Topically administered Risedronate shows powerful anti-osteoporosis effect in ovariectomized mouse model

We investigated the therapeutic effect of topical Risedronate (RIS) on a mouse model of estrogen-deficient osteoporosis. Fourteen-week-old female mice were ovariectomized and assigned to 4 groups: SHAM-operated (SHAM), OVX mice treated with vehicle (OVX-V), OVX mice treated with 0.2% RIS (OVX-0.2% RIS), and OVX-mice treated with 0.02% RIS (OVX-0.02% RIS). Topical samples containing RIS were prepared in 10% (w/w) polyethylene glycol (PEG, MW 400) and 80 μg of sample was spread on the mice's mid-backs every 3 days for 5 weeks. Micro-CT analysis of femora demonstrated that OVX-0.2% RIS exhibited a 29% greater bone mineral density and 24% greater bone volume fraction than that of OVX-V group. Investigation of the trabecular bone in OVX-0.2% RIS revealed a 24% higher bone volume (BV/TV), 51% higher trabecular number (Tb.N), and 40% lower trabecular separation (Tb.Sp) compared to OVX-V mice. Additionally, bone phenotypes of tibiae were further confirmed by histological analysis. OVX-0.2% RIS group exhibited a 494% greater BV/TV, 464% less Tb.Sp, 81% greater active osteoclast surface (Oc.S/BS) and 26% less osteoclast number (N.Oc/BS) than that of OVX-V group. Collectively, these results indicated that topical delivery of RIS has powerful pharmaceutical effects on the prevention of osteoporosis and bone turnover.     

Impact of Combined Prophylactic Unilateral Central Neck Dissection and Hemithyroidectomy in Patients with Papillary Thyroid Microcarcinoma

Background  

Lymph node metastases occur frequently in patients with papillary thyroid carcinoma (PTC), and the central compartment of the neck is the most frequently involved site. Some authors advocate prophylactic central neck dissection (CND) during total thyroidectomy. However, little is known about the effects of prophylactic unilateral CND in papillary thyroid microcarcinoma (PTMC) patients who undergo hemithyroidectomy. This study was designed to investigate the impact of prophylactic unilateral CND in this population.     

The washout rate on the delayed CT image as a diagnostic tool for adrenal adenoma verified by pathology: a multicenter study

Objectives

To establish the undisputed the value of washout rate for adrenal adenoma using delayed enhanced CT, we evaluated diagnostic performance of cut-off value and delayed time of washout rate by final pathologic diagnosis in a multicenter study.

Methods

We reviewed the pathologic and clinical records of 244 patients underwent adrenalectomies at 5 university hospitals between 2005 and 2009. We calculated the mean Housfield units (HU) of adrenal lesion at non-enhancing CT, and early and delayed enhanced CT using the region of interest. We used ROC curves to determine the specificity and sensitivity of non-enhanced CT scans and the washout rate according to the various cut-off for adrenal adenomas.

Results

We divided the patients into adrenal adenoma group (n?=?138) and non-adrenal adenoma group (n?=?106) based on final pathologic report. Using the unenhanced images with a threshold of 10 HU, the sensitivity was 45.7?%, and the specificity was 97.1?%. Using the 15-min-washout rate with a threshold of 55?%, the sensitivity was 93.9?%, and the specificity was 95.8?%.

Conclusions

Regardless of various CT machines and protocols, a washout rate of 15-min-delayed CT was most useful in the diagnosis of adrenal adenomas due to the early inflow and outflow of contrast media in the tissues of adrenal adenomas.     

Unexpected double-primary aortoenteric fistula resulting in massive bleeding after induction of anesthesia

We report a case of a patient with a double-primary aortoenteric fistula with an abdominal aortic aneurysm. A 75-year-old man was taken to the operating room for the repair of an abdominal aortic aneurysm and a suspected aortoenteric fistula between the aorta and sigmoid colon. Sudden onset of massive bleeding through the nasogastric tube occurred after the induction of anesthesia. Surgical exploration confirmed an unexpected aortoduodenal fistula. Primary aortoenteric fistula is extremely rare and difficult to diagnose, and may cause fatal bleeding. The possibility of the presence of aortoenteric fistula, including multiple types, should be considered in the anesthetic management of abdominal aortic aneurysm.     

