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Resumen: Introducción: El síndrome de pseudotumor cerebri (SPTC) en pacientes prepuberales presenta características que lo diferencian respecto a su presentación en la etapa pospuberal. Nuestro objetivo es describir las características de los pacientes diagnosticados de SPTC pediátrico en nuestro centro y compararlas en función de su estado puberal. Pacientes y métodos: Se incluyeron a los pacientes diagnosticados de SPTC en un hospital de tercer nivel entre los años 2006 y 2019 con edades comprendidas entre uno y 18 años que cumplieran los criterios diagnósticos actualizados del SPTC. Se clasificaron en función de su estado puberal y peso corporal. Posteriormente, se analizaron los datos de las punciones lumbares, estudios de neuroimagen, valoraciones oftalmológicas, así como el régimen terapéutico recibido a lo largo de su seguimiento. Resultados: Se recogieron 28 pacientes, 22 prepuberales y seis pospuberales, con edad media de 9,04 ± 2,86 años. El 83,3% de los pacientes pospuberales eran varones presentando sobrepeso/obesidad en el 66,7%. Eran varones el 27% de los pacientes prepuberales, de ellos asociaban sobrepeso el 31,8%. La sintomatología más frecuente fue cefalea (89,9%) y visión borrosa (42,9%). Todos los pacientes presentaron papiledema; un 21,4% de los casos presentaron parálisis del VI par. Se identificó un posible desencadenante en un 28,6%. El 19% presentaron recurrencia clínica, siendo todos ellos prepuberales. La resolución clínica completa se produjo en el 55,6% de los pacientes. Conclusión: Pacientes con SPTC presentan menor prevalencia de obesidad en la etapa prepuberal, junto con un mayor porcentaje de etiologías secundarias y tasa de recurrencia que los pacientes pospuberales. Abstract: Introduction: Pseudotumor cerebri (PC) in prepubertal patients displays certain characteristics that differentiate it from its presentation at the postpubertal stage. The aim of this study is to describe the characteristics of paediatric patients diagnosed with PC at our centre and to compare them according to their pubertal status. Patients and methods: We included patients aged between 1 and 18 years who were diagnosed with PC in a tertiary-level hospital between 2006 and 2019 and who met the updated diagnostic criteria for PC. They were classified according to body weight and pubertal status. Subsequently, we analysed results from lumbar punctures, neuroimaging studies, ophthalmological assessments, and treatments received during follow-up. Results: We included 28 patients, of whom 22 were of prepubertal age and 6 were of postpubertal age. The mean age (standard deviation) was 9.04 (2.86) years. Among the postpubertal patients, 83.3% were boys, 66.7% of whom presented overweight/obesity. In the group of prepubertal patients, 27% were boys, 31.8% of whom were overweight. The most frequent symptoms were headache (89.9%) and blurred vision (42.9%). All patients presented papilloedema, and 21.4% manifested sixth nerve palsy. Possible triggers were identified in 28.6% of cases. Nineteen percent of patients presented clinical recurrence, all of whom were prepubertal patients. Complete clinical resolution was achieved in 55.6% of patients. Conclusion: Prepubertal patients with PC show lower prevalence of obesity, higher prevalence of secondary aetiologies, and higher recurrence rates than postpubertal patients.

