Organoids as a Model for Colorectal Cancer

Modelling human diseases in in vitro systems is undisputedly an invaluable research tool, yet there are many limitations. Some of those limitations have been overcome through the introduction of organoid culture systems, which have revolutionised colorectal cancer research and enabled an array of new experimental techniques. This 3D system models the physiology, shape, dynamics and cell make-up of the intestinal epithelium producing a relevant and highly adaptable model system. The increased functional relevance of this model compared to the use of 2D cancer cell lines makes it an invaluable tool for both basic and translational research. As the limitations of this system are being overcome to make high-throughput assays possible, it is clear that organoids are becoming a mainstay of colorectal cancer research. This review aims to explore the advantages and limitations of this system and discusses the future directions enabled by this model.     

Trading risks for markets: The international harmonisation of pharmaceuticals regulation

Drawing on interviews and documentary research, this paper explores the nature of international harmonisation of pharmaceutical regulation. The relationships between international harmonisation, trade interests in market expansion and the regulatory state are examined. Particular attention is given to the implications of this harmonisation for drug safety, risk assessment and public health. It is argued that this process is lowering regulatory standards regarding drug safety and is making the regulatory state more vulnerable to capture by industrial interests. This is accentuated by the misrepresentation of societal and political judgements as technical calculations and a concomitant lack of public accountability.     

Anterior spine fusion using Zielke instrumentation for adult thoracolumbar and lumbar scoliosis

Analysis of adult patients undergoing anterior spine fusions with Zielke instrumentation between January 1983 and November 1986 was performed. Objectives were to review results of surgical treatment and identify factors affecting results. Charts, 3 foot standing anteroposterior and lateral and supine maximal side bending radiographs were reviewed. Subjective data were obtained by telephone. There were 26 patients, average age 41 years. Average radiographic follow-up was 48 months. Indications were pain and curve progression. Average correction was 63% of the instrumented curve. Average change of lordosis was 8 degrees and kyphosis was 6 degrees. Apical vertebral rotation corrected an average of 37%. Complications were: eight hardware failures, one deep infection, and two psychiatric events. The high-risk groups: curves greater than 60 degrees, patients older than 50 years of age, and rigid curves.     

Familial hypocalciuric hypercalcaemia and pancreatitis: no causal link proven

A case of a patient with pancreatitis and familial hypocalciuric hypercalcaemia is presented and the literature linking FHH and pancreatitis is reviewed. The case for a causal link between the two conditions is not proven and seems unlikely. In view of this we strongly challenge the recommendation of total parathyroidectomy in such cases.     

Ultrastructural study of the liver in argininosuccinase deficiency

The liver of a 19-year-old woman with argininosuccinase deficiency was studied ultrastructurally under conditions for excellent tissue fixation. Dilated smooth endoplasmic reticulum and mitochondrial crystalloids were the most prominent abnormalities found. These features were compared to fine-structural abnormalities found in other disorders of the Krebs-Henseleit pathway. No change was considered specific or related to subcellular enzyme localization.     

Comparison of intraarterial and IV gadolinium-enhanced MR angiography with digital subtraction angiography for the detection of renal artery stenosis in pigs.

OBJECTIVE: Catheter-based intraarterial injections of gadolinium are useful during MR imaging-guided endovascular procedures to generate rapid vascular road maps. Using an animal model of renal artery stenosis, we tested the hypothesis that intraarterial gadolinium-enhanced MR angiography is as accurate as IV gadolinium-enhanced MR angiography and digital subtraction angiography (DSA). We also tested the hypothesis that intraarterial MR angiography uses less gadolinium than IV MR angiography. MATERIALS AND METHODS: We induced bilateral renal artery stenosis in five pigs. All pigs underwent comparative imaging with DSA, IV MR angiography, and aortic catheter-directed intraarterial MR angiography. For IV and intraarterial MR angiography, we used the same three-dimensional acquisition. We assessed differences in quantitative stenosis measurements among DSA, IV MR angiography, and intraarterial MR angiography using the Wilcoxon's signed rank test. RESULTS: Mean stenosis measurements (+/-SD) were as follows: DSA, 58% +/- 12%; IV MR angiography, 63% +/- 9.3%; and intraarterial MR angiography, 64% +/- 11%. There were no statistically significant differences in accuracy between DSA and IV MR angiography (p = 0.06), DSA and intraarterial MR angiography (p = 0.16), or IV and intraarterial MR angiography (p = 0.70). Intraarterial MR angiography used a mean gadolinium dose of 5.6 mL, compared with 9 mL for IV MR angiography. CONCLUSION: In swine, IV and intraarterial MR angiography have a similar accuracy for detecting renal artery stenosis. Intraarterial MR angiography uses smaller doses of injected gadolinium.     

The prevalence of overmedication with levothyroxine in ambulatory elderly patients

Objective To estimate the prevalence of overmedication with levothyroxine in ambulatory elderly patients and to determine if this older patient population is inherently more likely to have suppressed serum TSH concentration. Research design and methods The medical records of 180 elderly men above the age of 60 years who were on levothyroxine therapy were reviewed. The prevalence of suppressed TSH as measured by a supersensitive assay in 935 ambulatory patients in a Department of Veterans Affairs Medical Center and 214 unselected elderly subjects presenting to a health fair was also evaluated. Concomitant free T₄ measurements done with a competitive binding assay kit were available in 381 patients. Results The overall prevalence of low serum TSH levels among patients on levothyroxine therapy followed up in an academic center is 13,3%. Patients seen in general medicine (8.7%) and geriatric clinic (7.7%) had the lowest rates of overreplacement with thyroid hormone compared to other medical subspecialty clinics (16.7%). There was a significant correlation between levothyroxine dose used and serum free T₄, TSH or log TSH values. The prevalence of low TSH in elderly subjects without known history of thyroid disease was 1.7% in the community and 3.1% in patients seen in clinics. The sensitivity of the pituitary thyrotrophs to thyroid hormone was not increased in elderly patients. Conclusions The prevalence of overmedication with levothyroxine in elderly patients is high, especially in those seen in community clinics. The suppressed serum TSH levels in elderly patients on levothyroxine is the result of overdosage rather than secondary to increased pituitary gland sensitivity to thyroid hormone.