Tendon Graft—Ulna Fixation in Distal Radio-Ulnar Joint Stabilisation; Biomechanical Comparison of Three Graft-Bone Fixation Methods

A common distal radio-ulnar joint (DRUJ) stabilisation procedure uses a tendon graft running from the lip of the radial sigmoid notch to the ulnar fovea and through a bony tunnel to the ulnar shaft, before being wrapped round the distal ulna and sutured to itself. Such graft fixation can be challenging and requires a considerable tendon length. The graft length could be reduced by fixing the graft to the ulna using a bone anchor or interference screw. The aim of this study was to compare the strength of three distal ulna graft fixation methods (tendon wrapping and suturing, bone anchor and interference screw). Four human cadaveric ulnae were used. A tendon strip was run through a tunnel in the distal ulna and secured by: (1) wrapping round the shaft and suturing it to itself, (2) a bone anchor and (3) an interference screw in the bone tunnel. Load to failure was determined using a custom-made apparatus and an Instron machine. Maximum failure load was highest for the bone anchor fixation (99.3 ± 23.7 N) followed by the suturing (96.2 ± 12.1 N), and the interference screw fixation (46.9 ± 5.6 N). There was no significant difference between the tendon suturing and bone anchor methods, but the tendon suturing was statistically significantly higher compared to the interference screw (P = 0.028). In performing anatomical stabilisation of the DRUJ fixation of the tendon graft to the distal ulna with a bone anchor provides the most secure fixation. This may make the stabilisation technique less demanding and require a smaller tendon graft.     

Claudin 18 is a novel negative regulator of bone resorption and osteoclast differentiation

Claudin 18 (Cldn-18) belongs to a large family of transmembrane proteins that are important components of tight junction strands. Although several claudin members are expressed in bone, the functional role for any claudin member in bone is unknown. Here we demonstrate that disruption of Cldn-18 in mice markedly decreased total body bone mineral density, trabecular bone volume, and cortical thickness in Cldn-18(-/-) mice. Histomorphometric studies revealed that bone resorption parameters were increased significantly in Cldn-18(-/-) mice without changes in bone formation. Serum levels of tartrate-resistant acid phosphatase 5b (TRAP5b) and mRNA expression levels of osteoclast specific markers and signaling molecules were also increased. Loss of Cldn-18 further exacerbated calcium deficiency induced bone loss by influencing bone resorption, thereby resulting in mechanically weaker bone. In vitro studies with bone marrow macrophages revealed Cldn-18 disruption markedly enhanced receptor activator of NF-κB ligand (RANKL)-induced osteoclast differentiation but not macrophage colony-stimulating factor (MCSF)-induced bone marrow macrophage (BMM) proliferation. Consistent with a direct role for Cldn-18 in regulating osteoclast differentiation, overexpression of wild type but not PDZ binding motif deleted Cldn-18 inhibited RANKL-induced osteoclast differentiation. Furthermore, our findings indicate that Cldn-18 interacts with Zonula occludens 2 (ZO-2) to modulate RANKL signaling in osteoclasts. In conclusion, we demonstrate that Cldn-18 is a novel negative regulator of bone resorption and osteoclast differentiation.     

Characteristics and Outcomes of Sentinel Node–Positive Breast Cancer Patients after Total Mastectomy without Axillary-Specific Treatment

Purpose

Regional failure rates are low in patients with a positive sentinel lymph node biopsy (SLNB) who undergo breast-conserving therapy without axillary lymph node dissection (ALND). The applicability of these findings to total mastectomy (TM) patients is not established. Our aims were to evaluate the characteristics and outcomes of SLNB-positive TM patients who did not receive axillary-specific treatment and to compare them to similar patients who underwent breast-conserving surgery (BCS).

Methods

A total of 535 patients with early-stage breast cancer who underwent definitive breast surgery (210 TM, 325 BCS), had a positive SLNB and did not receive ALND between 1997 and 2009 were identified from an institutional database. Characteristics and outcomes were compared between the TM and BCS groups.

Results

Most patients had stage I to IIA, estrogen receptor?Cpositive, progesterone receptor?Cpositive, Her2-negative invasive ductal carcinoma, with minimal nodal disease. Compared to the BCS group, TM patients were younger, had larger tumors, had higher nomogram scores predicting additional axillary disease and were more likely to receive chemotherapy. Ninety-four percent of the BCS cohort and 5?% of the TM cohort received adjuvant radiotherapy. At a median follow-up of 57.8?months, the 4-year local, regional and distant failure rates were 1.7, 1.2 and 0.7?% in the TM group and 1.4, 1.0 and 3.7?% in the BCS group. The 4-year disease-free and overall survival rates were 94.8 and 97.8?% in the TM group and 90.1 and 92.6?% in the BCS group.

