Detection of C-erb B2 gene amplification in bilharzial associated bladder cancer using fluorescence in situ hybridization

BACKGROUND: Gene amplifications are common events in different tumor types and may confer diagnostic, prognostic, or therapeutic information for patient management. Fluorescence in situ hybridization (FISH) represents a standard methodologic approach for testing for this genetic alteration, as it is rapid, reproducible and extremely reliable in detecting presence of C-erb-B2 gene amplification for clinical utility. PATIENTS AND METHODS: In this study, FISH is used in a series of archival human bilharzial bladder cancer specimens to evaluate for the presence of cerbB-2 gene alterations in the most common malignant tumor in bilharzial endemic areas, e.g., Egypt and some other countries. The study included 40 cases, 30 males and 10 females. Their ages ranged between 30 years and 76 years (median: 51 years). Twenty-one cases had squamous cell carcinoma, 16 had transitional cell carcinoma, two had adenocarcinoma, and one case had undifferentiated carcinoma. RESULTS: Thirteen out of 40 tumor samples (32.5%) show evidence of true C-erb-B2 gene amplification. Of the remaining samples, 24 (60%) show no gene amplification and three (7.5%) fall into the borderline category with a ratio between one and two C-erb-B2 genes/cell relative to chromosome 17 centromeres. No evidence of chromosome 17 polysomy was found in any cases scored as single copy with the C-erb-B2 probe. CONCLUSION: No significant association was found between gene amplification and any of the tested clinicopathologic parameters or tumor recurrence except for tumor grade where higher tumor grades tended to be associated with more C-erb-B2 gene amplification (P = 0.01) thus reflecting more tumor aggressiveness. So, the amplification of C-erb-B2 in bilharzial associated bladder cancer is probably not independently related to clinical outcome of patients.     

Outcome of low-dose ganciclovir for cytomegalovirus disease prophylaxis in renal-transplant recipients

To assess the outcome of low-dose-ganciclovir prophylaxis (500 mg twice a day for 3 months) in renal-transplant recipients, a retrospective analysis of 185 patients transplanted between 1998 and 2001 was performed. There were 29 (15.6%) patients who belonged to the highest risk group, donor cytomegalovirus (CMV) positive, recipient negative (D + R-), and 37 (20%) patients in the lowest risk group, D-R-. Induction immunosuppression consisted of polyclonal antibody or OKT3 (n = 62, 33.5%), interleukin-2 receptor antibody (n = 61, 33%), and no induction (n = 62, 33.5%). CMV disease occurred in 13 (7%) patients. Highest incidence was in D + R- group (17.2%), with no cases in D-R- group (P = 0.03). Tissue-invasive CMV occurred in 4 of these 13 patients. In patients developing CMV disease, there was no evidence of ganciclovir resistance and no mortality over a mean follow-up of 42 months. Low-dose ganciclovir was found to be as effective in decreasing the incidence of clinical CMV disease as high-dose ganciclovir (1 gm three times a day for 3-6 months) in previous studies.     

Treatment of established recurrent hepatitis C in liver-transplant recipients with pegylated interferon-alfa-2b and ribavirin therapy

INTRODUCTION: The management issues of transplant patients with hepatitis C virus (HCV) are complex, and interferon therapy is often ineffective. We present data from a retrospective review in liver-transplant recipients suffering from HCV recurrence that were treated with pegylated alpha-2b interferon and ribavirin. METHODS: A retrospective review of transplant recipients that received combination pegylated alpha-2b interferon (1.5 mcg/kg/wk) and ribavirin (400-600 mg/day) therapy intended for at least 48 weeks. Complications were recorded and included neutropenia (<750 cells), anemia (hemoglobin <8 g) with and without treatment consisting of blood transfusions, erythropoietin, or dose reduction of ribavirin, and depression. The diagnosis of HCV recurrence was determined by an increase in liver chemistries, histopathologic findings with inflammation along with viral recurrence using the COBAS AMPLICOR HCV test. RESULTS: Fifty-seven liver-transplant recipients were included, 29 naive (group 1) to therapy and 28 nonresponders (group 2) to at least 6 months of interferon and ribavirin therapy. Eight (27.6%) patients in group 1 and six (21%) patients in group 2 were HCV nondetectable at the end of 48 weeks of therapy. Ribavirin therapy was decreased in 13 of 29 (45%) for group 1 and 11 of 28 (39%) in group 2. Therapeutic interventions were 4 of 57 (7%) blood transfusions, 23 of 57 (40%) erythropoietin, and 17 of 57 (30%) filgrastim. CONCLUSION: Combination pegylated interferon with ribavirin appears to effective therapy in HCV recurrence and in HCV nonresponsive to interferon and ribavirin. This data reveals the difficulty and caution that must be taken when treating HCV-R liver-transplant recipients with combination pegylated alpha-2b interferon and ribavirin therapy.     