Introduction: Pseudotumor cerebri (PC) in prepubertal patients displays certain characteristics that differentiate it from its presentation at the postpubertal stage. The aim of this study is to describe the characteristics of paediatric patients diagnosed with PC at our centre and to compare them according to their pubertal status. Patients and methods: We included patients aged between 1 and 18 years who were diagnosed with PC in a tertiary-level hospital between 2006 and 2019 and who met the updated diagnostic criteria for PC. They were classified according to body weight and pubertal status. Subsequently, we analysed results from lumbar punctures, neuroimaging studies, ophthalmological assessments, and treatments received during follow-up. Results: We included 28 patients, of whom 22 were of prepubertal age and 6 were of postpubertal age. The mean age (standard deviation) was 9.04 (2.86) years. Among the postpubertal patients, 83.3% were boys, 66.7% of whom presented overweight/obesity. In the group of prepubertal patients, 27% were boys, 31.8% of whom were overweight. The most frequent symptoms were headache (89.9%) and blurred vision (42.9%). All patients presented papilloedema, and 21.4% manifested sixth nerve palsy. Possible triggers were identified in 28.6% of cases. Nineteen percent of patients presented clinical recurrence, all of whom were prepubertal patients. Complete clinical resolution was achieved in 55.6% of patients. Conclusion: Prepubertal patients with PC show lower prevalence of obesity, higher prevalence of secondary aetiologies, and higher recurrence rates than postpubertal patients. Resumen: Introducción: El Síndrome de Pseudotumor Cerebri (SPTC) en pacientes prepuberales presenta características que lo diferencian respecto a su presentación en la etapa postpuberal. Nuestro objetivo es describir las características de los pacientes diagnosticados de SPTC pediátrico en nuestro centro y compararlas en función de su estado puberal. Pacientes y métodos: Se incluyeron a los pacientes diagnosticados de SPTC en un hospital de tercer nivel entre los años 2006 y 2019 con edades comprendidas entre 1 y 18 años que cumplieran los criterios diagnósticos actualizados del SPTC. Se clasificaron en función de su estado puberal y peso corporal. Posteriormente, se analizaron los datos de las punciones lumbares, estudios de neuroimagen, valoraciones oftalmológicas, así como el régimen terapéutico recibido a lo largo de su seguimiento. Resultado: Se recogieron 28 pacientes, 22 prepuberales y 6 postpuberales, con edad media de 9,04 ± 2,86 años. El 83,3% de los pacientes postpuberales eran varones presentando sobrepeso/obesidad en el 66,7%. Eran varones el 27% de los pacientes prepuberales, de ellos asociaban sobrepeso el 31,8%. La sintomatología más frecuente fue cefalea (89,9%) y visión borrosa (42,9%). Todos los pacientes presentaron papiledema; un 21,4% de los casos presentaron parálisis del VI par. Se identificó un posible desencadenante en un 28,6%. El 19% presentaron recurrencia clínica, siendo todos ellos prepuberales. La resolución clínica completa se produjo en el 55,6% de los pacientes. Conclusión: Pacientes con SPTC presentan menor prevalencia de obesidad en la etapa prepuberal, junto con un mayor porcentaje de etiologías secundarias y tasa de recurrencia que los pacientes postpuberales.

Introducción El objetivo del estudio fue analizar las residencias ortopedia y traumatología en Argentina y determinar: 1) La proporción de mujeres; 2) Diferencias sociales y demográficas entre géneros: 3) Los factores que influyen positiva o negativamente en las mujeres al elegir ortopedia. Métodos Se realizó un estudio observacional y descriptivo en dos fases. Primera fase: se analizó la base de datos de la “Asociación Argentina de Ortopedia y Traumatología¨ durante el período 2016-2017. Segunda fase: se desarrolló una encuesta, enfocada en cuestiones demográficas, sociales y laborales, y se envió a todos los residentes de ortopedia. Resultados y conclusión Se incluyeron 933 residentes,121 (13%) eran mujeres y 812 (87%) eran hombres. Recibimos 259 (28%) respuestas de la encuesta. En las características demográficas encontramos diferencias estadísticamente significativas en términos de matrimonio o convivencia: mujeres (16%) vs hombres (42%) (p

