A comparative study of immunohistochemistry and electron microscopy used in the diagnosis of epidermolysis bullosa

Electron microscopic examination still is the gold standard for classifying epidermolysis bullosa, although it is relatively expensive, time consuming, and not readily available. Immunoreagents have been developed recently to map antigens in the basement membrane on routinely processed specimens. The current study was performed to examine the diagnostic usefulness of immunohistochemistry, as compared with electron microscopic examination, for analyzing routine formalin-fixed paraffin-embedded sections of epidermolysis bullosa. This study investigated 39 consecutively diagnosed cases of epidermolysis bullosa in which both electron microscopic examination and immunohistochemistry were used. In each case, three monoclonal antibodies were used to stain for laminin 1, collagen IV, and keratin. The immunohistochemical patterns were defined as follows: epidermolysis bullosa simplex (laminin, collagen IV, or both at the dermal floor of the blister and keratin at both the dermal floor and the epidermal roof), junctional epidermolysis bullosa (laminin, collagen IV, or both at the dermal floor of the blister and keratin only at the epidermal roof), and dystrophic epidermolysis bullosa (collagen IV, laminin, or both, and keratin all at the epidermal roof). Altogether, electron microscopic examination subclassified epidermolysis bullosa into its three major forms in 37 of the 39 cases (95%), and immunohistochemistry in 33 of the 39 cases (85%). All of the classifiable cases were concordant. Specifically, immunohistochemistry was diagnostic in 10 of 14 (71%) epidermolysis bullosa simplex cases, 14 of 14 (100%) junctional epidermolysis bullosa cases, and 9 of 11 (82%) dystrophic epidermolysis bullosa cases. The most frequent cause for inconclusive immunohistochemical results was failure in staining of the basement membrane with the antibodies to both laminin and collagen IV. In conclusion, the use of immunohistochemistry on routinely processed specimens may be useful for subclassifying epidermolysis bullosa into its major forms in the majority of the cases, although it still cannot fully replace electron microscopic examination or immunofluorescence mapping in the diagnosis of epidermolysis bullosa.     

Long-term follow-up in managing anaplastic astrocytoma by multimodality approach with surgery followed by postoperative radiotherapy and PCV-chemotherapy: phase II trial

Overall survival and progression-free survival after 5 and 10 years of 31 patients with malignant glioma treated by a combination of surgery, postoperative radiotherapy, and chemotherapy with a PCV regimen (procarbazine, CCNU [lomustine] and vincristine) is described. Parameters were evaluated by age at diagnosis, gender, ethnic origin, pre- and postsurgery Karnofsky Performance Status (KPS) score, limit and amount of surgical resection, histopathologic type, number of chemotherapy courses, time between surgery and radiotherapy, response to combined therapy, and dosage and type of radiotherapy. Progression-free survival was 29% at 24 months and 22% at 60 and 120 months. Overall survival was 47%, 36%, and 36% after 24, 60, and 120 months, respectively. Favorable prognostic factors for survival in univariate analysis were pre- and postoperative KPS (> or =70; p = 0.015; p = 0.0025, respectively), age of patients (<40; p = 0.01), number of chemotherapy cycles (> or =6; p = 0.02), and radiation dose (> or =60 Gy; p = 0.0015). The only significant prognostic factors for overall survival in a stepwise multivariate analysis were irradiation dose (p = 0.0001), number of chemotherapy cycles (p = 0.001), and preoperative KPS (p = 0.05); for progression-free survival it was number of chemotherapy cycles (p = 0.004). Survival was not affected by excision size, radiation method, histopathologic type of tumor, gender, ethnic origin, or time lapsed between surgery and irradiation.     

Comparisons of nomograms and urologists' predictions in prostate cancer

When applying nomograms to a clinical setting it is essential to know how their predictions compare with clinicians'. Comparisons exist outside of the prostate cancer literature. We reviewed these comparisons and conducted 2 experiments comparing predictions of clinicians with prostate cancer nomograms. By using Medline, we searched studies from January 1966 to July 1999 that compared human predictions with nomogram predictions. Next, we conducted 2 experiments: (1) 17 urologists were presented with 10 case vignettes and asked to predict the 5-year recurrence-free probabilities for each patient; (2) case presentations of 63 prostate cancer patients (including full clinical histories with complete diagnostic data and surgical findings) were made to a group of 25 clinicians who were asked to predict organ-confined disease. We found 22 published studies comparing human experts with nomograms, greater than half (13 of 22) showed the nomogram performing above the level of the human expert. Our first experiment showed urologist modification of 165 nomogram predictions led to a decrease in prediction accuracy (c-index decreased from.67 to.55, P <.05). In our second experiment, clinician predictions of organ-confined disease were comparable to the nomogram (area under the receiver operating characteristic curve [AUC] 0.78 and 0.79, respectively). A mixed-model suggests the nomogram did not augment clinician prediction accuracy (doctor excess error 1.4%, P =.75, 95% confidence interval [CI]: -10.9% to 8.2%). Our data suggest that nomograms do not seem to diminish predictive accuracy and they may be of significant benefit in certain clinical decision making settings.     

