effects: A Suggestion Technique to Change Personality and the DRD3 Gene Expression

This study proposes a strategy, based on self-regulation therapy, to change personality and its biological substrate, the DRD3 gene expression. It has been demonstrated that acute doses of stimulating drugs, like methylphenidate, are able to change personality and the expression of certain genes in the short term. On the other hand, self-regulation therapy has been proven to reproduce the effects of drugs. Thus, it is feasible to hope that self-regulation therapy is equally effective as methylphenidate in changing personality and the gene expression. This is a preliminary study with a single-case experimental design with replication in which 2 subjects participated. The results and potential implications for research and psychotherapy are discussed.Amigó Borrás, S.; Caselles Moncho, A.; Micó Ruiz, JC. (2013). Self-Regulation Therapy to Reproduce Drug Effects: A Suggestion Technique to Change Personality and the DRD3 Gene Expression. International Journal of Clinical and Experimental Hypnosis. 61(3):282-304. doi:10.1080/00207144.2013.784094S282304613Accili, D., Fishburn, C. S., Drago, J., Steiner, H., Lachowicz, J. E., Park, B. H., … Fuchs, S. (1996). A targeted mutation of the D3 dopamine receptor gene is associated with hyperactivity in mice. Proceedings of the National Academy of Sciences, 93(5), 1945-1949. doi:10.1073/pnas.93.5.1945Amigó, S., Caselles, A., & Micó, J. C. (2008). A dynamic extraversion model. The brain’s response to a single dose of a stimulant drug. British Journal of Mathematical and Statistical Psychology, 61(1), 211-231. doi:10.1348/000711007x185514Amigó, S., Caselles, A., & Micó, J. C. (2010). General Factor of Personality Questionnaire (GFPQ): Only one Factor to Understand Personality? The Spanish journal of psychology, 13(1), 5-17. doi:10.1017/s1138741600003644Barbanti, P., Bronzetti, E., Ricci, A., Cerbo, R., Fabbrini, G., Buzzi, M. G., … Lenzi, G. L. (1996). Increased density of dopamine D5 receptor in peripheral blood lymphocytes of migraineurs: a marker for migraine? Neuroscience Letters, 207(2), 73-76. doi:10.1016/0304-3940(96)12491-5Barbanti, P., Fabbrini, G., Ricci, A., Bruno, G., Cerbo, R., Bronzetti, E., … Luigi Lenzi, G. (2000). Reduced density of dopamine D2-like receptors on peripheral blood lymphocytes in Alzheimer’s disease. Mechanisms of Ageing and Development, 120(1-3), 65-75. doi:10.1016/s0047-6374(00)00183-4Barbanti, P., Fabbrini, G., Ricci, A., Pascali, M. P., Bronzetti, E., Amenta, F., … Cerbo, R. (2000). Migraine Patients Show an Increased Density of Dopamine D3 and D4 Receptors on Lymphocytes. Cephalalgia, 20(1), 15-19. doi:10.1046/j.1468-2982.2000.00001.xBarr, G. A., Sharpless, N. S., Cooper, S., Schiff, S. R., Paredes, W., & Bridger, W. H. (1983). Classical conditioning, decay and extinction of cocaine-induced hyperactivity and stereotypy. Life Sciences, 33(14), 1341-1351. doi:10.1016/0024-3205(83)90817-2Baumann, F. (1970). Hypnosis and the Adolescent Drug Abuser. American Journal of Clinical Hypnosis, 13(1), 17-21. doi:10.1080/00029157.1970.10402074Bayot, A., Capafons, A., & Cardeña, E. (1997). Emotional Self-Regulation Therapy: A New and Efficacious Treatment for Smoking. American Journal