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71.
Shailja Tibrewal Ria Ratna Abha Gour Sumita Agarkar Suneeta Dubey Suma Ganesh Ramesh Kekunnaya Virender Sangwan Yutao Liu Vanita Vanita 《Indian journal of ophthalmology》2022,70(7):2280
Congenital aniridia is a pan ocular disorder characterized by partial or total loss of iris tissue as the defining feature. Classic aniridia, however, has a spectrum of ocular findings, including foveal hypoplasia, optic nerve hypoplasia, nystagmus, late-onset cataract, glaucoma, and keratopathy. The latter three are reasons for further visual compromise in such patients. This entity is often due to mutations in the PAX6 (Paired box protein Pax-6) gene. Recently, aniridia-like phenotypes have been reported due to non-PAX6 mutations as in PITX2, FOXC1, FOXD3, TRIM44, and CYP1B1 as well wherein there is an overlap of aniridia, such as iris defects with congenital glaucoma or anterior segment dysgenesis. In this review, we describe the various clinical features of classic aniridia, the comorbidities and their management, the mutation spectrum of the genes involved, genotype-phenotype correlation of PAX6 and non-PAX6 mutations, and the genetic testing plan. The various systemic associations and their implications in screening and genetic testing have been discussed. Finally, the future course of aniridia treatment in the form of drugs (such as ataluren) and targeted gene therapy has been discussed. 相似文献
72.
Pooja Sikka Vanita Suri Seema Chopra Neelam Aggarwal Subhas Chandra Saha Ramandeep Bansal Rajesh Vijayvergiya Ajay Bahl 《Texas Heart Institute journal / from the Texas Heart Institute of St. Luke's Episcopal Hospital, Texas Children's Hospital》2022,49(5)
Pregnancy in women with hypertrophic cardiomyopathy is not well described. In this retrospective study, we analyzed data on pregnant women with hypertrophic cardiomyopathy who were under follow-up care in the cardiology department of a tertiary care hospital. We reviewed data on all women registered in the hypertrophic cardiomyopathy cohort and those who attended the cardio-obstetric clinic and delivered between January 2010 and June 2019. From these 2 groups, we identified 7 pregnant women with hypertrophic cardiomyopathy who delivered during this period. These 7 women (mean [SD] age, 25 [3.3] years) had a total of 15 pregnancies (range per woman,1–4). This was a high-risk cohort, as 7 (46.7%) pregnancies were in the modified World Health Organization class III. The mean (SD) left ventricular wall thickness was 19.71 (2.56) mm in all pregnancies. Two of the 7 women with left ventricular outflow tract obstruction developed severe symptoms in the third trimester; these improved soon after delivery. Eight pregnancies without obstruction were well tolerated. Two pregnancies occurred after successful alcohol septal ablation. Both remained asymptomatic throughout pregnancy. All women tolerated labor well. Adverse maternal outcomes, including death, were not seen in any patient. All women who became symptomatic during pregnancy had relief of symptoms after delivery. Most women remained asymptomatic or had mild symptoms during pregnancy. Of the women with left ventricular outflow tract obstruction, 28.6% had severe symptoms that improved after delivery. Pregnancy was well tolerated after successful alcohol septal ablation. 相似文献
73.
74.
Sarbjit Vanita Jassal 《Peritoneal dialysis international》2015,35(6):630-634
Individuals aged over 70 years at the time of starting dialysis have a varied and often challenging existence on dialysis. Canadian data suggest those starting dialysis between the ages of 75 and 79 years will have an average life expectancy of 3.2 years, while based on US data, patients can expect an average life expectancy of 25 months. A substantial proportion of these patients will, however, experience transient or permanent loss of personal independence within the first few months to years on dialysis. Preliminary data from patients recently started on peritoneal dialysis (PD) suggest patients and families adapt, but that the adaptation often involves limiting activities and altering the social role the patient has within the family. As data emerge, it will be possible to hypothesize whether this adaptation is beneficial in the long term, or whether these adaptations are permissive, allowing the patient to play a sick role leading to an accelerated transition to frailty and possibly death. Future research will hopefully inform us whether the functional dependency can be identified early and whether it is preventable. In the interim, repair rather than prevention is possible through rehabilitation. We therefore advocate that programs providing PD care consider the integration of protocols whereby patients may undergo formal evaluation to identify those who would benefit from walking or personal care aids, rehabilitation interventions, and, when needed, personal support. 相似文献
75.
Donnie Eddins Terence G. Hamill Vanita Puri Christopher E. Cannon Jeffrey A. Vivian Sandra M. Sanabria-Bohórquez Jacquelynn J. Cook John A. Morrow Fiona Thomson Jason M. Uslaner 《Psychopharmacology》2014,231(3):511-519
Reduced NMDA receptor functioning is hypothesized to underlie the cognitive and negative symptoms associated with schizophrenia. However, because direct activation of the NMDA receptor is accompanied by neurotoxicity, mechanisms that activate the glycine co-agonist site on the NMDA receptor could carry greater therapeutic potential. In the current study, the effects of two glycine transporter 1 (GlyT1) inhibitors, RG1678 and ORG25935, were characterized in the object-retrieval detour (ORD) task in scopolamine-impaired rhesus monkeys and, using positron emission tomography (PET), the GlyT1 occupancy to efficacy relationship of each compound was established. Scopolamine exerted a significant decrease in accuracy in the ORD task. Lower doses of RG1678 (0.3 and 1.0 mg/kg, p.o.) significantly attenuated the impact of scopolamine, whereas the highest dose tested (1.8 mg/kg) did not. The predicted GlyT1 occupancies of RG1678 at the effective doses were ~10 and 30 %. ORG25935 (0.1, 0.3, and 1 mg/kg, p.o.) also significantly attenuated the impact of scopolamine on the ORD task, whereas 3 mg/kg did not. The predicted GlyT1 occupancies of ORG25935 at the effective doses ranged from 16 to 80 %. These data suggest that GlyT1 inhibitors have the potential to improve performance on prefrontal cortex-dependent tests such as the ORD task, but that efficacy is lost when higher occupancies are achieved. Importantly, recent Ph2B data published by Roche suggests that low but not high doses of RG1678 improved negative symptoms in patients with schizophrenia, highlighting the potential translational nature of the current preclinical findings. 相似文献
76.