Conclusions

Early-stage breast cancer patients with minimal sentinel node disease experience excellent outcomes without ALND, whether they undergo BCS or TM.     

Glucose-induced oxidative stress in mesangial cells

BACKGROUND: Hyperglycemia is a well-recognized pathogenic factor of long-term complications in diabetes mellitus. Hyperglycemia not only generates reactive oxygen species but also attenuates antioxidant mechanisms creating a state of oxidative stress. METHODS: Porcine mesangial cells were cultured in high glucose (HG) for ten days to investigate the effects on the antioxidant defenses of the cell. RESULTS: Mesangial cells cultured in HG conditions had significantly reduced levels of glutathione (GSH) compared with those grown in normal glucose (NG). The reduced GSH levels were accompanied by decreased gene expression of both subunits of gamma-glutamylcysteine synthetase (gamma-GCS), the rate-limiting enzyme in de novo synthesis of GSH. Elevated levels of intracellular malondialdehyde (MDA) were found in cells exposed to HG conditions. HG also caused elevated mRNA levels of the antioxidant enzymes CuZn superoxide dismutase (SOD) and MnSOD. These changes were accompanied by increased mRNA levels of extracellular matrix proteins (ECM), fibronectin (FN) and collagen IV (CIV). Addition of antioxidants to high glucose caused a significant reversal of FN and CIV gene expression; alpha-lipoic acid also up-regulated gamma-GCS gene expression and restored intracellular GSH and MDA levels. CONCLUSIONS: The results demonstrate the existence of glucose-induced oxidative stress in mesangial cells as evidenced by elevated MDA and decreased GSH levels. The decreased levels of GSH are as a result of decreased mRNA expression of gamma-GCS within the cell. Antioxidants caused a significant reversal of FN and CIV gene expression, suggesting an etiological link between oxidative stress and increased ECM protein synthesis.     

Glycoprotein IIb/IIIa receptor inhibitor attenuates platelet aggregation induced by thromboxane A2 during in vitro nonpulsatile ventricular assist circulation

A recent development in antithrombotic research allows the inhibition of platelet aggregation via protection of the glycoprotein IIb/IIIa receptor on the platelet membrane. We hypothesized that a GP IIb/IIIa receptor inhibitor would inhibit thromboxane-induced platelet aggregation during circulation in our in vitro ventricular assist device (VAD) circuit and preserve long-term platelet function. Twenty-one in vitro nonpulsatile centrifugal VAD circuits were simulated for 4 days using 450 ml of fresh human whole blood with or without glycoprotein IIb/IIIa receptor inhibitor (tirofiban). Platelet aggregation and degranulation were measured in whole blood induced by ristocetin, collagen, ADP, and thromboxane A2 (TXA2). The tirofiban-treated group preserved the platelet count and tended to exert these beneficial effects by inhibiting pathologic platelet aggregation induced by TXA2, collagen, and ADP as well as degranulation. Tirofiban may be useful in preserving platelet number and function during clinical VAD use.     

Epididymectomy is an effective treatment for scrotal pain after vasectomy

OBJECTIVE: To investigate the efficacy of epididymectomy in patients with significant scrotal pain after vasectomy. PATIENT AND METHODS: Sixteen patients were identified retrospectively to have undergone epididymectomy for pain after vasectomy; 19 epididymectomies were performed (three bilateral and 13 unilateral). Details from the preoperative investigations, histological examination and follow-up of symptoms were analysed and correlated. Outcomes were initially assessed at the routine outpatient clinic review 3 months after surgery and the long-term outcomes were assessed by a telephone interview 3-8 years after epididymectomy (mean 5.5 years). RESULTS: Of the 16 patients, 14 had excellent initial symptomatic benefit from epididymectomy. At 3-8 years afterward, nine of 10 patients interviewed had a sustained improvement of their scrotal pain. The following were indicators of a poor outcome: atypical symptoms including testicular or groin pain; erectile dysfunction and normal appearance of the epididymis on ultrasonography. Patients with bilateral scrotal pain can have a good outcome after epididymectomy. CONCLUSION: Epididymectomy in well-selected patients is a reliable and effective treatment for pain after vasectomy.     