of Clinical Hypnosis, 40(2), 146-156. doi:10.1080/00029157.1997.10403418Berke, J. D., Paletzki, R. F., Aronson, G. J., Hyman, S. E., & Gerfen, C. R. (1998). A Complex Program of Striatal Gene Expression Induced by Dopaminergic Stimulation. The Journal of Neuroscience, 18(14), 5301-5310. doi:10.1523/jneurosci.18-14-05301.1998Blachly, P. H. (1971). An «Electric Needle» for Aversive Conditioning of the Needle Ritual. International Journal of the Addictions, 6(2), 327-328. doi:10.3109/10826087109057791Brown, E., Robertson, G., & Fibiger, H. (1992). Evidence for conditional neuronal activation following exposure to a cocaine-paired environment: role of forebrain limbic structures. The Journal of Neuroscience, 12(10), 4112-4121. doi:10.1523/jneurosci.12-10-04112.1992Caine, S., & Koob, G. (1993). Modulation of cocaine self-administration in the rat through D-3 dopamine receptors. Science, 260(5115), 1814-1816. doi:10.1126/science.8099761Capafons, A., & Amigoó, S. (1995). Emotional Self-Regulation Therapy for Smoking Reduction: Description and Initial Empirical Data. International Journal of Clinical and Experimental Hypnosis, 43(1), 7-19. doi:10.1080/00207149508409372Caselles, A., Micó, J. C., & Amigó, S. (2010). Cocaine addiction and personality: A mathematical model. British Journal of Mathematical and Statistical Psychology, 63(2), 449-480. doi:10.1348/000711009x470768Caselles, A., Micó, J. C., & Amigó, S. (2011). Dynamics of the General Factor of Personality in Response to a Single Dose of Caffeine. The Spanish journal of psychology, 14(2), 675-692. doi:10.5209/rev_sjop.2011.v14.n2.16Comings, D., Gade-Andavolu, R., Gonzalez, N., Wu, S., Muhleman, D., Blake, H., … MacMurray, J. (2001). A multivariate analysis of 59 candidate genes in personality traits: the temperament and character inventory. Clinical Genetics, 58(5), 375-385. doi:10.1034/j.1399-0004.2000.580508.xCzermak, C., Lehofer, M., Renger, H., Wagner, E. M., Lemonis, L., Rohrhofer, A., … Liebmann, P. M. (2004). Dopamine receptor D3 mRNA expression in human lymphocytes is negatively correlated with the personality trait of persistence. Journal of Neuroimmunology, 150(1-2), 145-149. doi:10.1016/j.jneuroim.2004.01.009Daly, S. A., & Waddington, J. L. (1993). Behavioural effects of the putative D-3 dopamine receptor agonist 7-OH-DPAT in relation to other «D-2-like» agonists. Neuropharmacology, 32(5), 509-510. doi:10.1016/0028-3908(93)90177-5Gilbert, D. G., & Hagen, R. L. (1985). Electrodermal responses to movie stressors: Nicotine × extraversion interactions. Personality and Individual Differences, 6(5), 573-578. doi:10.1016/0191-8869(85)90006-6Gilbert, D. B., Millar, J., & Cooper, S. J. (1995). The putative dopamine D3 agonist, 7-OH-DPAT, reduces dopamine release in the nucleus accumbens and electrical self-stimulation to the ventral tegmentum. Brain Research, 681(1-2), 1-7. doi:10.1016/0006-8993(95)00247-nHastings, A. (2006). An Extended Nondrug MDMA-Like Experience Evoked Through Posthypnotic Suggestion. Journal of Psychoactive Drugs, 38(3), 273-283. doi:10.1080/02791072.2006.10399853Ilani, T., Ben-Shachar, D., Strous, R. D., Mazor, M., Sheinkman, A., Kotler, M., & Fuchs, S. (2001). A peripheral marker for schizophrenia: Increased levels of D3 dopamine receptor mRNA in