Patellar meniscus in total knee arthroplasty

Twenty-four clinically successful, autopsy retrieved porous-coated anatomic total knee arthroplasty (TKA) specimens were evaluated to determine the structure and function of the patellar meniscus. Mean implant duration was 76 months (range: 11-135 months). Histological examination showed the patellar meniscus to be composed of dense fibrous tissue with scattered regions of chronic granulomatous response to polyethylene debris. Patellar wear and polyethylene exposed patellar surface area were correlated with implant duration (r = 0.47, P = .03; r = 0.52, P = .06). Postoperative patellar tilt was also associated with patellar component wear (r = 0.64, P = .03). No other clinical measures were significantly associated with patellar wear or exposed surface area. Additional research is needed to determine what role, if any, the patellar meniscus plays in TKA outcomes.     

Gastric fluid bile concentrations and risk of Barrett's esophagus

Patients with Barrett's esophagus are at high risk of progression to adenocarcinoma. A growing, but conflicting body of evidence implicates bile reflux as a contributor to Barrett's esophagus. To investigate whether duodenogastric reflux was associated with an increased risk of Barrett's esophagus, a case-control study of incident Barrett's esophagus was performed. Cases (n=72) were identified by new histologically-confirmed diagnosis of specialized intestinal metaplasia (indicative of Barrett's esophagus) following upper endoscopy for refractory gastroesophageal reflux between October 1997 and September 2000. Cases were compared to gastroesophageal reflux patients without specialized intestinal metaplasia (controls; n=72). There was no difference in total bile acid concentrations between cases and controls. Risk of Barrett's esophagus did not significantly vary with increasing concentrations of total or free bile acids, respectively (OR 0.35 (95% CI 0.12, 1.02) and 0.60 (95% CI 0.22, 1.66)). Low gastric fluid pH (toxic range 3-5), was associated with a non-significant increase in the risk of Barrett's esophagus. In conclusion, no significant association between Barrett's esophagus and total or free bile acids in gastric refluxate was found. Patients with low gastric fluid pH (3-5) may represent a subset of patients at high risk of developing Barrett's esophagus.     

What predicts attrition in second step medication treatments for depression?: a STAR*D Report

Attrition rates are high during treatment for major depressive disorder (MDD), and patients who drop out are less likely to reach remission. This report evaluates the incidence, timing, and predictors of attrition during second-step medication treatment. Outpatients in the multisite Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study receiving a medication augmentation (n=563) or medication switch (n=723) for non-psychotic MDD after an unsatisfactory outcome with citalopram were evaluated to determine attrition rates and pretreatment sociodemographic or clinical predictors of attrition. Twenty percent of participants receiving a medication augmentation and 27% receiving a medication switch dropped out before 12 wk in the second treatment step. Remission rates were lower for dropouts [7% vs. 43% (medication augmentation); 12% vs. 31% (medication switch)]. For medication augmentation, Black and other non-Caucasian races, Hispanic ethnicity, younger age, family history of drug abuse, concurrent drug abuse, sociodemographic disadvantage, less symptom improvement with initial citalopram treatment, and greater symptom severity when beginning augmentation were associated with attrition. For medication switch, Black and other non-Caucasian races, younger age, more melancholic features, and lower exit doses but more severe side-effects with citalopram treatment were associated with attrition. Minority status, younger age, and greater difficulty with the first treatment step are risk factors for attrition in the second treatment step. Focus on patients with attrition risk factors for medication augmentation or switch strategies may enhance retention and improve outcomes.     

Stimulation of ankle cartilage: other emerging technologies (cellular, electricomagnetic, etc.)

Advances in understanding age-related changes in articular cartilage, joint homeostasis, the natural healing process after cartilage injury, and improved standards for evaluation of a joint surface made the ultimate goal of cartilage repair a possibility. New strategies for enhancement of articular cartilages' limited healing potential and biologic regeneration include advances in tissue engineering and the use of electromagnetic fields. This article reviews developments in basic science and clinical research made with these emerging technologies concerning treatment of articular cartilage defects and treatment of osteoarthritis of the ankle.     

Reoperative sentinel lymph node biopsy in patients with locally recurrent breast cancer

BACKGROUND: Sentinel lymph node biopsy (SLNB) is considered a standard of care in the staging of breast cancer. The objective was to examine our experience with reoperative SLNB. METHODS: We identified 19 patients in our breast cancer database who had a SLNB in the reoperative setting. All 19 patients had undergone previous breast-conserving surgery with either an axillary lymph node dissection or an SLNB. The reoperative sentinel lymph node (SLN) was identified using blue dye, radioisotope, or both. RESULTS: The SLN was identified in 84% of the reoperative cases. Of these successful cases, both blue dye and radioisotope were used in five cases, and radioisotope alone was used in 11 cases. Radioisotope identified the SLN in the 100% of successful SLNB cases (P = .0003). There were 3 unsuccessful cases in which blue dye and radioisotope failed to identify the sentinel node. CONCLUSIONS: Reoperative SLNB after previous axillary surgery is technically feasible.     