Using noise signature to optimize spike-sorting and to assess neuronal classification quality

We have developed a simple and expandable procedure for classification and validation of extracellular data based on a probabilistic model of data generation. This approach relies on an empirical characterization of the recording noise. We first use this noise characterization to optimize the clustering of recorded events into putative neurons. As a second step, we use the noise model again to assess the quality of each cluster by comparing the within-cluster variability to that of the noise. This second step can be performed independently of the clustering algorithm used, and it provides the user with quantitative as well as visual tests of the quality of the classification.     

Exercise hemodynamics of aortic prostheses: comparison between stentless bioprostheses and mechanical valves

BACKGROUND: Nonstented bioprostheses have been associated with lower resting gradients than stented bioprostheses or mechanical valves. We compared the hemodynamic performance of nonstented bioprostheses and mechanical valves with normal native aortic valves at rest and exercise. METHODS: Dobutamine echocardiography was used to assess gradients and effective orifice area index at rest and exercise in patients with the Toronto stentless porcine valve (TSPV; n = 13; mean implant size 25.7 mm), Medtronic Freestyle (FR; n = 11; mean implant size 23.9 mm), Sorin Bicarbon (SOR; n = 11; mean implant size 24.5 mm), St. Jude Medical (SJM; n = 10; mean implant size 21.3 mm), and normal native aortic valves (NOR; n = 10). RESULTS: All groups demonstrated a major rise in cardiac output at maximal dobutamine infusion. At rest and exercise, respectively, mean gradients were 5.48 +/- 1.1 mm Hg and 5.83 +/- 0.9 mm Hg for TSPV, 5.68 +/- 1.2 mm Hg and 7.50 +/- 1.7 mm Hg for FR, 10.29 +/- 1.4 mm Hg and 20.78 +/- 2.7 mm Hg for SJM, 5.26 +/- 0.8 mm Hg and 11.1 +/- 1.8 mm Hg for SOR, and 1.54 +/- 0.4 mm Hg and 2.18 +/- 0.7 mm Hg for NOR. In comparison with normal valves, both stentless groups showed no change in mean gradient at exercise, whereas both mechanical groups showed an increase in gradient at exercise (p < 0.04). CONCLUSIONS: Stentless valves behave similarly to normal aortic valves in that there is almost no increase in gradient at exercise. Both mechanical valve groups showed increased gradients at exercise, suggesting that these valves obstruct blood flow. Our data add further evidence that stentless valves are hemodynamically superior to mechanical valves in the aortic position.     

Oropharyngeal cancer pathogenesis: ubiquitin proteolytic, apoptotic and epidermal growth factor related pathways act in concert--first report

The current study was carried out to examine the clinical characteristics and survival-probability rates of 51 patients treated for oral (tongue) cancer and to correlate it with various tumor markers. The clinical data and survival probability rates were correlated with the immunohistological analysis of p27, Skp2, p53, Bcl-2, TUNEL (apoptotic rate) and c-erbB-2 markers. The 5-year survival-probability correlated with staging, grading and base of tongue location. An inverse relation between the expression of p27 and Skp2, p27 and grading, and a direct relation between Skp2 and grading were demonstrated. Concomitantly, significant correlations between low p27, high Skp2 and high TUNEL (apoptotic rate) expressions and between low p27 and high c-erbB-2 (Her2) expressions in the cancer lesions were demonstrated. The accumulated data may be employed in the future for a better understanding of the biology behind oral cancer and for developing better means of detection and treatment.     

Geometrical analysis of Copeland surface replacement shoulder arthroplasty in relation to normal anatomy

This study examines the effect of humeral head surface replacement on the geometry of the arthritic glenohumeral joint and correlates changes to clinical outcome. Thirty-nine patients undergoing resurfacing arthroplasty were prospectively followed up clinically and radiologically for a mean of 38 months (range, 24 to 72 months). Measurements were taken from coronal radiographs by use of a validated technique. There was an estimated mean 6 mm erosion of preoperative lateral offset (coracoid base to greater tuberosity). The prosthesis reduced the humeral head radius by a mean of 3.5%. Humeral offset (greater tuberosity to center of instant rotation) increased by a mean of 5 mm (95% CI, 3.8 to 6.4; P<.01). Mean age-/sex-adjusted Constant scores improved from 26 to 83 points (P<.01). The improved postoperative motion showed a nonlinear relationship with humeral offset. We conclude that surface replacement restores humeral offset and the lever arm of the deltoid and supraspinatus while otherwise mimicking individual anatomy. Function depends on adequate restoration of this lever arm without overstuffing the joint.     

Stress fracture of the clavicle in a patient with no obvious risk factors

A 28-year-old woman presented with right shoulder pain and, after a delay, a diagnosis of clavicular stress fracture was made. The patient gave no history of repetitive abnormal loading of the upper limbs which could have assisted the diagnosis. The authors wish to raise awareness of this rare diagnosis such that it can be considered in the differential for shoulder pain of unclear origin.