blood lymphocytes. Proceedings of the National Academy of Sciences, 98(2), 625-628. doi:10.1073/pnas.98.2.625Kollins, S. H., MacDonald, E. K., & Rush, C. R. (2001). Assessing the abuse potential of methylphenidate in nonhuman and human subjects: a review. Pharmacology Biochemistry and Behavior, 68(3), 611-627. doi:10.1016/s0091-3057(01)00464-6Lejeune, F., & Millan, M. J. (1995). Activation of dopamine D3 autoreceptors inhibits firing of ventral tegmental dopaminergic neurones in vivo. European Journal of Pharmacology, 275(3), R7-R9. doi:10.1016/0014-2999(95)00106-uLevant, B. (1998). Differential distribution of D3 dopamine receptors in the brains of several mammalian species. Brain Research, 800(2), 269-274. doi:10.1016/s0006-8993(98)00529-0LEVINE, D. G. (1974). «Needle Freaks»: Compulsive Self-Injection Drug Users. American Journal of Psychiatry, 131(3), 297-300. doi:10.1176/ajp.131.3.297LYNCH, J. J., STEIN, E. A., & FERTZIGER, A. P. (1976). AN ANALYSIS OF 70 YEARS OF MORPHINE CLASSICAL CONDITIONING. The Journal of Nervous and Mental Disease, 163(1), 47-58. doi:10.1097/00005053-197607000-00007Merchant, K. M., Figur, L. M., & Evans, D. L. (1996). Induction of c-fos mRNA in Rat Medial Prefrontal Cortex by Antipsychotic Drugs: Role of Dopamine D2 and D3 Receptors. Cerebral Cortex, 6(4), 561-570. doi:10.1093/cercor/6.4.561Muntaner, C., Cascella, N. G., Kumor, K. M., Nagoshi, C., Herning, R., & Jaffe, J. (1989). Placebo responses to cocaine administration in humans: effects of prior administrations and verbal instructions. Psychopharmacology, 99(2), 282-286. doi:10.1007/bf00442823Musek, J. (2007). A general factor of personality: Evidence for the Big One in the five-factor model. Journal of Research in Personality, 41(6), 1213-1233. doi:10.1016/j.jrp.2007.02.003Nagai, Y., Ueno, S., Saeki, Y., Soga, F., Hirano, M., & Yanagihara, T. (1996). Decrease of the D3 dopamine receptor mRNA expression in lymphocytes from patients with Parkinson’s disease. Neurology, 46(3), 791-795. doi:10.1212/wnl.46.3.791Neisewander, J. L., Baker, D. A., Fuchs, R. A., Tran-Nguyen, L. T. L., Palmer, A., & Marshall, J. F. (2000). Fos Protein Expression and Cocaine-Seeking Behavior in Rats after Exposure to a Cocaine Self-Administration Environment. The Journal of Neuroscience, 20(2), 798-805. doi:10.1523/jneurosci.20-02-00798.2000IMissbrandt, H., Ekman, A., Eriksson, E., & Heilig, M. (1995). Dopamine D3 receptor antisense influences dopamine synthesis in rat brain. NeuroReport, 6(3), 573-576. doi:10.1097/00001756-199502000-00041O’BRIEN, C. P., CHILDRESS, A. R., McLELLAN, A. T., & EHRMAN, R. (1992). Classical Conditioning in Drug-Dependent Humans. Annals of the New York Academy of Sciences, 654(1 The Neurobiol), 400-415. doi:10.1111/j.1749-6632.1992.tb25984.xO’Brien, C. P., Nace, E. P., Mintz, J., Meyers, A. L., & Ream, N. (1980). Follow-up of Vietnam veterans. I. relapse to drug use after Vietnam service. Drug and Alcohol Dependence, 5(5), 333-340. doi:10.1016/0376-8716(80)90159-3Pilla, M., Perachon, S., Sautel, F., Garrido, F., Mann, A., Wermuth, C. G., … Sokoloff, P. (1999). Selective inhibition of cocaine-seeking behaviour by a partial dopamine D3 receptor agonist. Nature, 400(6742), 371-375. doi:10.1038/22560Post, R. M., Lockfeld, A., Squillace, K. M., & Contel, N. R. (1981). Drug-environment