Objectives: Pleural mesothelioma (PM) is an aggressive disease linked to asbestos exposure, presenting significant treatment challenges. The recommended approach is multimodal treatment, even if the concept of resectable PM and the superiority of one surgical technique over the other [(extended) pleurectomy decortication [(E)PD] vs extra-pleural pneumonectomy (EPP)] are matter of debates. The aim of this study is to compare the 2 techniques in terms of short- and long-term outcomes at a high-volume centre., Methods: Clinical data from PM patients who underwent radical surgery [(E)PD and EPP] between 1994 and 2022 were collected. A propensity score weighting approach was used for non-random intervention allocation. Survival distribution was estimated using Kaplan-Meier method and the association with outcomes was evaluated using a weighted Cox proportional hazard models., Results: Among 254 patients, 125 (49%) underwent EPP and 129 (51%) (E)PD. The 90-day mortality was higher in the EPP group (7.2% vs 0%; P = 0.01). No difference in 1-, 3- and 5-year survival was found: 65.8%, 26%, 17% for EPP and 75.5%, 39.7% and 21.3% for (E)PD; P = 0.39. The multivariable-weighted Cox model identified no increased risk of death [hazard ratio (HR) 1.25; P = 0.49] or recurrence (HR 1.05; P = 0.858) in the EPP group. Pre-operative total lung capacity was significantly associated with a reduced risk of death (HR 0.96; P = 0.023) and recurrence (HR 0.97; P = 0.019) at follow-up, while pre-operative disease burden to a higher risk of recurrence (HR 1.01; P = 0.02)., Conclusions: Our experience showed acceptable short- and long-term outcomes in both procedures, making EPP still an option only for carefully selected patients at high-volume centre. Surgery, although recently debated, should be performed exclusively in expert centres to minimize post-operative risks. The identification of new prognostic factors is crucial for better selecting patients who may benefit from surgery within the context of multimodal treatment., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Introduction: Recent diagnostic criteria for optic neuritis include T2-hyperintensity of the optic nerve (ON), even without associated contrast enhancement. However, isolated ON-T2-hyperintensity is a nonspecific finding found in any optic neuropathy or severe retinopathy. We applied the 2022 optic neuritis diagnostic criteria to a cohort of patients with noninflammatory optic neuropathy and ON-T2-hyperintensity in at least one eye, to assess the rate of optic neuritis misdiagnosis using these criteria., Methods: Retrospective study of consecutive patients who underwent brain/orbit MRI with/without contrast between 07/01/2019 and 06/30/2022. Patients with ON-T2-hyperintensity in at least one eye were included. The 2022 optic neuritis diagnostic criteria were applied to patients with noninflammatory optic neuropathies who had an ophthalmologic examination available for review., Results: Of 150 patients included, 85/150 had compressive optic neuropathy; 32/150 had glaucoma; 12/150 had papilledema; 8/150 had hereditary (3), radiation-induced (3), nutritional (1), traumatic (1) optic neuropathies (none fulfilled the criteria); 13/150 had ischemic optic neuropathy and 4 fulfilled the criteria as definite optic neuritis due to contrast enhancement of the ON head. Seven additional patients would have satisfied the diagnostic criteria if red flags for alternative diagnoses had been overlooked., Discussion: The application of the 2022 optic neuritis diagnostic criteria in patients with noninflammatory optic neuropathy and ON-T2-hyperintensity in at least one ON resulted in misdiagnosis of optic neuritis in only 4 patients because of ON head enhancement, all with nonarteritic anterior ischemic optic neuropathy. Neuro-ophthalmologic evaluation and exclusion of the ON head as a location in the MRI criteria would have prevented optic neuritis misdiagnosis in our study., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Background/objectives: To report a series of patients with glaucoma and optic nerve abnormalities on magnetic resonance imaging (MRI) in at least one-eye, and to determine whether these findings correlate with the severity of glaucoma., Patients and Methods: Retrospective study of all patients who underwent a brain/orbits MRI without and with contrast at our institution between 07/1/2019-6/30/2022. Patients with optic nerve T2-hyperintensity and/or MRI optic nerve atrophy in at least one-eye and a diagnosis of isolated glaucoma in at least one-eye were included. Demographic information, glaucoma clinical characteristics, glaucoma severity parameters, and MRI indication were collected., Results: Fifty-six patients (112 eyes) (age 65 years-old [range 26-88]; 70% male) had isolated bilateral glaucoma with at least one-eye MRI optic nerve abnormality. The indication for MRI was atypical/asymmetric glaucoma in 91% of patients. Of the 112 eyes, 23 had optic nerve T2-hyperintensity alone; 33 had both optic nerve T2-hyperintensity and MRI optic nerve atrophy; 34 had MRI optic nerve atrophy alone; and 22 did not have abnormal optic nerve MRI-findings. None had optic nerve enhancement. A statistically significant association between optic nerve T2-hyperintensity or MRI optic nerve atrophy and glaucoma severity parameters was found., Conclusions: Glaucoma is a clinical diagnosis and MRI brain is usually not required, except in atypical or asymmetric cases. Optic nerve T2-hyperintensity and MRI optic nerve atrophy are nonspecific MRI-findings that can be found in severe glaucomatous optic nerves and should not systematically prompt investigations for another cause of optic neuropathy., (© 2024. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Background: MRI abnormalities are common in optic neuropathies, especially on dedicated orbital imaging. In acute optic neuritis, optic nerve T2-hyperintensity associated with optic nerve contrast enhancement is the typical imaging finding. In chronic optic neuropathies, optic nerve T2-hyperintensity and atrophy are regularly seen. Isolated optic nerve T2-hyperintensity is often erroneously presumed to reflect optic neuritis, frequently prompting unnecessary investigations and neuro-ophthalmology consultations. Our goal was to determine the significance of optic nerve/chiasm T2-hyperintensity and/or atrophy on MRI., Methods: Retrospective study of consecutive patients who underwent brain/orbital MRI with/without contrast at our institution between July 1, 2019, and June 6, 2022. Patients with optic nerve/chiasm T2-hyperintensity and/or atrophy were included. Medical records were reviewed to determine the etiology of the T2-hyperintensity and/or atrophy., Results: Four hundred seventy-seven patients (698 eyes) were included [mean age 52 years (SD ±18 years); 57% women]. Of the 364 of 698 eyes with optic nerve/chiasm T2-hyperintensity without atrophy, the causes were compressive (104), inflammatory (103), multifactorial (49), glaucoma (21), normal (19), and other (68); of the 219 of 698 eyes with optic nerve/chiasm T2-hyperintensity and atrophy, the causes were compressive (57), multifactorial (40), inflammatory (38), glaucoma (33), normal (7), and other (44); of the 115 of 698 eyes with optic nerve/chiasm atrophy without T2-hyperintensity, the causes were glaucoma (34), multifactorial (21), inflammatory (13), compressive (11), normal (10), and other (26). Thirty-six eyes with optic nerve/chiasm T2-hyperintensity or atrophy did not have evidence of optic neuropathy or retinopathy on ophthalmologic examination, and 17 eyes had clinical evidence of severe retinopathy without primary optic neuropathy., Conclusions: Optic nerve T2-hyperintensity or atrophy can be found with any cause of optic neuropathy and with severe chronic retinopathy. These MRI findings should not automatically prompt optic neuritis diagnosis, workup, and treatment, and caution is advised regarding their use in the diagnostic criteria for multiple sclerosis. Cases of incidentally found MRI optic nerve T2-hyperintensity and/or atrophy without a known underlying optic neuropathy or severe retinopathy are rare. Such patients should receive an ophthalmologic examination before further investigations., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 by North American Neuro-Ophthalmology Society.)