Comparison of anatomic ACL reconstruction between selective bundle reconstruction and double-bundle reconstruction

Purpose

The objective of this study was to compare the clinical and radiologic results of preserved ligament remnants in the selective bundle anterior cruciate ligament (ACL) reconstruction and totally sacrificed ligament remnant in the double-bundle ACL reconstruction in order to confirm the evidence of selective bundle reconstruction.

Methods

This retrospective comparative study was conducted for comparison between preserved ligament remnants in the selective bundle ACL reconstruction and totally sacrificed ligament remnant in the double-bundle ACL reconstruction. From 2008 to 2010, 16 patients (group I) underwent selective bundle ACL reconstruction and 30 patients (group II) underwent double-bundle ACL reconstruction. Clinical, stability and radiologic results (tunnel locations of femoral tunnels using 3-D computed tomography and graft signal intensity using magnetic resonance imaging) were compared.

Results

In comparison with functional results, no statistical differences in the Lysholm, Tegner and International Knee Documentation Committee scores were observed between the two groups (n.s.). In comparison with stability results between the two groups, no statistical differences were observed in the Lachman, pivot shift and anterior drawer stress tests using a Telos^® device at 30° and 90° flexed positions (n.s.). In evaluation of the femoral tunnel location, no statistical significant differences in the tunnel position were observed between the groups (n.s.). No statistically significant differences in signal intensity were observed between the two groups (n.s.).

Conclusions

Compared to the double-bundle ACL reconstruction, selective bundle ACL reconstruction produced comparable clinical and radiologic results. Selective bundle ACL reconstruction could be performed instead of double-bundle ACL reconstruction if some intact bundle exists.

Level of evidence

Comparative study, Level III.     

Two-stage total knee arthroplasty for non-salvageable septic arthritis in diabetes mellitus patients

Pyogenic knee arthritis in a patient with advanced osteoarthritis is a serious medical problem. We have performed arthroscopic debridement in 136 patients with pyogenic knee arthritis from January 1999 to December 2001. Five of these patients were diabetic, they did not respond to the standard treatment protocol and they continued to have infection. For these patients, we performed open arthrotomy, with implantation of antibiotic cement as a spacer, and staged total knee arthroplasty. The clinical results were evaluated using the Hospital for Special Surgery (HSS) scoring system. At an average follow-up of 38 months (range: 29 to 46), the average pain score was 83 and the functional score was 73 with no patient having recurrence of the infection. This study shows that just as a 2-stage revision is now done for infected total knee arthroplasty, primary uncontrolled infected knees may be treated by a 2-stage arthroplasty as well.     

Alveolar soft part sarcoma: MR and angiographic findings

Objective. To present the MR and angiographic findings of alveolar soft part sarcoma (ASPS). Design and patients. MR examinations (12 tumors of 10 patients) of ASPS performed at multiple hospitals were retrospectively reviewed. The tumors were found in the thigh (n=4), lower leg (n=4), femur (n=2, local metastasis), scalp (n=1) and arm (n=1). The MR signal characteristics including signal intensity, homogeneity and signal void of lesions and bony invasion including direct invasion or local metastasis were evaluated. Angiographic findings (n=4) and post-embolotherapy follow-up MR imaging (n=2) findings were also assessed. Results. Local bony metastasis was found in two cases. Seven tumors showed heterogeneous high signal intensity on T1- and T2-weighted images with good enhancement. One tumor had a very high signal on T1-weighted images. Eight tumors (67%) showed numerous signal voids in or near the tumors. All four angiographic studies showed numerous enlarged vessels, arteriovenous shunts and delayed washout. Two cases mimicked arteriovenous malformations on angiographic studies but MR images demonstrated solid soft tissue components as well as tortuous vessels. Conclusions. High signal on T1-weighted image and numerous signal voids are highly suggestive of ASPS, although they are not universal as has been suggested and arteriovenous malformation should be included in the differential diagnosis. Local bony metastases in ASPS were seen in two cases and should be carefully investigated. Received: 12 April 2000 Revision requested: 27 June 2000, 8 August 2000 Revision received: 2 August 2000, 21 August 2000 Accepted: 22 August 2000     

