Development of traumatic retinal detachment

Post-traumatic retinal detachment occurs frequently as a late consequence of progressive vitreous changes, especially following penetrating injuries. Occasionally, it develops soon after the trauma, without preceding proliferative vitreoretinopathy, is based on posterior vitreous detachment and morphologically resembles an idiopathic retinal detachment. It is possible that the posterior vitreous detachment in these cases is encouraged by the presence of intravitreal hemorrhage.     

Peripheral proliferative vitreoretinopathy in intermediary uveitis

Certain types of intermediary uveitis are accompanied by proliferative vitreoretinopathy and retinal detachment. As a rule both complications are confined to the fundus periphery; they often occur simultaneously but they are not always related to one another. Exudate plaques and/or neovascularizations at the base of the vitreous are the precursors of peripheral proliferative vitreoretinopathy. Clinical findings and their therapeutic consequences are discussed.     

L-thyroxine increases susceptibility of adult rats to low K+-induced ventricular fibrillation, and sinus rhythm restoration in old rats

Hypokalaemia increases the risk for life-threatening arrhythmias; however, data about interaction with thyroid status are lacking. The aim of this study was to investigate vulnerability of l-thyroxine (T(4))-treated adult and old rats to low K(+)-induced ventricular fibrillation (VF) as well as the ability of the heart to recover sinus rhythm. The experiments were performed on isolated heart preparations using the heart of 4- and 20-month-old female Wistar rats without and with feeding with T(4) 50 microg (100 g day)(-1) over a period of 2 weeks. Perfusion of the isolated heart with oxygenated Krebs-Henseleit solution at constant pressure was followed by perfusion with K(+)-deficient solution until occurrence of VF (< 10 min). After 2 min of sustained VF, the heart was perfused with normal solution for 10 min, during which sinus rhythm was restored. ECG, left ventricular pressure (LVP) and coronary flow were continuously monitored. The results showed that compared with untreated rats, the onset of low K(+)-induced ventricular premature beats was delayed and their number was significantly decreased in both T(4)-treated groups. Nevertheless, VF occurred earlier in T(4)-treated than in non-treated adult rats (6.78 +/- 0.28 vs. 9.59 +/- 0.55 min, P < 0.05), whereas the difference was not significant in aged animals. Furthermore, sinus rhythm appeared earlier in old T(4)-treated rats compared with non-treated rats (7.18 +/- 0.57 vs. 8.94 +/- 0.64 min, P < 0.05), whereas in adult hearts it set in at practically the same time regardless of treatment. In conclusion, our results indicate that administration of a pharmacological dose of T(4) can increase the risk of low K(+)-induced VF in adult but not in old animals; in the latter it even facilitated restoration of sinus rhythm. Moreover, enhanced mechanical function was observed in both adult and old T(4)-treated hearts.     

Time- and concentration-dependent induction of CYP1A1 and CYP1A2 in precision-cut rat liver slices incubated in dynamic organ culture in the presence of 2,3,7,8-tetrachlorodibenzo-p-dioxin

In a previous 24-h study, precision-cut rat liver slices were validated as a useful in vitro model for assessing the dose-related induction of CYP1A1 and CYP1A2 in rat liver following exposure to 2, 3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Further assessment of the utility of this model was accomplished by initially exposing rat liver slices to medium containing TCDD (0.01 nM) for 24 h and incubating the slices up to an additional 72 h in TCDD-free medium. The slices remained viable throughout the incubation period with an intracellular potassium content varying from 45.2 +/- 2.3 micromol/g at 48 h to 50.0 +/- 1.6 micromol/g at 72 h. In TCDD-exposed slices, CYP1A1 protein and its respective enzymatic activity, the O-deethylation of ethoxyresorufin (EROD), significantly increased with time over the 96-h incubation period, with EROD activity increasing from 63.6 +/- 14.2 at 24 h to 905 +/- 291 pmol/mg/min at 96 h. Under identical incubation conditions, but in the absence of TCDD, the EROD activity for the control liver slices ranged from 14. 3 +/- 4.3 to 44.9 +/- 11.9 pmol/min/mg. Conversely, the level of CYP1A2 protein and its respective activity (acetanilide hydroxylation) transiently decreased from 24 to 96 h with no significant differences observed between the control (0 nM TCDD) and treatment group (0.01 nM TCDD). The concentration-effect relationship at 96 h was characterized by incubating rat liver slices for the initial 24 h in medium containing TCDD at concentrations ranging from 0.1 pM to 10 nM. Induction of CYP1A1 protein and EROD activity was observed for all treatment groups with the 10 nM TCDD treatment group displaying greater than 100-fold induction compared to control (0 nM TCDD). Immunohistochemical localization of CYP1A1 protein within liver slices supported the time- and concentration-dependent induction of EROD activity by TCDD. The induction of CYP1A1 was initially observed to be centrilobular, with increased expression due to both elevated CYP1A1 within cells and the recruitment of additional cells expressing CYP1A1 throughout the entire liver slice. Additionally, the immunohistochemical analysis of the liver slices demonstrated the conservation of tissue architecture following up to 96 h of incubation in dynamic organ culture and provided further evidence for maintenance of tissue viability. In comparison to CYP1A1, the induction of CYP1A2 at 96 h was a less sensitive response, with significant induction of CYP1A2 protein and its respective activity occurring at a medium concentration of 0.1 nM TCDD (686 pg/g liver). In general, increasing the incubation period from 24 to 96 h markedly increased TCDD-induced expression of CYP1A1 and minimally enhanced CYP1A2 expression. Moreover, extending the incubation period to 96 h resulted in in vitro induction profiles for CYP1A1 and CYP1A2 that were qualitatively and quantitatively similar to that previously observed following in vivo exposure to TCDD (Drahushuk et al., Toxicol. Appl. Pharmacol. 140, 393-403, 1996).     