Purpose: To compare the direct costs associated with the dexamethasone intravitreal implant (DEX-i) in treatment-naïve and previously treated eyes with diabetic macular edema (DME) in a real clinical setting., Methods: Retrospective and single-center study conducted in a real clinical scenario. Consecutive DME patients, either naïve or previously treated with vascular endothelial growth factor inhibitors (anti-VEGF), who received treatment with one or more DEX-i between May 2015 and December 2020, and who were followed-up for a minimum of 12 months, were included in the study. The cost analysis was performed from the perspective of the Andalusian Regional Healthcare Service. The primary effectiveness endpoint was the probability of achieving an improvement in best-corrected visual acuity (BCVA) ≥ 15 ETDRS letters after 1 year of treatment. The incremental cost-effectiveness ratio (ICER) of different improvements in BCVA was calculated., Results: Forty-nine eyes, twenty-eight (57.1%) eyes from the treatment-naïve group and twenty-one (42.9%) from the previously treated group, were included in the analysis. The total cost of one year of treatment was significantly lower in the treatment-naïve eyes than in the previously treated eyes [Hodges-Lehmann median difference: EUR 819.1; 95% confidence interval (CI): EUR 786.9 to EUR 1572.8; p < 0.0001]. The probability of achieving a BCVA improvement of ≥15 letters at month 12 was significantly greater in the treatment-naïve group than in the previously treated group (rate difference: 0.321; 95% CI: 0.066 to 0.709; p = 0.0272). The Cochran-Mantel-Haenszel Odds Ratio of achieving a BCVA improvement of ≥15 letters at month 12 was 3.55 (95% CI: 1.09 to 11.58; p = 0.0309). In terms of ICER, the treatment-naïve group showed cost savings of EUR 7704.2 and EUR 5994.2 for achieving an improvement in BCVA ≥ 15 letters at month 12 and at any of the measured time points, respectively., Conclusions: DEX-i was found to be more cost-effective in treatment-naïve eyes than in those previously treated with anti-VEGF. Further studies are needed to determine the most cost-effective treatment based on patient profile.

Surgery for malignant pleural mesothelioma (MPM) should be reserved only for patients who have a good performance status. Sarcopenia, a well-known predictor of poor outcomes after surgery, is still underinvestigated in MPM. The aim of this study is to evaluate the role of sarcopenia as a predictor of short-and long-term outcomes in patients surgically treated for MPM. In our analysis, we included patients treated with a cytoreductive intent in a multimodality setting, with both pre- and post-operative CT scans without contrast available. We excluded those in whom a complete macroscopic resection was not achieved. Overall, 86 patients were enrolled. Sarcopenia was assessed by measuring the mean muscular density of the bilateral paravertebral muscles (T12 level) on pre-and post-operative CTs; a threshold value of 30 Hounsfield Units (HU) was identified. Sarcopenia was found pre-operatively in 57 (66%) patients and post-operatively in 61 (74%). Post-operative sarcopenic patients had a lower 3-year overall survival (OS) than those who were non-sarcopenic (34.9% vs. 57.6% p = 0.03). Pre-operative sarcopenia was significantly associated with a higher frequency of post-operative complications (65% vs. 41%, p = 0.04). The evaluation of sarcopenia, through a non-invasive method, would help to better select patients submitted to surgery for MPM in a multimodality setting.

