An in vitro model for abnormal skeletal development in the lysosomal storage diseases

Lysosomal storage diseases such as G_M1-gangliosidosis are associated with skeletal abnormalities. Radiological and histological studies, both in human and corresponding animal models, indicate retarded bone formation. Since cartilage maturation leads to bone formation, we developed an in vitro system to study and compare the biological features of cartilage from dogs affected with G_M1-gangliosidosis with age-matched controls. Costochondral chondrocytes were grown in monolayer and in agarose culture. Both affected and control cells dedifferentiated in monolayer; however, in agarose culture they re-expressed the chondrocytic phenotype. Cells from affected dogs were enlarged and contained numerous large vaculoes when compared with control cells. This morphology was similar to that seen in vivo. In addition, the affected cells appeared to have a reduction in mitosis and alcian blue staining proteoglycans. Cultures from affected animals contained fewer cells positive for alkaline phosphatase activity. Both affected and control cells expressed collagen types I and II and were positive for the lectin Ricinus communis agglutinin-I. However, the staining of the control culture for type II collagen was more prominent than in the affected cells. These findings suggest that culture of chondrocytes in agarose may be a useful method for studying the biology of cartilage which leads to skeletal abnormalities in lysosomal storage diseases.     

Early life body size in relation to risk of renal cell carcinoma in adulthood: a Danish observational cohort study

European Journal of Epidemiology - Adult obesity increases risks of renal cell carcinoma (RCC). This study investigated if birth weight, child body mass index (BMI) and height are associated with...     

Potential impact of COVID-19 pandemic on vaccination coverage in children: A case study of measles-containing vaccine administration in the United States (US)

BackgroundThe COVID-19 pandemic and stay-at-home orders have caused an unprecedented decrease in the administration of routinely recommended vaccines. However, the impact of this decrease on overall vaccination coverage in a specific birth cohort is not known.MethodsWe projected measles vaccination coverage for the cohort of children becoming one year old in 2020 in the United States, for different durations of stay-at-home orders, along with varying catch-up vaccination efforts.ResultsA 15% sustained catch-up rate outside stay-at-home orders (compared to what would be expected via natality information) may be necessary to achieve projected vaccination coverage similar to previous years. Permanent decreases in vaccine administration could lead to projected vaccination coverage levels below 80%.ConclusionModeling measles vaccination coverage under a range of scenarios provides useful information about the potential magnitude and impact of under-immunization. Sustained catch-up efforts are needed to assure that measles vaccination coverage remains high.     

To treat or not to treat a newborn child with severe brain damage? A cross-sectional study of physicians’ and the general population’s perceptions of intentions

Ethical dilemmas are common in the neonatal intensive care setting. The aim of the present study was to investigate the opinions of Swedish physicians and the general public on treatment decisions regarding a newborn with severe brain damage. We used a vignette-based questionnaire which was sent to a random sample of physicians (n = 628) and the general population (n = 585). Respondents were asked to provide answers as to whether it is acceptable to discontinue ventilator treatment, and when it actually is discontinued whether or not it was acceptable to use drugs which hasten death unintentionally or intentionally. The response rate was 67 % of physicians and 46 % of the general population. A majority of both physicians [56 % (CI 50–62)] and the general population [53 % (CI 49–58)] supported arguments for withdrawing ventilator treatment. A large majority in both groups supported arguments for alleviating the patient’s symptoms even if the treatment hastened death, but the two groups display significantly different views on whether or not to provide drugs with the additional intention of hastening death, although the difference disappeared when we compared subgroups of those who were for or against euthanasia-like actions. The study indicated that physicians and the general population have similar opinions regarding discontinuing life-sustaining treatment and providing effective drugs which might unintentionally hasten death but seem to have different views on intentions. The results might be helpful to physicians wanting to examine their own intentions when providing adequate treatment at the end of life.     

Invasion characteristics of oral tongue cancer

BACKGROUND:

The 2000 College of American Pathologists (CAP) guidelines recommend that a characterization of carcinomas of the upper aerodigestive tract, including tongue cancer, should include depth of invasion (DI) and the presence of lymphovascular invasion (LVI) or perineural invasion (PNI).

METHODS:

This study included patients who were diagnosed with cancer of the oral tongue, who underwent tumor resection, and who were reported to either the Metropolitan Atlanta and Rural Georgia Surveillance, Epidemiology, and End Results (SEER) registry or the Los Angeles SEER registry. The authors assessed the completeness of pathology reporting with respect to the documentation of PNI or LVI and DI. Generalized estimating equations were used to examine factors that influenced reporting while taking into consideration clustering of observations within the hospitals. Univariate and multivariate survival analyses were conducted to examine the impact of tumor invasion characteristics on mortality while controlling for other prognostic factors.

RESULTS:

DI reporting increased from 13% between 1997 and 1999 to 23% between 2000 and 2004 after the CAP issued its recommendations; whereas mode of invasion (the presence of LVI and/or PNI) reporting for the same period increased from 13% to 38%. The observed increase in reporting was most pronounced in the first 2 years (2000 and 2001) and appeared to decline again afterward. Tumor invasion >3 mm in depth and the presence of PNI were among the strongest predictors of survival in multivariate analyses.

CONCLUSIONS:

The current results indicated the importance of reporting tumor invasion characteristics for patients diagnosed with cancer of the oral tongue. The findings also underscore the need for continuous monitoring of adherence to the CAP protocol. Cancer 2009. © 2009 American Cancer Society.