Validation of Partin tables for predicting pathological stage of clinically localized prostate cancer

PURPOSE: The accurate prediction of pathological stage of prostate cancer using preoperative factors is a critical aspect of treatment. In 1997 Partin et al published tables predicting pathological stage using clinical stage, Gleason score and prostate specific antigen (PSA). We tested the validity of the Partin tables. MATERIALS AND METHODS: From 1990 to 1996 inclusively 5,780 patients underwent bilateral pelvic lymphadenectomy and radical prostatectomy for prostate cancer at the Mayo Clinic. However, only 2,475 of these patients met all inclusion criteria of no preoperative treatment, known biopsy Gleason score, available preoperative PSA done either before biopsy or more than 28 days after biopsy and clinical stage T1, T2 or T3a. Among the 2,475 patients 15 had positive lymph nodes and planned prostatectomy was abandoned. The receiver operating characteristics (ROC) curve area, observed and predicted Partin rates of each pathological stage, and positive and negative predictive values were used to compare the Mayo study to the Partin tables. RESULTS: The distribution of pathological stage was organ confined in 67% of Mayo cases versus 48% in the Partin study, extracapsular without seminal vesicle or node involvement in 18% versus 40%, seminal vesicle involvement without nodes in 9% versus 7% and were positive nodes in 6% versus 5%. Using the predicted probabilities of Partin et al the ROC curve area for predicted node positive disease was 0.84 for Mayo cases compared to an estimated 0. 82 in the Partin series. The ROC curve area for predicting organ confined cancer was 0.76 for the Mayo Clinic compared to an estimated 0.73 for the Partin series. The observed rates of node positive disease were similar to those predicted (Partin) based on clinical stage, PSA and Gleason score. For organ confined disease Mayo rates were consistently higher than those predicted from the Partin series using a cut point of 0.50 or greater. Positive and negative predictive values were 0.83 and 0.49 versus 0.63 and 0.70 for the Mayo Clinic and Partin series. CONCLUSIONS: Our study provides strong evidence that sensitivity and specificity of the Partin tables for external clinical sites are similar to what was reported.     

Fluorescent in vivo tracking of hematopoietic cells. Part I. Technical considerations

We report a new technology for in vivo tracking of hematopoietic cells, using fluorescent lipophilic probes. Because the probe is irreversibly bound in the lipids of the cell membrane; substantial numbers of dye molecules can be incorporated per cell and thus substantial signal to noise can be achieved. Although this technology can be used for all hematopoietic cells, these first findings are reported on red blood cells (RBCs) owing to the importance of the membrane to RBC function and integrity. We demonstrated that labeling 10% of the RBCs of a rabbit and reinjecting them into the animal makes possible the tracking of these cells at various times after injection. Furthermore, the labeling appears not to affect in vivo cell lifetime or cellular volume changes in response to hypotonic shock. The single cell fluorescence intensity of the labeled RBCs remains relatively constant for 60 days, and an immune response appears not to be generated against labeled cells. That labeled RBCs have lifetime kinetics in vivo, as shown in other studies, indicates that the membranes are functioning normally and are unaltered by the labeling technology. The technology we present is also applicable to white blood cells, bone marrow, and platelets.     