Background: Encouraging professional integrity is vital for providing a standard of excellence in quality medical care and education and in promoting a culture of respect and responsibility. The primary objective of this work consisted of studying the relationship of medical students to the right to patient privacy in Spain, specifically by analysing the conditions for accessing patient clinical histories (CHs)., Methods: A cross-sectional study was conducted based on a questionnaire sent by e-mail to final-year students at 41 Spanish universities. It had 14 multiple choice and closed questions framed in 3 large blocks. The first question addressed basic general knowledge issues on the right to privacy and the obligation for confidentiality. The two remaining blocks were made up of questions directed towards evaluating the frequency with which certain requirements and action steps related to students attending patients were performed and regarding the guarantees associated with accessing and handling patient CHs both on paper and in the Electronic Medical Record., Results: A total of 245 valid replies were considered. A total of 67.8 % of participants were women, with an average age of 24.05 ± 3.49 years. Up to 90.6 % were aware that confidentiality affected the data in CHs, although 43.3 % possessed non-anonymized photocopies of patient clinical reports outside the healthcare context, and only 49.8 % of the students were always adequately identified. A total of 59.2 % accessed patient CHs on some occasions by using passwords belonging to healthcare professionals, 77.2 % of them did not have the patients' express consent, and 71.9 % accessed a CH that was not anonymised., Conclusions: The role of healthcare institutions and universities is considered to be fundamental in implementing educational measures regarding the risks and ethical and legal problems arising from the use of CHs among professionals and students. A thorough study of medical ethics is needed through the analysis of clinical cases and direct exposure to situations in which the patient's confidentiality is questioned.

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system whose etiology remains unclear. It has been suggested that MS can be triggered by certain viruses; however, human immunodeficiency virus (HIV) infection is associated with reduced incidence of MS. We present the case of a young patient diagnosed with active relapsing-remitting MS whose clinical course substantially improved following HIV infection and treatment. The patient achieved no evidence of disease activity status without any disease-modifying drugs. Both HIV-induced immunosuppression and antiretroviral therapy may have attenuated the clinical course in this patient.

The physician's duty of confidentiality is based on the observance of the patient's privacy and intimacy and on the importance of respecting both of these rights, thus creating a relationship of confidence and collaboration between doctor and patient. The main objective of this work consists of analyzing the aspects that are related to the confidentiality of patients' data with respect to the training, conduct and opinions of doctors from different Clinical Management Units of a third-level hospital via a questionnaire. The present study aimed to define the problem and determine whether the opinions of these professionals correspond to those observed in a previous work conducted at the same center. Of the 200 questionnaires that were collected, 62.5% were from consultants and the rest were from residents (37.5%) with an average of 14.4 ± 12.5 years in professional practice. The respondents noted habitual situations in which confidentiality was breached in the reference hospital (74%). The section on their attitudes and behaviors towards situations related to confidentiality showed a slightly lower average score than that of their medical knowledge; significant differences in these scores were observed between the consultants and residents as well as between the extreme age groups (≤ 30 vs. ≥ 51 years) and years of professional practice, thus more inadequate attitudes were consistently noted in younger doctors who had fewer years of experience. Finally, the respondents answered that the training of doctors in the aspects of healthcare law and ethics was the most important measure that the hospital could adopt regarding confidentiality practices.

The incidence of some types of tumours has increased progressively in recent years and is expected to continue growing in the coming years due in part to the aging of the population. The design of new therapies based on natural killer (NK) cells opens new possibilities especially for the treatment of elderly patients who are particularly susceptible to the toxicity of conventional chemotherapy treatments. In recent years, the potential use of NK cells in cancer immunotherapy has been of great interest thanks to advances in the study of NK cell biology. The identification of key points (checkpoints) in the activation of NK cells that can be regulated by monoclonal antibodies has allowed the design of new therapeutic strategies based on NK cells. However, there are still limitations for its use and the first clinical trials blocking KIR inhibitory receptors have shown little efficacy by inhibiting the maturation of NK cells. Blockade of other inhibitory receptors such as TIGIT, TIM3, LAG3 and PD1 may represent novel strategies to increase NK function in cancer patients. Altogether, the identification of NK cell and tumour cell markers of resistance or susceptibility to the action of NK cells will contribute to identifying those patients that will most likely benefit from NK cell-based immunotherapy.