The carotid-oculomotor window in exposure of upper basilar artery aneurysms: a cadaveric morphometric study

OBJECTIVE: The carotid-oculomotor window remains the traditional deep window in the exposure of aneurysms of the upper basilar artery. Although several techniques have been described to expand this window, few morphometric studies document either the degree of its expansion or its contribution to the exposure of the basilar artery. We review the microsurgical anatomy of the carotid-oculomotor window, describe expansion techniques, and analyze morphometrically the contribution of each step (i.e., extradural anterior clinoidectomy, mobilization of the internal carotid artery [ICA], and posterior clinoidectomy) to the expansion of the window and/or exposure of the artery. METHODS: Ten formalin-fixed, alcohol-preserved, cadaver heads injected with pigmented silicone were prepared for bilateral dissection. The vertebrobasilar system was injected with pigmented silicone mixed with barium (1:1), rendering it radiopaque. After completing a frontotemporal-orbitozygomatic craniotomy, we performed dissection in two stages: Stage I consisted of a conventional transsylvian exposure of the upper basilar artery through the carotid-oculomotor window; and Stage II added anterior clinoidectomy, ICA mobilization, and posterior clinoidectomy. A clip was applied to the lowest accessible point of the basilar trunk at each stage. Measurements obtained during each stage included: 1). the transverse carotid-oculomotor distance, that is, anteriorly between the oculomotor foramen and ICA, and posteriorly between the oculomotor nerve and ICA; and 2). the exposed length of the basilar artery, as seen under the microscope and on angiograms. RESULTS: Measurements were obtained before and after the addition of anterior clinoidectomy, mobilization of the ICA, and posterior clinoidectomy. Increases in expansion of the window and exposure of the upper basilar artery were documented as percentages of the control values. The anterior carotid-oculomotor distance averaged 7.1 mm (range, 5-10 mm) and 10.1 mm (range, 7-15 mm) before and after the additional surgical steps to expand the window, respectively. The posterior carotid-oculomotor distance averaged 12.7 mm (range, 9-18 mm) and 16.1 mm (range, 11-22 mm) before and after the additional surgical steps to expand the window, respectively. The exposed length of the basilar artery from the bifurcation to the clip was 4.2 mm (range, 1-13 mm) before expansion and 7 mm (range, 3-15 mm) after expansion. CONCLUSION: Anterior clinoidectomy and ICA mobilization increased the carotid-oculomotor space 44% anteriorly and 28% posteriorly. Posterior clinoidectomy increased the exposed length of the basilar artery by 69%. Superficial wide field exposure, expansion of the carotid-oculomotor window, and increased exposure of the upper basilar artery facilitate both visualization of the aneurysm for clip application and the use of proximal vascular control as an adjunct to basilar aneurysm surgery.     

Short review on dopamine agonists: insight into clinical and research studies relevant to Parkinson's disease

Parkinson's disease (PD) is a chronic and progressive neurological disorder characterized by selective degeneration of dopaminergic neurons (DAergic) in the substantia nigra pars compacta (SNpc) and subsequent decrease in dopamine (DA) levels in the striatum. Although levodopa replacement therapy is initially effective in symptomatic treatment of parkinsonian patients, its effectiveness often declines and various levodopa-related side effects appear after long-term treatment. The disabling side effects of levodopa therapy include motor fluctuations such as the wearing-off or on-off phenomena, dyskinesias and psychiatric symptoms. Nowadays, DA receptor agonists are often regarded as first choice in de novo and young parkinsonian patients to delay the onset of levodopa therapy. In advanced stages of the disease, they are also used as adjunct therapy together with levodopa to retard the development of motor complications. DA receptor agonists mimic the endogenous neurotransmitter, dopamine, and act by direct stimulation of presynaptic (autoreceptors) and postsynaptic DA receptors. Next to their clinical role in treating parkinsonian patients, laboratory studies reported antioxidative and neuron-rescuing effects of DA receptor agonists either in vivo or in vitro. This may involve reduced DA turnover following autoreceptor stimulation and direct free radical scavenging activity. In this review, we focus on and summarize the recently reported effects of the most commonly used DA agonists either in clinical or in research studies relevant to PD treatment.     

