Immunolocalization and expression of lubricin in the bilaminar zone of the human temporomandibular joint disc

Lubricin, which is a boundary joint lubricant, was investigated immunohistochemically in the bilaminar zone (BZ) of the human temporomandibular joint (TMJ), without any degenerative changes. Immunohistochemistry for lubricin detection was carried out on 33 TMJ discs obtained from 17 cadavers. Sections were incubated with diluted rabbit polyclonal anti-lubricin antibody and scored according to the percentage of lubricin immunopositive cells. Three different TMJ disc tissue compartments were analyzed, namely: the upper lamina, the inferior lamina and the loose connective tissue in the space between the laminae. The Mann-Whitney U test was used to compare protein expression (lubricin) among disc specimens’ regions. Staining was noted within the TMJ disc cell populations in every disc tissue sample, with almost every cell immunolabeled by the lubricin antibody. The number of disc cells immunolabeled was almost the same in the 3 bilaminar zone regions. Positive extracellular matrix staining was also seen. The results of the present study suggest that lubricin is expressed in the TMJ disc bilaminar zone. Lubricin may have a role in normal disc posterior attachment physiology through the prevention of cellular adhesion as well as providing lubrication during normal bilaminar zone function.     

Challenges of establishing the correct diagnosis of outbreaks of acute febrile illnesses in Africa: the case of a likely Brucella outbreak among nomadic pastoralists, northeast Kenya, March-July 2005

An outbreak of acute febrile illness was reported among Somali pastoralists in remote, arid Northeast Kenya, where drinking raw milk is common. Blood specimens from 12 patients, collected mostly in the late convalescent phase, were tested for viral, bacterial, and parasitic pathogens. All were negative for viral and typhoid serology. Nine patients had Brucella antibodies present by at least one of the tests, four of whom had evidence suggestive of acute infection by the reference serologic microscopic agglutination test. Three patients were positive for leptospiral antibody by immunoglobulin M enzyme-linked immunosorbent assay, and two were positive for malaria. Although sensitive and specific point-of-care testing methods will improve diagnosis of acute febrile illness in developing countries, challenges of interpretation still remain when the outbreaks are remote, specimens collected too late, and positive results for multiple diseases are obtained. Better diagnostics and tools that can decipher overlapping signs and symptoms in such settings are needed.     

Objective measures of renal mass anatomic complexity predict rates of major complications following partial nephrectomy

Background

The association between tumor complexity and postoperative complications after partial nephrectomy (PN) has not been well characterized.

Objective

We evaluated whether increasing renal tumor complexity, quantitated by nephrometry score (NS), is associated with increased complication rates following PN using the Clavien-Dindo classification system (CCS).

Design, setting, and participants

We queried our prospectively maintained kidney cancer database for patients undergoing PN from 2007 to 2010 for whom NS was available.

Interventions

All patients underwent PN.

Measurements

Tumors were categorized into low- (NS: 4-6), moderate- (NS: 7-9), and high-complexity (NS: 10-12) lesions. Complication rates within 30 d were graded (CCS: I-5), stratified as minor (CCS: I or 2) or major (CCS: 3-5), and compared between groups.

Results and limitations

A total of 390 patients (mean age: 58.0 ± 11.9 yr; 66.9% male) undergoing PN (44.6% open, 55.4% robotic) for low- (28%), moderate- (55.6%), and high-complexity (16.4%) tumors (mean tumor size: 3.74 ± 2.4 cm; median: 3.2 cm) from 2007 to 2010 were identified. Tumor size, estimated blood loss, and ischemia time all significantly differed (p < 0.0001) between groups; patient age, body mass index (BMI), and operative time were comparable. When stratified by CCS, minor and major complication rates for all patients were 26.7% and 11.5%, respectively. Minor complication rates were comparable (26.6 vs 24.9 vs 32.8%; p = 0.45), whereas major complication rates differed (6.4 vs 11.1 vs 21.9%; p = 0.009) among tumor complexity groups. Controlling for age, gender, BMI, type of surgical approach, operative duration, and tumor complexity, prolonged operative time (odds ratio [OR]: 1.01; confidence interval [CI], 1.0-1.02) and high tumor complexity (OR: 5.4; CI, 1.2-24.2) were associated with the postoperative development of a major complication. Lack of external validation is a limitation of this study.

Conclusions

Increasing tumor complexity is associated with the development of major complications after PN. This association should be validated externally and integrated into the decision-making process when counseling patients with complex renal tumors.     

Percutaneous vs surgical cryoablation of the small renal mass: is efficacy compromised?

Study Type – Therapy (systematic review)
Level of Evidence 1b What’s known on the subject? and What does the study add? Cryoablation of the small renal mass is one amongst many minimally invasive approaches to treatment. Cryoablation can be performed both surgically and percutaneously; direct comparison of the two approaches has proven the percutaneous approach to be cheaper, less morbid, result in shorter procedure times, and shorter hospital stays, all with equal efficacy. Our study examines the decision as well as reporting process for the selection of treatment approach to determine if patients are being unnecessarily exposed to more invasive therapeutic options.

OBJECTIVE

• ? To review and analyse the cumulative literature to compare surgical and percutaneous cryoablation of small renal masses (SRMs).

