Prognostic significance of angiogenesis evaluated by CD105 expression compared to CD31 in 905 breast carcinomas: correlation with long-term patient outcome

Our purpose was to determine the respective prognostic significance of CD105 and CD31 immunoexpression in node negative patients with breast carcinoma, since angiogenesis induces blood borne metastases and death in carcinomas. CD105 (endoglin) has been reported as expressed by activated endothelial cells and consequently should better reflect neoangiogenesis in malignant tumors. Comparison of CD31 and CD105 immunocytochemical expression was undertaken in a series of 905 breast carcinomas. Results were compared to patients' long-term (median = 11.3 years) outcome. Univariate (Kaplan-Meier) analysis showed that the number of CD105+ microvessels (cut-off 15 vessels) correlated significantly with poor overall survival (p=0.001). This correlation was less significant in node negative patients (p=0.035). The number of CD31+ microvessels (cut-off 25 vessels) similarly correlated with poor survival (p=0.032) but not in the subgroup of node negative patients. Marked CD105 expression also correlated with a high risk for metastasis in all patients (p=0.0002) and in the subset of node negative patients (p=0.001). Similarly metastasis risk in node negative patients correlated with marked CD31 immunocytochemical expression (p=0.02). Multivariate analysis (Cox model) identified CD105, but not CD31 immunoexpression, as an independent prognostic indicator. Our results suggest that: i) in breast carcinomas, immunoselection of microvessels containing activated CD105 labelled endothelial cells is endowed with a stronger prognostic significance, as compared to CD31 vessels labelling; ii) the CD105 immunoexpression may be considered as a potential tool for selecting node negative patients with a poorer outcome and higher metastasis risk; iii) in these patients specific antiangiogenic therapy targeted by anti-CD105 conjugates can be further developed.     

Apoptosis and proliferation kinetics of T cells in patients having experienced antiretroviral treatment interruptions

Multiple failures of antiretroviral treatments, as a result of multidrug-resistant virus, have led to a proposal for structured therapeutic interruptions (STI). However, a significant decrease in CD4+ T cells may occur. The aim of our study was to determine the kinetics of T cell subpopulation changes, T cell apoptosis and peripheral blood mononuclear cell proliferation after STI. The impact of resistance mutation disappearance on T cell apoptosis was also studied. Ten patients were enrolled prospectively, and blood sampling was performed at weeks 0, 2, 4, 6, 8 and 12. The mean increase in viral load was 1.3 log(10) copies/ml, ranging from 0.1 to 3.2. CD4+ T cell count decreased to a mean of 80 cells/mm(3) from baseline to week 12. In the same period, CD8+ T cells decreased to a mean of 139 cells/mm(3). A significant increase in both T cell apoptosis and proliferation of mononuclear cells was observed. However, proliferation was an early and brief event. The increase in CD4+ T cell apoptosis was obvious in patients exhibiting complete reversion of resistance mutations to antiviral drugs. Our results suggest that during STI, apoptosis is an overwhelming phenomenon compared with proliferation, and may explain the limited immunological impact of this therapeutic option.     

The use of malleus allografts in ossiculoplasty

OBJECTIVE: To assess the functional performance of remodeled malleus allografts in a malleus-footplate assembly in terms of hearing results and mid long-term stability. STUDY DESIGN: A retrospective study of 60 consecutive patients who underwent a malleus allograft ossiculoplasty from 1993 until 2000. In all cases the incus and the stapedial arch were missing as the result of cholesteatoma (49), chronic otitis (5), incus necrosis resulting from stapes prosthesis (5), and congenital ossicular malformations (1). In all cases malleus allografts were remodeled to form a malleus-stapes assembly. RESULTS: The audiometric results, using such an ossiculoplasty, revealed an overall median gain of 18.3 dB at 2 months, 22.3 dB at 6 months, and 25 dB 1 year postoperatively on Fletcher frequencies. An air-bone gap closure within 20 dB was achieved in 81% of all cases 1 year postoperatively. No cases of extrusion have been seen in our series. CONCLUSION: Our findings suggest that malleus allografts are capable of generating good and stable functional results as malleus-stapes assembly.     