Assessment of regional left ventricular function: accuracy and reproducibility of positioning standard short-axis sections in cardiac MR imaging

The assessment of regional left ventricular (LV) function with cardiac magnetic resonance (MR) cine techniques requires a standardized section positioning. A simple selective short-axis method for selective positioning of three short-axis sections (basal, midcavity, apical) was tested for its accuracy, compared with accepted criteria, in 21 volunteers (mean age, 32 years +/- 11) and in 23 patients with myocardial infarction (mean age, 56 years +/- 12). Reproducibility of section positioning and of regional LV parameters was tested in the volunteers. Among the six accuracy criteria defined for standard sections, the selective short-axis approach had an average accuracy of 90.9% in volunteers and 87.7% in patients, compared with 92.1% and 90.6%, respectively, for a multisection approach covering the whole LV. There was very good reproducibility of the selected intersection gap (r = 0.89, P < .001) and of measured midcavity end-diastolic diameters in vertical (r = 0.83, P < .001) and horizontal (r = 0.85, P < .001) long-axis orientations. The proposed method produces standardized short-axis section positions that meet the recommendations for cardiac imaging. The study was approved by the local ethics committee, and all subjects gave written informed consent.     

Development and validation of a lower-extremity activity scale. Use for patients treated with revision total knee arthroplasty

BACKGROUND: Valid outcome measurement tools are required to reliably demonstrate the effectiveness and clinical outcomes of lower-extremity arthroplasty. Having ascertained a lack of a practical and valid measure of the change in actual daily physical activity that occurs prior to and following lower-limb arthroplasty, we developed and validated a lower-extremity activity scale. METHODS: The eighteen-level self-administered scale was developed with the aid of content experts to ensure face validity. Validity and reliability were assessed with the use of (1) pedometer measurements of seventy subjects over seven days; (2) next-of-kin proxy measurements of the activity levels of ninety patients before they underwent lower-limb arthroplasty; and (3) application, and correlation with the Western Ontario and McMaster Universities Osteoarthritis Index scores, in a prospective seventeen-center clinical study of 297 consecutive patients undergoing revision total knee arthroplasty. In this latter study, demographic and comorbidity data were also collected. Univariate and bivariate correlations were performed, and a multivariate structured equation modeling approach was used to further test responsiveness, reliability, and validity of the lower-extremity activity scale. RESULTS: Pedometer readings correlated with the activity levels derived with the lower-extremity activity scale (r = 0.79). Of note was the finding that age, weight, and body mass index did not correlate well with the average number of steps per day (r = -0.32, -0.32, and -0.25, respectively). A significant correlation was found between the lower-extremity activity scores recorded by the patients and those reported by their next of kin (Pearson correlation, r = 0.715; p = 0.0001) and between the initial lower-extremity activity scores and two-week-retest scores (intraclass correlation = 0.9147; p < 0.0001), demonstrating the validity and reliability of the scale. The lower-extremity activity scale was responsive, accurately reflecting changes in the patient's condition between baseline and the time of follow-up (p < 0.001), and it was reliable, with baseline values correlating with follow-up scores (p < 0.001). The convergent validity of the lower-extremity activity scale was established by correlations with the function scores (r = -0.301, p < 0.001) and pain scores (r = -0.241, p < 0.001) derived with the Western Ontario and McMaster Universities Osteoarthritis Index and with a higher number of comorbidities (r = -0.244, p < 0.001). Multivariate path modeling further demonstrated diminished activity in patients who had more difficulty in functioning and a greater number of comorbidities. CONCLUSIONS: We developed a lower-extremity activity scale and validated that it was an effective instrument for the assessment of patients' actual activity levels. It is easy to apply and interpret, and it is valid and ready for use in the clinical setting. This scale will allow more accurate analysis and prediction of outcomes. Consequently, it will become a useful, practical adjunct to objective clinical decision-making and intervention for patients undergoing arthroplasty.