International Journal of Paediatric Dentistry 2010; 20: 322–329
Background. Hurler Syndrome is associated with a deficiency of a specific lysosomal enzyme involved in the degradation of ...glycosaminoglycans. Hematopoietic stem cell transplantation (HSCT) in early infancy is undertaken to help prevent the accumulation of glycosaminoglycans and improve organ function.
Aim. To investigate the oral features and dental health of patients with Hurler Syndrome who have undergone successful HSCT.
Materials and methods. Twenty‐five patients (median age 8.6 years) post‐HSCT (mean age 9.4 months) underwent oral assessment (mean of 7.5 years post‐HSCT).
Results. Dental development was delayed. Numerous occlusal anomalies were noted including: open‐bite, class III skeletal base, dental spacing, primary molar infra‐occlusion and ectopic tooth eruption. Dental anomalies included hypodontia, microdontia, enamel defects, thin tapering canine crowns, pointed molar cusps, bulbous molar crowns and molar taurodontism. Tooth roots were usually short/blunted/spindle‐like in permanent molars. The prevalence of dental caries was low in the permanent dentition (mean DMFT 0.7) but high in the primary dentition (mean dmft 2.4). Oral hygiene instruction with plaque and or calculus removal was indicated in 71% of those that were dentate.
Conclusion. Patients with Hurler Syndrome post‐HSCT are likely to have delayed dental development, a malocclusion, and dental anomalies, particularly hypodontia and microdontia.
Previous studies suggest poor outcome in children with relapsed rhabdomyosarcoma (RMS). A better understanding is needed of which patients can be salvaged after first relapse.
The analysis included ...children with nonmetastatic RMS and embryonal sarcoma enrolled onto the International Society of Paediatric Oncology (SIOP) Malignant Mesenchymal Tumor (MMT) 84, 89, and 95 studies who relapsed after achieving complete local control with primary therapy. All patients included in the analysis had follow-up for ≥ 3.0 years after the last event. The clinical features, initial treatment characteristics, and features of the relapse were correlated with survival in univariate and multivariate analyses.
In all, 474 eligible patients were identified for the study. At ≥ 3.0 years from the last event, 176 (37%) were alive ("cured"). In a full-model multivariate analysis, the factors identified at first relapse that most strongly associated with poor outcome were metastatic relapse (odds ratio OR, 4.19; 95% CI, 2.0 to 8.5), prior radiotherapy treatment (OR, 3.64; 95% CI, 2.1 to 6.4), initial tumor size > 5 cm (OR, 2.53; 95% CI, 1.5 to 4.1), and time of relapse < 18 months from diagnosis (OR, 2.20; 95% CI, 1.3 to 3.6). Unfavorable primary disease site, nodal involvement at diagnosis, alveolar histology, and previous three- or six-drug chemotherapy were also independently associated with poor outcome. To estimate chance of cure for individual patients, a nomogram was developed, which allowed for weighting of these significant factors.
Some children with relapsed RMS remain curable. It is now possible to estimate the chance of salvage for individual children to direct therapy appropriately toward cure, use of experimental therapies, and/or palliation.
Allogeneic cord blood is now being widely used as a source of stem cells for hematologic reconstitution after myeloablative therapy, with reported significantly lower levels of graft-versus-host ...disease (GVHD) compared with the use of allogeneic bone marrow (BM). This study was undertaken to investigate biologic aspects of natural killer (NK) cell activity, as recognized effector cells of the GVHD and graft-versus-leukemia (GVL) response, from cord blood and conventional BM. NK-cell activity levels of freshly isolated cells from cord blood and BM against K562 targets were comparable. Lymphokine activated killer (LAK) cells from both hematopoietic cell sources were compared for their ability to kill target cells by necrotic or apoptotic mechanisms using specific target cell lines. Cord blood cells had significantly higher necrosis-mediated cytotoxic activity against Daudi target cells compared with BM-derived cells. Cord blood LAK cells had relatively high levels of apoptotic-mediated cytotoxicity against YAC-1 target cells, whereas BM-derived LAK cells were unable to induce apoptosis in these cells. Interleukin-2 (IL-2) induced significant granzyme B activity in cord cells in contrast to BM cells, in which very little activity was measured. Western blotting confirmed these findings, with IL-2 inducing granzyme B protein expression in cord cells but not detectable levels in BM cells. BM cells had significantly lower cell surface expression of IL-2R and prolonged culture in IL-2 was only partially able to restore their deficient apoptotic cytotoxic activity. Thus, major differences exist between cord blood-derived and BM-derived mononuclear cells with respect to their NK-cell–associated cytotoxic behavior. This could have important implications for stem cell transplantation phenomena, because it suggests that cord blood may have increased potential for a GVL effect.