Cystic fibrosis and the phenotypic expression of autosomal dominant polycystic kidney disease

Recent experiments in cultured cyst epithelial cells from kidneys of patients with autosomal dominant polycystic kidney disease (ADPKD) have shown that the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) is present in the apical surface of these cells and mediates chloride (Cl-) and fluid secretion in vitro. To determine whether the presence of CF with the expression of mutated CFTR proteins modifies cyst formation in ADPKD, we studied a large family with both inherited diseases. ADPKD in this family is linked to PKD1. The family is composed of 26 members; 11 members with ADPKD, 4 members with CF, and 2 members with both diseases. Renal volumes measured by computerized tomography (CT), calculated creatinine clearances, and other clinical parameters in the family members with ADPKD and CF were compared with those in the family members with ADPKD alone, as well as to a large population of patients with ADPKD. The patients with CF and ADPKD, but not the CF heterozygote carriers with ADPKD, had less severe polycystic kidney and liver disease, as indicated by normal renal function; smaller renal volume, even when corrected for height and body surface area; and the absence of hypertension and liver cysts. These observations suggest that the coexistence of CF may reduce the severity of ADPKD.     

Results of a clinical care pathway for radical prostatectomy patients in an open hospital - multiphysician system

OBJECTIVES: The object of this study was to evaluate the results of a comprehensive clinical care pathway (CCP) aimed at reducing the length of hospitalization and overall cost for patients undergoing radical prostatectomy in a setting including both academic and private physicians. METHODS: The clinical records of 1,129 consecutive patients who underwent radical prostatectomy by 24 urologists between July 1, 1990, and December 31, 1996, were reviewed. The factors considered were length of stay, morbidity and mortality, readmission rates, and average cost. The CCP was implemented on January 1, 1994. Its scope was to minimize preoperative evaluation, eliminate the preoperative hospital stay, standardize postoperative care and provide intensive patient education. RESULTS: The average length of stay decreased significantly after implementation of the CCP (8.1 vs. 4.9 days, p = 0.0001). In 1990, there was a large difference in length of stay between academic and private physicians (8.3 vs. 12.6 days) (p = 0. 02) but by 1 year after implementation of the CCP there was virtually no difference (4.69 vs. 4.71 days) (p > 0.05). Complication rates were similar before and after implementation of the CCP. Using the average 1993 cost/case as the baseline preCCP figure, the average cost of radical prostatectomy decreased by 16% in 1994 and by 22% in 1995. CONCLUSIONS: It is possible to successfully implement a CCP in a multi-physician system to reduce length of stay and cost of radical prostatectomy without subjecting the patient to a greater risk of complication.     

Epidemiology and pathophysiology of prostate cancer in African-American men

PURPOSE: Along with increasing age and a positive family history subSaharan African ancestry has long been recognized as an important risk factor for prostate cancer. In the United States the incidence of prostate cancer is approximately 60% higher in African-American than in European-American men and the mortality rate from the disease is more than twice as high. The purpose of this review article is to examine specific reports highlighting racial disparity and its possible causes. MATERIALS AND METHODS: The reports chosen for review of this epidemiology and pathophysiology study were included to demonstrate conditions in which racial differences as well as similarities exist in African-American and European-American men. Reports also include autopsy, biological and clinical studies, and early and late stage prostate cancer. RESULTS: From the 1970s to the current statistical analysis of the National Cancer Institute Surveillance, Epidemiology, and End Results program African-American men have continued to have a significant higher incidence and mortality rate than European-American men. Autopsy studies show a similar prevalence of early small subclinical prostate cancers but a higher prevalence of high grade prostatic intraepithelial neoplasia. Clinical studies show a similarity in prostate cancer outcome when pathological stage is organ confined but a worse outcome when disease is locally advanced and metastatic in African-American vs European-American men. There is increasing genetic evidence that suggest that prostate cancer in African-American vs European-American men may be more aggressive, especially in young men. CONCLUSIONS: Improving the outcome in African-American men with prostate cancer requires awareness of the epidemiological patterns of the disease and willingness on the part of physicians to implement targeted study initiatives with end points designed to detect the disease early in this population and begin appropriate management. It is proposed that a multi-institutional study should be done to demonstrate the ability to decrease racial outcome disparity by education, aggressive testing and treatment.