Claudin-containing exosomes in the peripheral circulation of women with ovarian cancer

<p>Abstract</p> <p>Background</p> <p>The absence of highly sensitive and specific serum biomarkers makes mass screening for ovarian cancer impossible. The claudin proteins are frequently overexpressed in ovarian cancers, but their potential as prognostic, diagnostic, or detection markers remains unclear. Here, we have explored the possible use of these proteins as screening biomarkers for ovarian cancer detection.</p> <p>Methods</p> <p>Claudin protein shedding from cells was examined by immunoblotting of conditioned culture media. The presence of claudins in exosomes released from ovarian cancer cells was demonstrated by sucrose gradient separation and immunogold electron microscopy experiments. Claudin-4-containing exosomes in the plasma of ovarian cancer patients were evaluated in a pilot panel of 63 ovarian cancer patients and 50 healthy volunteers. The CA125 marker was also assessed in these samples and compared with claudin-4 positivity.</p> <p>Results</p> <p>We show that full-length claudins can be shed from ovarian cancer cells in culture and found in the media as part of small lipid vesicles known as exosomes. Moreover, 32 of 63 plasma samples from ovarian cancer patients exhibited the presence of claudin-4-containing exosomes. In contrast, only one of 50 samples from individuals without cancer exhibited claudin-4-positive exosomes. In our small panel, at a specificity of 98%, the claudin-4 and CA125 tests had sensitivities of 51% and 71%, respectively. The two tests did not appear to be independent and were strongly correlated.</p> <p>Conclusion</p> <p>Our work shows for the first time that claudin-4 can be released from ovarian cancer cells and can be detected in the peripheral circulation of ovarian cancer patients. The development of sensitive assays for the detection of claudin-4 in blood will be crucial in determining whether this approach can be useful, alone or in combination with other screening methods, for the detection of ovarian cancer.</p

Acute Management of Renal Colic and Compliance with National Standards: Closure of the Audit Loop

Renal (ureteric) colic is a common surgical emergency. It is usually caused&nbsp; by&nbsp; calculi&nbsp; obstructing&nbsp; the&nbsp; ureter,&nbsp; but&nbsp; about&nbsp; 15%&nbsp; of&nbsp; patients have&nbsp; other&nbsp; causes,&nbsp; e.g.&nbsp; extrinsic&nbsp; compression,&nbsp; intramural&nbsp; neoplasia or an anatomical abnormality [1]. Up to 12 percent of the population will&nbsp; have&nbsp; a&nbsp; urinary&nbsp; stone&nbsp; during&nbsp; their&nbsp; lifetime,&nbsp; and&nbsp; recurrence&nbsp; rates approach&nbsp; 50&nbsp; percent&nbsp; [2].&nbsp; Fifty-five&nbsp; percent&nbsp; of&nbsp; those&nbsp; with&nbsp; recurrent stones have a family history of urolithiasis [3] and having such a history increases the risk of stones by a factor of three [4]. Upon presentation to the A&amp;E department, suspected acute renal colic patients must have a&nbsp; clinical&nbsp; examination&nbsp; and&nbsp; radiological&nbsp; investigations&nbsp; to&nbsp; confirm&nbsp; the diagnosis [5]. The&nbsp; best&nbsp; imaging&nbsp; study&nbsp; to&nbsp; confirm&nbsp; the&nbsp; diagnosis&nbsp; of&nbsp; a&nbsp; urinary stone&nbsp; in&nbsp; a&nbsp; patient&nbsp; with&nbsp; acute&nbsp; flank&nbsp; pain&nbsp; is&nbsp; unenhanced,&nbsp; helical&nbsp; CT&nbsp; of the&nbsp; abdomen&nbsp; and&nbsp; pelvis&nbsp; [6].&nbsp; If&nbsp; CT&nbsp; is&nbsp; unavailable,&nbsp; plain&nbsp; abdominal radiography&nbsp; should&nbsp; be&nbsp; performed,&nbsp; since&nbsp; 75&nbsp; to&nbsp; 90&nbsp; percent&nbsp; of&nbsp; urinary calculi are radiopaque [5]. Although ultrasonography has high specificity (greater than90 percent), its sensitivity is much lower than that of CT, typically in the range of 11 to24 percent [5]. Thus, ultrasonography is not&nbsp; used&nbsp; routinely&nbsp; but&nbsp; is&nbsp; appropriate&nbsp; as&nbsp; the&nbsp; initial&nbsp; imaging&nbsp; test&nbsp; when colic occurs during pregnancy [7]. </p

Parathyroidectomies: Pre and Post Op Usage of Calcium Supplementation and Effect on Calcium Levels

Introduction: PTH is released from the parathyroid glands behind the thyroid and is the primary regulator of calcium homeostasis. Indications for surgery in hyperparathyroidism remain controversial but&nbsp; can&nbsp; include&nbsp; symptomatic&nbsp; disease,&nbsp; renal&nbsp; stones,&nbsp; impaired&nbsp; renal&nbsp; function,&nbsp; bone&nbsp; involvement&nbsp; or marked&nbsp; reduction&nbsp; in&nbsp; bone&nbsp; density.&nbsp; Due&nbsp; to&nbsp; hypocalcaemia&nbsp; post&nbsp; op,&nbsp; pre-op&nbsp; calcium&nbsp; loading&nbsp; should occur. However not much research has been conducted into this area. Methods: We retrospectively reviewed notes of patients with hyperparathyroidism secondary to renal failure admitted to a single centre, single surgeon, for parathyroidectomies. The following were determined: calcium preloading (type and dose) in secondary hyperparathyroidism, average calcium level&nbsp; on&nbsp; admission&nbsp; and&nbsp; post&nbsp; op,&nbsp; for&nbsp; preloaded&nbsp; and&nbsp; non-loaded&nbsp; secondary&nbsp; hyperparathyroid&nbsp; cases.This&nbsp; was&nbsp; also&nbsp; determined&nbsp; for&nbsp; primary&nbsp; hyperparathyroidism&nbsp; and&nbsp; renal&nbsp; transplant&nbsp; cases.&nbsp; Notes&nbsp; were also&nbsp; reviewed&nbsp; for&nbsp; oral&nbsp; calcium&nbsp; supplementation&nbsp; or&nbsp; IV&nbsp; calcium&nbsp; supplemenyation&nbsp; (type&nbsp; and&nbsp; average dose), for preloaded/ non preloaded cases, primary cases and new transplants. Length of stay was also reviewed. Statistical differences will be calculated. </p