McKittrick-Wheelock Syndrome Presenting with Acute Kidney Injury and Metabolic Alkalosis: Case Report and Narrative Review

A rare combination of severe volume depletion and electrolyte imbalance caused by a rectal villous adenoma is often referred to as the McKittrick-Wheelock syndrome. Patients usually seek medical care because of chronic hypersecretory diarrhea and display renal failure, metabolic acidosis, hyponatremia, and hypokalemia. We report the case of a 68-year-old woman who presented with this condition but showed unusual features such as severe hypokalemia and metabolic alkalosis, without diarrhea. She subsequently underwent transanal endoscopic microsurgery (TEMS), an innovative procedure in the management of large rectal adenomas. We also provide a narrative review of the literature on this rare entity

Evaluation of iTRAQ and SWATH-MS for the Quantification of Proteins Associated with Insulin Resistance in Human Duodenal Biopsy Samples

<div><p>Insulin resistance (IR) is associated with increased production of triglyceride-rich lipoproteins of intestinal origin. In order to assess whether insulin resistance affects the proteins involved in lipid metabolism, we used two mass spectrometry based quantitative proteomics techniques to compare the intestinal proteome of 14 IR patients to that of 15 insulin sensitive (IS) control patients matched for age and waist circumference. A total of 3886 proteins were identified by the iTRAQ (Isobaric Tags for Relative and Absolute Quantitation) mass spectrometry approach and 2290 by the SWATH-MS strategy (Serial Window Acquisition of Theoretical Spectra). Using these two methods, 208 common proteins were identified with a confidence corresponding to FDR < 1%, and quantified with p-value < 0.05. The quantification of those 208 proteins has a Pearson correlation coefficient (r²) of 0.728 across the two techniques. Gene Ontology analyses of the differentially expressed proteins revealed that annotations related to lipid metabolic process and oxidation reduction process are overly represented in the set of under-expressed proteins in IR subjects. Furthermore, both methods quantified proteins of relevance to IR. These data also showed that SWATH-MS is a promising and compelling alternative to iTRAQ for protein quantitation of complex mixtures.</p></div

Comparison of iTRAQ and SWATH using different approaches

<p>A) Scatter plot analysis of the 208 quantified proteins by iTRAQ and SWATH B) Volcano plot of SWATH ratios vs iTRAQ C) Comparison between SWATH and iTRAQ ratios for the 208 quantified proteins D) Density plot of iTRAQ and SWATH ratios for all differential ratios with p-value <0.05.</p

Workflow for discovery (iTRAQ) experiment.

<p>Duodenum biopsy samples were obtained from 15 IS volunteers and 14 IR patients. Samples were pooled and two technical replicates were generated.</p

Functional analyses.

<p>Bioinformatic analyses reveal that proteins involved in lipid metabolic process and oxydation-reduction processed are mostly underexpressed in insulin resistant patients.</p

Venn diagram showing the comparison between iTRAQ and SWATH.

<p>(A) Comparison in the number of protein identification at FDR<1% (B) Comparison in the number of proteins quantified at p-value <0.05.</p

SWATH workflow.

<p>Each condition is injected separately in a DDA mode to build the spectral library and in a SWATH mode. The spectral library built from the DDA runs is then used by PeakView and MarkerView to extract the peptide and the quantification information in each of the SWATH runs. BSA 1 fmol and 50 fmol was spiked in each SWATH run as an internal standard.</p