Oral sensation (including two-point discrimination, oral stereognosis, vibrotactile detection, somesthetic sensitivity, proprioception, and thermal sensitivity) was studied in 60 healthy adults in five age categories: 20 to 34, 35 to 49, 50 to 64, 65 to 79, and 80 years and above. Thermal and somesthetic sensitivity as well as proprioception did not change with age. Ability to differentiate tactile and vibratory sensation on the lip decreased after age 80 (P less than .01), but vibration detection on the soft palate did not change. Stereognostic ability remained good up to age 80, and then declined for four of the nine shapes tested (P less than .01). Two-point discrimination deteriorated on the upper lip (P less than .01), on the cheeks (P less than .02), and on the lower lip (P less than .06). Two-point discrimination on the tongue and palate did not change. It was noted that oral sensation remained good with aging, showing only a slight decline in function after age 80.
SUMMARY Standing height, sitting height, and leg length were measured in 79 patients (aged 16-30 years), who had been given craniospinal irradiation (n=37) or cranial irradiation (n=42) in childhood for a brain tumour and had completed their growth. Their measurements were compared with established standards for sitting height and leg length in British children (aged 16-18 years). To examine the effects of spinal irradiation on spinal growth independent of growth hormone deficiency we analysed the leg length (LL) minus sitting height (SH) standard deviation score (SDS) and used the cranial group as controls. There was an overall significant difference between the median craniospinal LL-SH SDS (1-98) and the median cranial LL-SH SDS (0-545). Within the craniospinal group there was a significant correlation with age at treatment, but there was no such correlation for the cranial group. After splitting age at treatment into three groups (0<5, 5<10, and 10-15 years) there was a significant difference between the LL-SH SDS of the craniospinal and cranial groups for each of the age ranges.In conclusion, spinal irradiation has a profound effect on spinal growth and the younger the child is when given irradiation the greater the subsequent skeletal disproportion. Our most conservative figures indicate that the eventual loss in height is 9 cm when irradiation is given at 1 year, 7 cm when given at 5 years, and 5-5 cm when given at 10 years.
BackgroundReprogramming of cardiac fibroblasts into induced cardiomyocyte‐like cells represents a promising potential new therapy for treating heart disease, inducing significant improvements in postinfarct ventricular function in rodent models. Because reprogramming factors effective in transdifferentiating rodent cells are not sufficient to reprogram human cells, we sought to identify reprogramming factors potentially applicable to human studies.Methods and ResultsLentivirus vectors expressing Gata4, Mef2c, and Tbx5 (GMT); Hand2 (H), Myocardin (My), or microRNA (miR)‐590 were administered to rat, porcine, and human cardiac fibroblasts in vitro. induced cardiomyocyte‐like cell production was then evaluated by assessing expression of the cardiomyocyte marker, cardiac troponin T (cTnT), whereas signaling pathway studies were performed to identify reprogramming factor targets. GMT administration induced cTnT expression in ≈6% of rat fibroblasts, but failed to induce cTnT expression in porcine or human cardiac fibroblasts. Addition of H/My and/or miR‐590 to GMT administration resulted in cTNT expression in ≈5% of porcine and human fibroblasts and also upregulated the expression of the cardiac genes, MYH6 and TNNT2. When cocultured with murine cardiomyocytes, cTnT‐expressing porcine cardiac fibroblasts exhibited spontaneous contractions. Administration of GMT plus either H/My or miR‐590 alone also downregulated fibroblast genes COL1A1 and COL3A1. miR‐590 was shown to directly suppress the zinc finger protein, specificity protein 1 (Sp1), which was able to substitute for miR‐590 in inducing cellular reprogramming.ConclusionsThese data support porcine studies as a surrogate for testing human cardiac reprogramming, and suggest that miR‐590‐mediated repression of Sp1 represents an alternative pathway for enhancing human cardiac cellular reprogramming.
Purpose Thalidomide, originally developed as a sedative, was subsequently identified to have antiangiogenic properties. Lenalidomide is an antiangiogenic and immunomodulatory agent that has been utilized in the treatment of patients with brain tumors. We studied the pharmacokinetics and cerebrospinal fluid (CSF) penetration of thalidomide and lenalidomide in a nonhuman primate model. Methods A dose of 50 mg of thalidomide or 20 mg of lenalidomide were administered once orally to each of three rhesus monkeys. Plasma and CSF samples were obtained at specified intervals and the thalidomide or lenalidomide concentrations were determined by high-performance liquid chromatography with tandem mass spectrometry. Pharmacokinetic parameters were estimated using noncompartmental methods. CSF penetration was calculated as area under the concentration-time curve (AUC) CSF/AUC plasma. Results For thalidomide, the median apparent clearance (Cl/F) was 2.9 mL/min/kg, the median plasma AUC was 80 µM•hr, and the median terminal half-life (t½) was 13.3 hours. For lenalidomide, the median Cl/F was 8.7 mL/min/kg, the median AUC was 9 µM•hr, and the median t½ was 5.6 hours. Thalidomide was detected in the CSF of all animals, with a median penetration of 42%. Lenalidomide was detected in the CSF of 2 of 3 animals, with a CSF penetration of 11% in each. Conclusion Thalidomide and lenalidomide penetrate into the CSF after oral administration of clinically relevant doses. Plasma exposure to lenalidomide was similar in our model to that observed in studies involving children who have brain tumors. These results support further development of lenalidomide for the treatment of central nervous system malignancies.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.