Cancer is primarily considered a disease of old age. Immunosenescence refers to the age-associated changes in the immune system, and its contribution to the increased risk of cancer in old individuals has been discussed for many years. Natural killer (NK) cells are cytotoxic innate immune cells specialized in defence against tumour and virus-infected cells. NK cell cytotoxicity is the result of a fine balance between activating and inhibitory receptors. Several activating receptors have been identified that recognize different ligands frequently found over-expressed on tumour cells or virus-infected cells. The most important NK cell inhibitory receptors interact with major histocompatibility complex class I molecules expressed on almost all nucleated cells preventing NK cell-mediated lysis of healthy cells. NK cell immunosenescence is characterized by a redistribution of NK cell subsets, a diminished expression of several activating receptors and lower per-cell cytotoxicity. Altered expression of activating receptors has also been described in young and elderly cancer patients probably due to chronic exposure to ligands on tumour cells. Thus, the effect of both age and cancer may act synergistically to diminish NK cell-mediated tumour immunosurveillance. Different strategies harnessing the power of NK cells to target tumour cells have been designed including adoptive therapy with autologous or allogeneic expanded NK cells. In addition, checkpoint blockade of inhibitory receptors and the use of agonist antibodies to stimulate activating receptors are emerging areas of research. In this context, the effect of immunosenescence should be considered to improve the efficiency of cancer immunotherapy.

The role of natural killer (NK) cells in tumor immunosurveillance has been recently underlined. A better understanding of the receptor-ligand interactions between NK cells and solid tumor cells is essential for introducing more effective NK cell-based immunotherapy protocols into clinical practice. We previously analyzed the surface expression of ligands for NK cell-activating receptors and costimulatory molecules in a large panel of melanoma cell lines. Although the expression of ligands for NK cell-activating receptors is variable, the majority of melanoma cell lines express ligands for NKG2D and for DNAX accessory molecule-1 (DNAM-1). While the NKG2D receptor has been described as the principal entity responsible for the lysis of several melanoma cell lines, the role of natural cytotoxicity receptors (NCRs) and DNAM-1 receptors in NK cell recognition and killing of melanoma cells has been recently emphasized. Antibody-mediated masking of NKG2D, NCRs, and DNAM-1 has proven that NKG2D, NCRs, and DNAM-1 frequently cooperate in the lysis of melanoma cells. In this work, we provide an overview of recent advances in the study of melanoma cells' susceptibility to NK cell-mediated lysis and how multiple receptor-ligand interactions participate in melanoma cell elimination., (Copyright © 2011 S. Karger AG, Basel.)

Purpose: To evaluate the effectiveness, safety and predictability of the phakic intraocular lens (IOL) ZSAL-4 for correction of high myopia., Methods: In this retrospective study 28 IOL in 19 patientes were implanted. The following data were recorded, preoperatively, one week, one month, 3, 6 and 12 months postoperatively: spherical equivalent (SE), astigmatism, uncorrected visual acuity (UCVA), best corrected visual acuity (BCVA), endothelial cell density (CD), coefficient of variation (CV) and intraocular pressure (IOP). We performed LASIK in 3 eyes to correct a residual refractive defect., Results: The mean age was 29.7 S.D. 5.77 years and the mean following 7.62 S.D. 7.29 months. Six months postoperatively, the preoperative SE of -14.91 S.D. 2.88 was reduced to -1.29 S.D. 0.53; the BCVA varied from 0.56 S.D. 0.16 to 0.58 S.D. 0.12; the CD changed from 2670 S.D. 252 cells/mm2 to 2344 S.D. 262. The CV showed stability. The UCVA six months postoperatively was 0.39 S.D. 0.15. No eyes lost any line of BCVA; during the first month 63% of the eyes won 2 or more lines. The efficacy index was 0.83 S.D. 0.24 one month postoperatively and 0.63 S.D. 0.32 one year postoperatively; the safety index was 1.44 D.S. 0.34 and 1.30 S.D. 0.35 respectively. One IOL was explanted the second day due to pupilary blockage; 7 eyes had transient high IOP; 2 eyes developed pupilary ovalization and in 4 cases the IOL suffered some degree of rotation. One eye presented a flat retinal detachment one year postoperatively but with no other complications. The 3 eyes submitted to LASIK presented 0.8 of BCVA the third month after LASIK., Conclusions: ZSAL-4 IOL implantation is an effective and safe procedure with an acceptable predictability which, in some cases, could be improved with LASIK.