interaction: Context dependency of cocaine-induced behavioral sensitization. Life Sciences, 28(7), 755-760. doi:10.1016/0024-3205(81)90157-0Ricci, A., Bronzetti, E., Mignini, F., Tayebati, S. K., Zaccheo, D., & Amenta, F. (1999). Dopamine D1-like receptor subtypes in human peripheral blood lymphocytes. Journal of Neuroimmunology, 96(2), 234-240. doi:10.1016/s0165-5728(99)00042-9Schiltz, C. A., Kelley, A. E., & Landry, C. F. (2005). Contextual cues associated with nicotine administration increasearcmRNA expression in corticolimbic areas of the rat brain. European Journal of Neuroscience, 21(6), 1703-1711. doi:10.1111/j.1460-9568.2005.04001.xSchutte, N. S., Malouff, J. M., Segrera, E., Wolf, A., & Rodgers, L. (2003). States reflecting the Big Five dimensions. Personality and Individual Differences, 34(4), 591-603. doi:10.1016/s0191-8869(02)00031-4Smith, B. D., Rockwell-Tischer, S., & Davidson, R. (1986). Extraversion and arousal: Effects of attentional conditions on electrodermal activity. Personality and Individual Differences, 7(3), 293-303. doi:10.1016/0191-8869(86)90004-8Stewart, J., de Wit, H., & Eikelboom, R. (1984). Role of unconditioned and conditioned drug effects in the self-administration of opiates and stimulants. Psychological Review, 91(2), 251-268. doi:10.1037/0033-295x.91.2.251Strange, P. G. (1993). New insights into dopamine receptors in the central nervous system. Neurochemistry International, 22(3), 223-236. doi:10.1016/0197-0186(93)90050-fSuzuki, M., Hurd, Y. L., Sokoloff, P., Schwartz, J.-C., & Sedvall, G. (1998). D3 dopamine receptor mRNA is widely expressed in the human brain. Brain Research, 779(1-2), 58-74. doi:10.1016/s0006-8993(97)01078-0Takahashi, N., Nagai, Y., Ueno, S., Saeki, Y., & Yanagihara, T. (1992). Human peripheral blood lymphocytes express D5 dopamine receptor gene and transcribe the two pseudogenes. FEBS Letters, 314(1), 23-25. doi:10.1016/0014-5793(92)81452-rTorres, G., & Rivier, C. (1994). Induction of c-fos in rat brain by acute cocaine and fenfluramine exposure: a comparison study. Brain Research, 647(1), 1-9. doi:10.1016/0006-8993(94)91391-9Volkow, N. D., Wang, G.-J., Fowler, J. S., Gatley, S. J., Logan, J., Ding, Y.-S., … Pappas, N. (1998). Dopamine Transporter Occupancies in the Human Brain Induced by Therapeutic Doses of Oral Methylphenidate. American Journal of Psychiatry, 155(10), 1325-1331. doi:10.1176/ajp.155.10.1325Volkow, N. D., Wang, G.-J., Fowler, J. S., Telang, F., Maynard, L., Logan, J., … Swanson, J. M. (2004). Evidence That Methylphenidate Enhances the Saliency of a Mathematical Task by Increasing Dopamine in the Human Brain. American Journal of Psychiatry, 161(7), 1173-1180. doi:10.1176/appi.ajp.161.7.1173Vorel, S. R., Ashby, C. R., Paul, M., Liu, X., Hayes, R., Hagan, J. J., … Gardner, E. L. (2002). Dopamine D3Receptor Antagonism Inhibits Cocaine-Seeking and Cocaine-Enhanced Brain Reward in Rats. The Journal of Neuroscience, 22(21), 9595-9603. doi:10.1523/jneurosci.22-21-09595.2002Yano, M., & Steiner, H. (2004). Topography of Methylphenidate (Ritalin)-Induced Gene Regulation in the Striatum: Differential Effects on c-Fos, Substance P and Opioid Peptides. Neuropsychopharmacology, 30(5), 901-915. doi:10.1038/sj.npp.130061