Aberrant expression of G1-phase cell cycle regulators in flat and exophytic adenomas of the human colon

BACKGROUND & AIMS: The G1/S-phase controlling mechanism known as the RB pathway is commonly deregulated in human malignancies. Here, the abundance and localization of key components of the retinoblastoma (RB) pathway were determined in exophytic and flat colorectal adenomas. METHODS: Samples of normal colonic mucosa (n = 41) and flat (n = 45) and exophytic (n = 26) adenomas were examined immunohistochemically using antibodies to cyclins D1, D2, D3, cyclin-dependent kinase (CDK) 4, retinoblastoma protein (pRB), and the CDK inhibitors p16INK4a, p18INK4c, and p19INK4d. RESULTS: In normal colonic epithelium, cyclin D2 was undetectable; expression of cyclin D1, CDK4, and pRB correlated with proliferation; and p16, p18, p19, and cyclin D3 were most abundant in quiescent, differentiated cells. Adenomas showed elevated expression of cyclin D1 and pRB, frequent induction of cyclin D2, and absence of p16. No obvious abnormalities were found for p18, p19, or cyclin D3. Overexpressed cyclin D2 was more common among exophytic and pRB among flat adenomas, respectively. Elevated cyclin D1, D2, and CDK4 correlated with enhanced dysplasia. CONCLUSIONS: Aberrant expression of cyclins D1, D2, CDK4, p16, and pRB occur in significant subsets of exophytic and flat adenomas, particularly among cases with high-grade dysplasia. Such defects of the RB pathway may perturb cell-cycle control and thereby contribute an early step in colorectal tumorigenesis.     

Impact of trainee involvement with robotic-assisted radical prostatectomy

Robotic-assisted surgery has been rapidly adopted within urology practice. As a result, academic centers are challenged with the burden of how to effectively train residents and fellows to perform robotic-assisted surgery without compromising outcomes. We evaluated the perioperative outcomes of trainee involvement with robotic-assisted radical prostatectomy (RARP) within our healthcare organization. We retrospectively reviewed RARP cases performed at our institution between September 2008 and December 2010 using a single da Vinci robotic platform. Trainees consisted of urology residents and fellows who operated with staff surgeons on select operating days, whereas two staff surgeon teams performed RARP on alternate days. We compared clinicopathologic variables including operating time, estimated blood loss, surgical margin rates, and complication rates between the trainee and staff-only surgeon groups. Overall, 1,019 RARP surgeries were performed within the study period and trainees participated in 162 cases (16 %). Clinical characteristics were similar between men undergoing surgery with a trainee and those without. Positive surgical margin rates were lower for patients with pT2 disease for cases with trainee involvement (11 vs. 19 %, p = 0.02), although overall margin rates and margin rates for patients with pT3 disease were similar between the groups (p = 0.34). Surgical cases involving trainees were longer (241 vs. 200 min, p < 0.001) and resulted in higher estimated blood loss (190 vs. 120 mL, p < 0.001) than the two staff surgeon cases. However, transfusion rates as well as intraoperative and postoperative complication rates did not differ significantly between groups. In conclusion, surgical margin rates were lower in teaching cases for patients with pT2 disease. Importantly, trainee involvement in RARP is safe, with similar perioperative outcomes to staff-only surgical cases. This information may be useful for training and surgical planning.     

Extracting data from electronic medical records: validation of a natural language processing program to assess prostate biopsy results

Objective

The extraction of specific data from electronic medical records (EMR) remains tedious and is often performed manually. Natural language processing (NLP) programs have been developed to identify and extract information within clinical narrative text. We performed a study to assess the validity of an NLP program to accurately identify patients with prostate cancer and to retrieve pertinent pathologic information from their EMR.

Materials and methods

A retrospective review was performed of a prospectively collected database including patients from the Southern California Kaiser Permanente Medical Region that underwent prostate biopsies during a 2-week period. A NLP program was used to identify patients with prostate biopsies that were positive for prostatic adenocarcinoma from all pathology reports within this period. The application then processed 100 consecutive patients with prostate adenocarcinoma to extract 10 variables from their pathology reports. The extraction and retrieval of information by NLP was then compared to a blinded manual review.

Results

A consecutive series of 18,453 pathology reports were evaluated. NLP correctly detected 117 out of 118 patients (99.1 %) with prostatic adenocarcinoma after TRUS-guided prostate biopsy. NLP had a positive predictive value of 99.1 % with a 99.1 % sensitivity and a 99.9 % specificity to correctly identify patients with prostatic adenocarcinoma after biopsy. The overall ability of the NLP application to accurately extract variables from the pathology reports was 97.6 %.

Conclusions

Natural language processing is a reliable and accurate method to identify select patients and to extract relevant data from an existing EMR in order to establish a prospective clinical database.