Mammalian histone gene transcription is increased approximately fivefold during the transition from the G1 phase to the S phase of the cell cycle. In this study, we present a detailed in vivo analysis of the human histone H2b promoter, which establishes that transcriptional regulation of this gene is mediated by a subtype-specific consensus element containing the core octanucleotide ATTTGCAT. Our results demonstrate that the activity of this sequence is specific for S phase. Comparative analysis of different replication variant mammalian histone gene promoters and our knowledge of the transcription factors interacting with the human histone H2b and H4 promoters allow us to conclude that coordinate regulation of histone gene transcription in higher eukaryotes is mediated by distinct factors. We propose a simple model for transcriptional regulation of mammalian histone gene expression, which incorporates both the distinct features of the individual histone gene promoters and the apparent functional equivalence of the specific sequence elements regulating transcription of each histone gene subtype.

Release of hormones from bovine anterior pituitary tissue in vitro was inveresly related to the osmolarity of the incubation medium. Addition of each of several ionic or non-ionic solutes to Krebs-Ringer-bicarbonate (KRB) or to beef serum inhibited hormone release. If the value of 286 mOsm/liter of KRB is considered as 100%, the osmolarity of the medium was altered from -15% to +10% of control. Over this range, an increase in osmolarity of 10% resulted in the following percentage inhibition: ACTH, 47; PRL, 43; TSH, 36; LH, 23; GH, 18; maximal percentage inhibition over this range was as follows: ACTH, 80; PRL, 60; TSH, 60; LH, 45; GH, 40. The inverse relationship between extracellular oxmolarity and secretion of ACTH and PRL would appear to be appropriate in view of the salt and water retaining actions of these hormones. The sensitivity of the response to osmotic changes suggests a possible role of body osmolarity in the regulation of adenohypophysial secretion.

In man, manganese neurointoxication is characterised in the early phase by behavior reminiscent of that observed in schizophrenia. During chronic manganese intoxication the neuropsychiatric symptoms manifested earlier disappear and are followed by a permanent neurological phase typified by extrapyramidal symptoms similar to those of Parkinson's disease. Study of manganese intoxication in animals may provide important clues towards elucidation of the biochemical defect underlying neuropsychiatric as well as extrapyramidal disease. Investigations in our laboratory suggest that neurotoxicity of manganese is an exaggeration of function in normal neuronal homeostasis. Manganese neurointoxication in neonatal rats resulted in significant depression of lipid peroxidation in several rat brain regions examined. In the striatum, lipid peroxidative activity was abolished, an effect which may be related to alteration in neurotransmitters often observed in the striatum of manganese treated rats. The chronic, extrapyramidal stage of manganism, may ensue when excess Mn2+ is oxidised to higher valency forms where it can potentiate the autoxidation of catecholamines, like dopamine, resulting in concomitant formation of free radicals and cytotoxic quinones. This latter effect may arise preferentially in the substantia nigra, where neuromelanin is formed nonenzymatically by autoxidation of dopamine.

Vanadium (V) as sodium orthovanadate induces an increase in lipid peroxidation in the kidneys after a single subcutaneous or intraperitoneal injection to rats or mice. The rate of malondialdehyde (MDA) formation, an index of lipid peroxidation, by kidney homogenates increased by more than 100% 1 h after injection. Chronic exposure of rats to vanadium sulfate, initially through maternal milk and later in the drinking water, resulted after 10 weeks in a significant increase in MDA formation by kidney but not by other tissues. In both acute and chronic studies in rats and mice, no significant increase in lipid peroxidation by V treatment was detected in brain, heart, lung, spleen, or liver. In mice, administration of ascorbate prior to acute exposure to V diminished both toxicity, i.e., respiratory depression and limb paralysis, and the formation of MDA in kidney.

Secretory granules containing prolactin (PRL) and growth hormone (GH) as essentially the only proteins were isolated by centrifugation. PRL and GH varied reciprocally in the granule preparations with the seasons. During winter PRL content was lowest (20%) and GH highest (80%); during summer the converse obtained: PRL, 70% and GH,, 30%. Both hormones were in almost equal proportion during the spring. The amount of either hormone released from granules and pituitary slices was directly related to its relative content in the gland. The pattern of PRL release from secretory granules and pituitary tissue in vitro was similar to that reported for blood levels in ruminants: low during winter and high during summer. It is concluded that seasonal factors affect primarily the synthesis and/or storage of PRL and GH, and there exists a direct relationship between intracellular stores and release.