Immune checkpoint inhibitors (ICI), increasingly used cancer therapeutics, can cause off-target inflammatory effects called immune-related adverse events (irAEs), including ICI-induced inflammatory ...arthritis (ICI-induced IA) and polymyalgia rheumatica (ICI-induced PMR). There are no validated classification criteria or outcome measures for these conditions, and adaptation of treatment recommendations from corresponding rheumatic diseases may not be appropriate. We summarized clinical descriptors of ICI-induced IA and ICI-induced PMR and aggregated domains used for these conditions in order to inform the development of a core set of outcome domains.
As the initial step of the core domain set generation process, we systemically searched Medline (Pubmed), EMBASE, Cochrane, and CINHL through March 2021 to identify all studies that provide both clinical descriptions and domains relevant to ICI-induced IA and ICI-induced PMR. Domains were mapped to core areas, such as pathophysiological manifestations, life impact, resource use, and longevity/survival, as suggested by the OMERACT 2.1 Filter.
We identified 69 publications, over a third of which utilized non-specific diagnoses of “arthritis,” “arthralgia,” and/or “PMR”. Other publications provided the number, the distribution and/or names of specific joints affected, while others labeled the irAE as the corresponding rheumatic disease, such as rheumatoid arthritis or spondyloarthritis. Most distinct domains mapped to the pathophysiology/manifestations core area (24 domains), such as signs/symptoms (13 domains), labs (6 domains), and imaging (5 domains), with harm domains of adverse effects from irAE treatment and fear of irAE treatment decreasing ICI efficacy. Forty-three publications also referenced irAE treatment and 35 subsequent response, as well as 32 tumor response.
There is considerable heterogeneity in the domains used to clinically characterize ICI-induced IA and ICI-induced PMR. There were several domains mapped to the pathophysiologic manifestations core area, although several publications highlighted domains evenly distributed among the other core areas of life impact, longevity/survival and resource use.
Background: Hormone replacement therapy (HRT) is typically avoided for women with a history of breast cancer because of concerns that estrogen will stimulate recurrence. In this study, we sought to ...evaluate the impact of HRT on recurrence and mortality after a diagnosis of breast cancer. Methods: Data were assembled from 2755 women aged 35–74 years who were diagnosed with incident invasive breast cancer while they were enrolled in a large health maintenance organization from 1977 through 1994. Pharmacy data identified 174 users of HRT after diagnosis. Each HRT user was matched to four randomly selected nonusers of HRT with similar age, disease stage, and year of diagnosis. Women in the analysis were recurrence free at HRT initiation or the equivalent time since diagnosis. Rates of recurrence and death through 1996 were calculated. Adjusted relative risks were estimated by use of the Cox regression model. All statistical tests were two-sided. Results: The rate of breast cancer recurrence was 17 per 1000 person-years in women who used HRT after diagnosis and 30 per 1000 person-years in nonusers (adjusted relative risk for users compared with nonusers = 0.50; 95% confidence interval CI = 0.30 to 0.85). Breast cancer mortality rates were five per 1000 person-years in HRT users and 15 per 1000 person-years in nonusers (adjusted relative risk = 0.34; 95% CI = 0.13 to 0.91). Total mortality rates were 16 per 1000 person-years in HRT users and 30 per 1000 person-years in nonusers (adjusted relative risk = 0.48; 95% CI = 0.29 to 0.78). The relatively low rates of recurrence and death were observed in women who used any type of HRT (oral only = 41% of HRT users; vaginal only = 43%; both oral and vaginal = 16%). No trend toward lower relative risks was observed with increased dose. Conclusion: We observed lower risks of recurrence and mortality in women who used HRT after breast cancer diagnosis than in women who did not. Although residual confounding may exist, the results suggest that HRT after breast cancer has no adverse impact on recurrence and mortality.
The abundance, activity and species richness of arthropods, particularly of insect herbivores, were investigated in the upper canopy and understorey of a lowland rainforest at La Makandé, Gabon. In ...total 14 161 arthropods were collected with beating, flight interception and sticky traps, from six canopy sites, during the day and at night, from mid-January to mid-March 1999. The effects of stratum were most important, representing between 40 and 70% of the explained variance in arthropod distribution. Site effects represented between 20 and 40% of the variance and emphasized the need for replication of sampling among canopy sites. Time effects (diel activity) explained a much lower percentage of variance (6–9%). The density and abundance of many arthropod taxa and species were significantly higher in the upper canopy than in the understorey. Arthropod activity was also higher during the day than at night. In particular, insect herbivores were 2.5 times more abundant and twice as speciose in the upper canopy than in the understorey, a probable response to the greater and more diverse food resources in the former stratum. Faunal overlap between the upper canopy and understorey was low. The most dissimilar herbivore communities foraged in the understorey at night and the upper canopy during the day. Further, a taxonomic study of a species-rich genus of herbivore collected there Agrilus, Coleoptera Buprestidae) confirmed that the fauna of the upper canopy was different, diverse and very poorly known in comparison to that of the understorey. Herbivore turnover between day and night was rather high in the upper canopy and no strong influx of insect herbivores from lower foliage to the upper canopy was detected at night. This suggests that insect herbivores of the upper canopy may be resident and well adapted to environmental conditions there.
PDF