Irene Ying Zoe Levitt Sarbjit Vanita Jassal 《Clinical journal of the American Society of Nephrology》2014,9(5):971-977
The burden of cognitive impairment appears to increase with progressive renal disease, such that the prevalence of dementia among those starting dialysis, or those already established on dialysis, is high. The appropriateness of dialysis initiation in this population has been questioned, and current Renal Physician Association guidelines suggest forgoing dialysis in individuals who have dementia and lack awareness of self and environment. Patients are, however, also entitled to equal rights and respect, equal access to health care services, and an opportunity to engage in shared decision-making processes, particularly if there is concern over reversibility of disease. This article discusses, on the basis of principles of beneficence and nonmaleficence, the arguments in favor of and against dialysis use, and the process of determining an appropriate care plan. Factors discussed include the current societal trend toward a technological imperative, premature fatalism, survival benefits, and the implications of providing care to patients who are unable to express their tolerance for symptoms associated with the treatment or lack of treatment. 相似文献
77.
78.
Michael V Hurley Nicola Walsh Vanita Bhavnani Nicky Britten Fiona Stevenson 《BMC musculoskeletal disorders》2010,11(1):31
Background
To explore the health beliefs, experiences, treatment and expectations of people with chronic knee pain, and investigate if, how and why these change after taking part on an integrated exercise-based rehabilitation programme - Enabling Self-management and Coping with Arthritis knee Pain through Exercise, ESCAPE-knee pain. 相似文献79.
Sahni V Léger Y Panaro L Allen M Giffin S Fury D Hamm N 《Environmental health perspectives》2007,115(12):1776-1779
CONTEXT: Manganese is a trace element, essential for physiologic functioning but neurotoxic at high doses. Common exposure sources include dietary intake as well as drinking water in some regions; toxicity is most often associated with inhalation exposures in occupational settings. In this article we describe the investigation of a pediatric case of manganism using both clinical and environmental assessment methods. CASE PRESENTATION: A previously healthy 6-year-old child presented with severe Mn neurotoxicity, iron deficiency, and elevated cobalt levels. Immediate and selected extended family members had elevated plasma Mn but remained asymptomatic. An exposure assessment identified seasonal ingestion exposures to Mn at the family's summer cottage; these were common to the four immediate family members. Well water used for drinking and cooking exceeded recommended guidelines, and foods high in Mn predominated in their diet. No inhalation exposures were identified. Only pica was unique to the patient. DISCUSSION: The combined evidence of the environmental assessment and biomonitoring of blood Mn levels supported a seasonal ingestion exposure source; this alone was insufficient to explain the toxicity because the patient's 7-year-old sibling was asymptomatic with almost identical exposures (except pica). A metabolic disorder involving divalent metals (Mn, Fe, and Co) interacting with environmental exposures is the most likely explanation. RELEVANCE TO CLINICAL OR PROFESSIONAL PRACTICE: This case report adds to the emerging body of evidence linking neurologic effects to ingestion Mn exposure. 相似文献
80.
Ciaraldi TP Phillips SA Carter L Aroda V Mudaliar S Henry RR 《The Journal of clinical endocrinology and metabolism》2005,90(10):5551-5558
CONTEXT: The insulin analog LysB3,GluB29-insulin (glulisine) displays accelerated in vivo bioavailability compared with native insulin. OBJECTIVE: Biological properties of this rapid-acting insulin analog were compared with the actions of native insulin and IGF-I. DESIGN: The effects of the hormones on hormone binding, glucose uptake, and thymidine uptake were evaluated in cultured human skeletal muscle cells. SETTING: This study was performed at a Veterans Administration hospital for patient characterization and tissue biopsies; in vitro studies were performed in a research laboratory. PATIENTS OR OTHER PARTICIPANTS: Skeletal muscle tissue was obtained from nondiabetic (n = 13) and type 2 diabetic (n = 14) subjects. INTERVENTION: Cultured skeletal muscle cells were treated acutely (15-90 min) or chronically (16 h) with varying concentrations of hormones. MAIN OUTCOME: The main study outcomes were measures of sensitivity (concentration required to attain 50% displacement of specific [125I]insulin or [125I]IGF-I bound and sensitivity (EC50) and potency (maximal response) for hormone binding and biological responses. RESULTS: Insulin and glulisine were comparable in their ability to displace insulin binding. Neither insulin nor glulisine competed efficiently for IGF-I binding. Insulin, glulisine, and IGF-I were equipotent in the stimulation of glucose uptake. Maximal stimulation of phosphorylation of Akt was greatest for IGF-I, whereas sensitivities were similar to those for glucose uptake. Sensitivities were comparable in muscle cells from nondiabetic and type 2 diabetic subjects. Stimulation of [3H]thymidine uptake was most responsive to IGF-I; insulin and glulisine were equally less effective, with sensitivities approximately 1-2% of that for IGF-I. Stimulation of p42/44 MAPK phosphorylation reflected the behavior of thymidine uptake. CONCLUSIONS: Although altered pharmacokinetics of glulisine can have therapeutic advantages, glulisine is indistinguishable from native insulin at the skeletal muscle level. 相似文献