Highly purified elastin was prepared from bovine ligamentum nuchae by hot alkali extraction. Antisera to the protein, developed against suspensions or acid solubilized preparations, were obtained from rabbits and guinea pigs. Of a large number of proteins, only insoluble elastin (from the aortae of several animal species) and tropoelastin, the putative soluble precursor, reacted with the antisera as determined by double antibody radioimmunoassay. Nanogram quantities of insoluble elastin can be detected following solubilization of the protein by brief acid treatment. Tropoelastin can be determined in the microgram range. The radioimmunoassay should permit determination in tissues, in fluids, and in in vitro cultures of soluble, newly synthesized elastin, mature insoluble elastin, and intermediate forms of the fibrous protein which may have heretofore escaped detection. A sensitive assay for elastin should also permit the acquisition of information concerned with connective tissue turnover during development, aging, and disease.

The content of endogenous morphine-like substance in bovine pituitary and brain was determined by an opiate radioreceptor assay. The intermediate lobe was most concentrated in activity and the brain least concentrated. Most of the endorphin is obtained in a 120 000 g-min fraction from pituitary or brain homogenates.

Endogenous substances that modulate the activity of (Na+ + K+)-ATPase through interaction at the cardiac glycoside site have been postulated. Reports of digitalis-like biological and immunological activity exhibited by certain ACTH/MSH peptides and 14-OH steroids make these compounds potential candidates as endogenous digitalis-like factors. We tested several ACTH/MSH peptides and 14 alpha-OH steroids in four in vitro assays and detected no significant cardiac glycoside-like activity. On the other hand, chlormadinone acetate, a progesterone derivative shown to bind with high affinity to the digitalis receptor, was nearly equipotent to digoxigenin in a [3H]ouabain radioreceptor assay. In a [3H]digoxin radioimmunoassay, however, digoxigenin and digoxin were equipotent but chlormadinone acetate was inactive. A clear dissociation between radioreceptor assay and radioimmunoassay activity was also observed using 15 beta-OH-progesterone. Our findings indicate that (a) ACTH/MSH peptides and 14 alpha-OH steroids are not viable candidates as endogenous digitalis-like factors, (b) digoxin antibodies are not necessarily directed at molecular determinants critical for biological activity, and (c) among the compounds reported to exhibit digitalis-like activity and postulated to share structural features with an endogenous steroidal digitalis-like factor, only chlormadinone acetate and its congeners appear to constitute tenable models.

Cells were dispersed from bovine anterior pituitary glands, by digestion with collagenase, and cultured. After 4 days the cell monolayers were incubated with fresh medium containing synthetic hypophysiotropic peptides for 2, 6, or 20 h, and hormone released into the medium was estimated by radioimmunoassay. After 2 h, thyroid releasing hormone (TRH) stimulated the release of thyroid-stimulating hormone (TSH) up to eightfold, and of prolactin (PRL) and follicle-stimulating hormone (FSH) about twofold at a minimal effective concentration of 1 ng/ml; enhanced growth hormone (GH) release was not apparent until 20 h, and release of luteinizing hormone (LH) and adrenocorticotrophic hormone (ACTH) was unaffected. Luteinizing hormone releasing hormone (LH-RH) enhanced release of LH maximally (three- to fourfold) during a 2 h incubation and was effective at 0.1 ng/ml; FSH release was significantly enhanced by about 50% above control level. Growth hormone release inhibiting hormone (GH-RIH)(somatostatin) showed significant effects only in the 20 h incubation; GH release was inhibited by 50% and release of PRL was slightly, but significantly, enhanced. Pituitary cell monolayers apparently permit maximal expression of releasing activities inherent in the hypothalamic hormones.

Androsterone sulfate (5alpha-androstan-3alpha-ol-17-one, 3-sodium sulfate) administered to freely moving rats via cerebroventricular cannulae induced analgesia, wet-dog shakes, body jerks, rigidity, Straub tail, hypermotility, excessive grooming, hyperreactivity to stimuli, aggression, escape behavior, EEG spiking, and behavioral and EEG seizures. These responses resemble those produced by certain opiate drugs and by beta-endorphin, an endogenous peptide; they appear during the 5-min infusion period, persist in some cases for several hours, and are diminished by pretreatment with the narcotic antagonist naloxone. These findings indicate that steroid hormones can act upon at least some of the same central pathways influenced by recognized opiate compounds.

Vanadate (Na3VO4) in micromolar concentrations enhanced the in vitro formation of adrenochrome from epinephrine, and of aminochrome from dopamine. Lipid peroxides in various tissues of the mouse and rat, particularly brain, were increased. Products of both catecholamine oxidation and lipid peroxidation may be the basis of the cardiotoxic and neurotoxic effects of vanadium.