Role of 99mTc-disofenin in duodenal and gastric aspirates in the evaluation of persistent neonatal cholestasis

A prospective study was undertaken on 49 infants with prolonged neonatal cholestasis to determine whether the specificity, sensitivity, and accuracy of 99mTc-disofenin scintigraphy can be improved by performing simultaneous radioactivity measurements on duodenal and gastric aspirates along with routine imaging. Specificity of routine scintigraphy was improved by this modification from 45.7 to 76.4%. Accuracy of the test was also superior in improving from 55% with routine scintigraphy to 78.4% by counting additional radioactivity on both duodenal and gastric aspirates. We suggest that this modified technique be applied in the evaluation of infants with conjugated hyperbilirubinemia so that invasive procedures such as open liver biopsy and operative cholangiogram may be avoided.     

Widened sutures in childhood meningitis: unrecognized sign of an acute illness.

Disagreement exists over the time for sutural widening to occur with increased intracranial pressure in children. Twenty-four children ranging in age from 2 months to 4 years with acute meningitis had skull films upon admission to C. S. Mott Children's Hospital. Nine of the children had widened sutures on initial skull films. Sutural widening was documented as early as 2 days after onset of meningitis. Occasionally, skull films may help in the diagnosis of meningitis.     

Fiberoptic transillumination: A new tool for the pediatric surgeon

Transillumination (TI) is a safe and reliable technique for evaluating masses or the presence of free air in the thorax or abdomen. TI can also be of help in the accurate placement of catheters or needles in the chest, abdomen, bladder, or vessels. Its use in several hundred cases has been documented by this report.     

Use of computerized tomography and chest x-rays in evaluating efficacy of aerosolized recombinant human DNase in cystic fibrosis patients younger than age 5 years: a preliminary study

The aim of this study was to evaluate the ability of high-resolution computerized tomography (HRCT) of the chest and chest x-rays (CXR) to determine efficacy of inhaled recombinant human DNase (rhDNase) in cystic fibrosis (CF) patients younger than 5 years of age. A randomized, double-blind, placebo-controlled pilot study of 12 patients with CF younger than 5 years of age, attending the University of Michigan Cystic Fibrosis Center (Ann Arbor, MI) was conducted. The changes in the HRCT and CXR score from baseline to day 100 of therapy were assessed using a previously validated scoring system. The mean changes of HRCT scores between the rhDNase and placebo groups were found to be significant at the 95% level, with mean change +/- SE mean of - 1.00 +/- 0.53 and 0.58 +/- 0.24 for rhDNase and placebo groups, respectively (P = 0.02). The difference in CXR score was not significant between the two groups. An analysis was performed to relate HRCT subscores to CXR score; only thickening of the intra-interlobular septae was significantly correlated with the total CXR score (r = - 0.7, P < 0.01). There was improvement in the parents' assessments of the patients' well-being, with improvement in physical activity, decreased cough, sleep quality, and appetite in those subjects receiving rhDNase. We conclude that the administration of rhDNase was associated with improvement in the HRCT scan in CF patients younger than 5 years of age. Findings indicate that HRCT of the chest is useful and sensitive in studying responses to therapy in patients with CF lung disease. To our knowledge, this is the first report of the use of HRCT to assess the effectiveness of a therapeutic modality in so young a CF patient population.     

Induction of Human Monocyte Interleukin (IL)-8 by Fibrinogen through the Toll-Like Receptor Pathway

Fibrinogen, in addition to its role in coagulation, is also an acute phase protein of inflammation. Treatment of adherent human monocytes with fibrinogen increases IL-8, IL-6, and TNF-α, but has no effect on MCP-1, IFN-β, or IP-10. Treatment of monocytes with fibrinogen and C5a doubles IL-8 and IL-6 production, compared to fibrinogen alone. The increase in cytokine production was accompanied by a transient increase in IL-8 mRNA and increased NF-κB activity. Monocytes from an IRAK-4- and two NEMO-deficient patients had 80% reduced IL-8 responses to fibrinogen. Moreover, responses to fibrinogen were blocked with anti-CD14 antibody (MY4), a subunit of the LPS receptor. The data indicate that fibrinogen alone and fibrinogen plus C5a are potent inducers of cytokine production in monocytes, and that signaling by fibrinogen is mediated through the TLR-4 pathway.     

Assessing Analytical Similarity of Proposed Amgen Biosimilar ABP 501 to Adalimumab

Background

ABP 501 is being developed as a biosimilar to adalimumab. Comprehensive comparative analytical characterization studies have been conducted and completed.

Objective

The objective of this study was to assess analytical similarity between ABP 501 and two adalimumab reference products (RPs), licensed by the United States Food and Drug Administration (adalimumab [US]) and authorized by the European Union (adalimumab [EU]), using state-of-the-art analytical methods.

Methods

Comprehensive analytical characterization incorporating orthogonal analytical techniques was used to compare products. Physicochemical property comparisons comprised the primary structure related to amino acid sequence and post-translational modifications including glycans; higher-order structure; primary biological properties mediated by target and receptor binding; product-related substances and impurities; host-cell impurities; general properties of the finished drug product, including strength and formulation; subvisible and submicron particles and aggregates; and forced thermal degradation.

Results

ABP 501 had the same amino acid sequence and similar post-translational modification profiles compared with adalimumab RPs. Primary structure, higher-order structure, and biological activities were similar for the three products. Product-related size and charge variants and aggregate and particle levels were also similar. ABP 501 had very low residual host-cell protein and DNA. The finished ABP 501 drug product has the same strength with regard to protein concentration and fill volume as adalimumab RPs. ABP 501 and the RPs had a similar stability profile both in normal storage and thermal stress conditions.

Conclusion

Based on the comprehensive analytical similarity assessment, ABP 501 was found to be similar to adalimumab with respect to physicochemical and biological properties.