Large-Scale Proteomics and Phosphoproteomics of Urinary Exosomes

Normal human urine contains large numbers of exosomes, which are 40- to 100-nm vesicles that originate as the internal vesicles in multivesicular bodies from every renal epithelial cell type facing the urinary space. Here, we used LC-MS/MS to profile the proteome of human urinary exosomes. Overall, the analysis identified 1132 proteins unambiguously, including 177 that are represented on the Online Mendelian Inheritance in Man database of disease-related genes, suggesting that exosome analysis is a potential approach to discover urinary biomarkers. We extended the proteomic analysis to phosphoproteomic profiling using neutral loss scanning, and this yielded multiple novel phosphorylation sites, including serine-811 in the thiazide-sensitive Na-Cl co-transporter, NCC. To demonstrate the potential use of exosome analysis to identify a genetic renal disease, we carried out immunoblotting of exosomes from urine samples of patients with a clinical diagnosis of Bartter syndrome type I, showing an absence of the sodium-potassium-chloride co-transporter 2, NKCC2. The proteomic data are publicly accessible at http://dir.nhlbi.nih.gov/papers/lkem/exosome/.Urinary exosomes are small extracellular vesicles (<100 nm in diameter) that originate from the internal vesicles of multivesicular bodies (MVB) in renal epithelial cells, including glomerular podocytes, renal tubule cells, and the cells lining the urinary drainage system.¹ Exosomes are released into the urine when the outer membrane of the MVB fuses with the apical plasma membrane of the epithelial cell.Exosomes can be recovered from the urine by differential centrifugation as a low-density membrane fraction. Exosome isolation can result in marked enrichment of low-abundance urinary proteins that have potential pathophysiologic significance. As a consequence, we and others have been working to define optimal conditions for their isolation and purification as a prelude to their use in biomarker discovery studies.^1–3In this study, we thoroughly expanded the known proteome of human urinary exosomes by using a highly sensitive LC-MS/MS system, improved software for identification of peptide ions and a more elaborate data analysis strategy than in our previous study. In addition, we used a neutral loss scanning approach⁴ to investigate the phosphoproteome of human urinary exosomes. The study identified 1412 proteins including 14 phosphoproteins in human urinary exosomes. Overall, there are 177 proteins that are associated with diseases as judged by their presence on the Online Mendelian Inheritance in Man (OMIM) database, 34 of which are known to be associated with renal diseases. The potential clinical usefulness of urinary exosomes was demonstrated using the well-defined renal tubulopathy, Bartter syndrome type I, as an example. The rich information from the proteomic analysis also provides further insight into the biogenesis of urinary exosomes.     

US screening for detection of nonpalpable locoregional recurrence after mastectomy

Purpose

To assess the value of screening ultrasonography (US) in the detection of nonpalpable locoregional recurrence following mastectomy for breast cancer and to describe the US appearances of occult recurrent cancers.

Materials and methods

During a 36-month period, 1180 consecutive US screenings were performed for mastectomy sites and ipsilateral axillary fossae in 468 asymptomatic women who had undergone mastectomy for breast cancer. All US results were divided into three groups: negative findings, probably benign nodules, and suspicious for malignant nodules. The final diagnoses were based on pathology results and clinical or sonographic follow-up for more than 12 months. The diagnostic performance of US for detecting nonpalpable locoregional recurrence was assessed. The US appearances of occult recurrent cancers were retrospectively reviewed.

Results

Of the 468 patients assessed, 19 (4.1%) showed “suspicious for malignant nodules”; of these lesions, 10 were malignant. One false-negative case was identified. The sensitivity and specificity were 90.9% and 98.0%, respectively. A biopsy positive predictive value of 52.6% was observed. Cancer detection rates were 2.1% with US screenings of mastectomy sites and ipsilateral axillary fossae. The common US features of occult recurrences at the mastectomy sites were irregular shaped, not-circumscribed marginated, and hypoechoic masses with intratumoral vascularities. The most common location was within the deep muscle layer.

Conclusion

Although locoregional recurrence infrequently occurs after mastectomy for breast cancer, screening US enables detection of nonpalpable cancer before it can be detected by clinical examination. Routine follow-up US can be advocated for early detection of nonpalpable locoregional recurrent cancer.