Development of a Murine Mycobacterial Growth Inhibition Assay for Evaluating Vaccines against Mycobacterium tuberculosis

The development and characterization of new tuberculosis (TB) vaccines has been impeded by the lack of reproducible and reliable in vitro assays for measuring vaccine activity. In this study, we developed a murine in vitro mycobacterial growth inhibition assay for evaluating TB vaccines that directly assesses the capacity of immune splenocytes to control the growth of Mycobacterium tuberculosis within infected macrophages. Using this in vitro assay, protective immune responses induced by immunization with five different types of TB vaccine preparations (Mycobacterium bovis BCG, an attenuated M. tuberculosis mutant strain, a DNA vaccine, a modified vaccinia virus strain Ankara [MVA] construct expressing four TB antigens, and a TB fusion protein formulated in adjuvant) can be detected. Importantly, the levels of vaccine-induced mycobacterial growth-inhibitory responses seen in vitro after 1 week of coculture correlated with the protective immune responses detected in vivo at 28 days postchallenge in a mouse model of pulmonary tuberculosis. In addition, similar patterns of cytokine expression were evoked at day 7 of the in vitro culture by immune splenocytes taken from animals immunized with the different TB vaccines. Among the consistently upregulated cytokines detected in the immune cocultures are gamma interferon, growth differentiation factor 15, interleukin-21 (IL-21), IL-27, and tumor necrosis factor alpha. Overall, we have developed an in vitro functional assay that may be useful for screening and comparing new TB vaccine preparations, investigating vaccine-induced protective mechanisms, and assessing manufacturing issues, including product potency and stability.The tuberculosis (TB) epidemic is a global public health tragedy that is being fueled by the spread of human immunodeficiency virus/AIDS and the increasing incidence of multiple-drug-resistant Mycobacterium tuberculosis strains. Annually, about 2 million people worldwide die from tuberculosis and 8 to 9 million new cases of this disease are reported (34). Although the current TB vaccine, Mycobacterium bovis BCG, has been widely used for decades, its effectiveness has been shown to be highly variable in well-controlled clinical trials (5). While immunization with BCG is effective against severe childhood disease, BCG does not adequately protect against the most prevalent form of the disease, adult pulmonary tuberculosis (13). Vaccinated individuals who become infected with TB are susceptible to disease progression when the BCG-induced immune responses are suppressed or wane with time (32). Clearly, to curb the global TB epidemic, more effective immunization strategies must be generated and evaluated.The development of new vaccines against TB has been hindered by our limited understanding of the mechanisms of protective immunity against M. tuberculosis. While it is known that acquired cellular immune responses are critical for controlling tuberculosis infections, the cell subsets that confer antituberculosis protective immunity have not been adequately defined (14). In addition, the immune mechanisms that are responsible for inhibiting the intracellular growth of M. tuberculosis have not been fully delineated and the surrogate biomarkers of this growth inhibition remain unknown. Because it is difficult to study the multiple components of the immune system and their numerous interactions in vivo, the development of an in vitro system which models the in vivo immune responses should facilitate the identification of antituberculosis protective immune mechanisms. The availability of a relevant in vitro assay should allow a more direct study of the mediators of protective immunity against M. tuberculosis in a controlled system. Although in vitro mycobacterial growth inhibition assays for human cells have been developed and are being characterized for their capacity to detect vaccine-induced immunogenicity in human clinical trials, the development and assessment of preclinical assays to measure vaccine-induced activity against M. tuberculosis has thus far been limited (4, 6, 16, 18, 30, 35).To accelerate TB vaccine development and investigations of protective immune mechanisms, we initiated studies aimed at developing a murine in vitro functional assay for evaluating the protective activity of TB vaccines. For this assay, antituberculosis protection was evaluated by targeting an important end point, the control of M. tuberculosis growth within its primary host cell, the macrophage. By assessing the immune-mediated inhibition of mycobacterial growth, we hypothesized that our results would correlate more directly with in vivo protection than the measurement of other immune responses, including cytokine expression. In addition to assessing cellular immune mechanisms, a relevant in vivo assay could be useful for screening and comparing new TB vaccine candidates. From a manufacturing viewpoint, a standardized in vitro functional assay could also be adapted to measure vaccine potency, lot-to-lot production consistency, and vaccine stability.Here we describe our initial results from the characterization of a murine in vitro functional assay for assessing the activity of TB vaccines. We show that vaccine-induced protection seen in vitro for five different TB vaccines correlates with the antituberculosis protective immunity detected in a mouse model of pulmonary TB. Also, we establish an in vitro profile of cytokine expression which is associated with the activity of BCG vaccine and demonstrate that similar in vitro cytokine responses were detected for the four other types of TB vaccines that were tested in this study.     

Cystic hygroma

Cystic hygroma (CH) is a benign, developmental condition of unknown etiology. 90% of the cases are present by age 2. CH represents malformed lymphatics that fail to communicate with larger veins and, therefore, they collect lymph. It is a type of lymphangioma. The clinical presentation is one of a painless, soft mass that reaches a giant size and can lead to the death of the infant. The diagnosis is done with CT scan and biopsy. We report a severe case of CH and describe the difficult surgical treatment, despite the benign nature of the lesion.