METHODS

• ? A MEDLINE search was performed (1966 to February 2010) of the published literature in which cryoablation was used as therapy for localized renal masses.
• ? Residual disease was defined as persistent enhancement on the first post‐ablation imaging study, while recurrent disease was defined as enhancement after an initially negative postoperative imaging study, consistent with the consensus definition by the Working Group on Image‐Guided Tumor Ablation.
• ? Data were collated and analysed using the two‐sample Mann–Whitney test and random‐effects Poisson regression, where appropriate.

RESULTS

• ? In all, 42 studies, representing 1447 lesions treated by surgical (n= 28) or percutaneous (n= 14) cryoablation were pooled and analysed.
• ? No significant differences were detected between approaches regarding patient age (median 67 vs 66 years, P= 0.55), tumour size (median 2.6 vs 2.7 cm, P= 0.24),or duration of follow‐up (median 14.9 vs 13.3 months, P= 0.40).
• ? Differences in rates of unknown pathology also failed to reach statistical significance (14 vs 21%, P= 0.76). The difference in the rate of residual tumour was not statistically different (0.033 vs 0.046, P= 0.25), nor was the rate of recurrent tumour (0.008 vs 0.009, P= 0.44).
• ? The reported rate of metastases was negligible in both groups, precluding statistical analysis.

CONCLUSIONS

• ? Cryoablation has shown acceptable short‐term oncological results as a viable strategy for SRMs.
• ? Analysis of the cumulative literature to date shows that surgical and percutaneous cryoablation have similar oncological outcomes.

     

Clinicopathological outcomes after radical cystectomy for clinical T2 urothelial carcinoma: further evidence to support the use of neoadjuvant chemotherapy

Study Type – Therapy (case series)
Level of Evidence 4 What’s known on the subject? and What does the study add? Systemic chemotherapy for muscle‐invasive bladder cancer is underutilized. Currently, debate centers on whether patients should be given neoadjuvant chemotherapy or be given chemotherapy after surgery, depending on the pathology of the specimen. In this paper, we found that greater than 73% of patients had evidence of bladder cancer that was locally advanced, a criteria that would designate these patients for adjuvant chemotherapy. Using this evidence and the knowledge that neoadjuvant chemotherapy confers a survival advantage, we argue that neoadjuvant chemotherapy should be the standard of care.

OBJECTIVE

To evaluate the clinicopathological outcomes for patients with clinical T2 (cT2) urothelial carcinoma treated with radical cystectomy (RC) without neoadjuvant chemotherapy (NC).

PATIENTS AND METHODS

We identified 212 patients with cT2 tumours who underwent RC at our institution without NC. Pathological assessment of RC specimens was correlated with clinical stage. The impact of various clinicopathological factors on the outcome of patients with cT2 disease was analysed.

RESULTS

In total, 153/212 (73.2%) patients with cT2 bladder cancer had either pT3/T4 or pN+ tumours at RC. Moreover, only 58/153 (37.9%) of these patients received adjuvant chemotherapy. The median follow‐up was 28 (months 0.6–107.5) (range). The 5‐year recurrence‐free survival and cancer‐specific survival (CSS) was 56.5% and 59.5%, respectively. On multivariate analysis, increasing age (hazard ratio [HR] 1.04; P= 0.04), advanced pathological stage (HR 1.83; P= 0.02), and positive lymph nodes (HR 3.72; P= 0.001) were adversely associated with CSS, while receipt of adjuvant chemotherapy was protective of disease‐specific mortality (HR 0.45; P= 0.04).

CONCLUSIONS

Pathological upstaging is prevalent and survival remains modest in patients with cT2 tumours treated with RC without NC. Unfortunately, only 40% of patients that had locally advanced and/or regionally metastatic disease received adjuvant treatment. These data further support the value of NC for patients with muscle‐invasive bladder cancer, even in those with apparent clinically organ‐confined tumours.     

Relation of C-reactive protein to oxidative stress and to endothelial activation in essential hypertension

BACKGROUND: C-reactive protein (CRP) predicts cardiovascular outcome. Oxidative stress is considered to be involved in endothelial alteration. We hypothesized that in essential hypertension (EH), oxidative stress, as measured by 8-iso-prostaglandin-F(2alpha) (8-iso-PGF(2alpha)), should be associated with increased CRP and endothelial activation, as evaluated by soluble intercellular adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1) plasma levels. METHODS: In 83 subjects with mild EH and in 50 healthy control subjects we measured, in basal conditions, plasma levels of hs-CRP, 8-iso-PGF(2alpha), ICAM-1 and VCAM-1, and tumor necrosis factor-alpha (TNF-alpha). RESULTS: Subjects with EH had higher levels of 8-iso-PGF(2alpha) (P < .0001), CRP (P < .001), ICAM-1 and VCAM-1 (P < .001), and TNF-alpha (P < .001) than did control subjects. We divided successively EH according to CRP values (<1, 1-3, >3 mg/L), and we observed increasing and significantly different levels of the endothelial parameters and of TNF-alpha along with increasing CRP. Linear analysis of correlation pointed out significant correlation of CRP with 8-iso-PGF(2alpha) (r = 0.730, P < .001), ICAM-1 and VCAM-1 (r = 0.642 and 0.468, P < .001 respectively), and TNF-alpha (r = 0.609, P < .001). Multiple regression analysis using CRP as a dependent variable confirmed the relationship of CRP with systolic blood pressure (beta 0.216, P = 0.039) and with 8-iso-PGF(2alpha) (beta 0.602, P = .0001). CONCLUSIONS: Our data demonstrate that in EH, inflammatory molecules such as CRP and TNF-alpha are increased and related to both oxidative stress and endothelial activation.