Contribution of magnetic resonance spectrometry to the diagnosis of intracranial tumors

Magnetic resonance spectroscopy (MRS) is a method enabling the analysis of the tissue metabolic content. It may offer a more accurate diagnosis of the intracranial tumors than conventional MRI sequences. MRS of normal brain parenchyma displays 4 main metabolites: N-acetyl aspartate (neuronal marker), creatine (cellular density marker), choline (membrane activity marker) and myoinositol (glial marker); pathological processes lead to variations of the level of these metabolites and/or the appearance of abnormal metabolites (lactate), following different patterns according to pathological process involved: glioma, meningioma, metastasis, bacterial or toxoplasmic abscess, radionecrosis. The potential clinical use of this method includes positive, differential and etiological diagnosis of tumors, determination of the level of malignancy of gliomas, screening for tumor recurrence following treatment. Our laboratory has been performing MR spectroscopic explorations of brain tumors for many years. Based on this experience, we show how MRS can be routinely performed in the clinical setting, what are its limitations and potential, and what kind of information can be supplied to the clinician.     

Clinical experience with two physiologic bicarbonate/lactate peritoneal dialysis solutions in automated peritoneal dialysis

Clinical experience with two physiologic bicarbonate/lactate peritoneal dialysis solutions in automated peritoneal dialysis. BACKGROUND: Patients on automated peritoneal dialysis (APD) usually receive larger volumes of dialysis solution and more frequent, shorter exchanges than patients on continuous ambulatory peritoneal dialysis (CAPD), and therefore are likely to derive greater benefit from more physiologic solutions. METHODS: Peritoneal dialysis solutions containing 25 mmol/L bicarbonate and either 10 or 15 mmol/L lactate were compared with standard lactate solutions (35 or 40 mmol/L) in two prospective, open-label studies of patients on APD. Each study included a 2-week baseline period (lactate solution), a 6-week treatment period (bicarbonate/lactate solution), and a 2-week follow-up period (same lactate solution as baseline). Biochemical analyses and assessments of vital signs and safety parameters were conducted at baseline, every 2 weeks during treatment, and at the end of the follow-up period. A product use questionnaire was administered in one study at the end of treatment. RESULTS: A statistically significant rise in plasma bicarbonate (approximately 2 mmol/L) occurred when patients switched from a lactate solution to the bicarbonate/lactate solution with equimolar buffer concentration (P < 0.001 for each solution). Plasma bicarbonate decreased by 1.16 mmol/L after a switch from lactate 40 mmol/L to bicarbonate/lactate 35 mmol/L (P < 0.001). When patients switched to bicarbonate/lactate 35, the majority of individual venous plasma bicarbonate values were in the normal range. A switch from a lower calcium (1.25 mmol/ L) lactate solution to a higher calcium (1.75 mmol/L) lactate/bicarbonate solution resulted in a statistically significant rise in serum calcium (0.06 mmol/L, P < 0.018). The product use questionnaire revealed improvements in symptoms, including reduced pain on infusion. CONCLUSION: Bicarbonate/lactate solutions may be used safely and effectively in patients on APD. The availability of 2 formulations with different buffer and calcium content provides flexibility for the control of acidosis as well as calcium balance.     

Laparoscopic gastric banding: a minimally invasive surgical treatment for morbid obesity: prospective study of 500 consecutive patients

OBJECTIVE: To evaluate early and late morbidity of laparoscopic adjustable gastric banding for morbid obesity and to assess the efficacy of this procedure by analyzing its results. SUMMARY BACKGROUND DATA: Laparoscopic adjustable gastric banding is considered the least invasive surgical option for morbid obesity. It is effective, with an average loss of 50% of excessive weight after 2 years of follow-up. It is potentially reversible and safe; major morbidity is low and there is no mortality. METHODS: Between April 1997 and June 2001, 500 patients underwent laparoscopic surgery for morbid obesity with application of an adjustable gastric band. There were 438 women and 62 men (sex ratio = 0.14) with a mean age of 40.4 years. Preoperative mean body weight was 120.7 kg and mean body mass index (BMI) was 44.3 kg. m. RESULTS: Mean operative time was 105 minutes, 84 minutes during the last 300 operations. Mean hospital stay was 4.5 days. There were no deaths. There were 12 conversions (2.4%), 2 during the last 300 operations. Fifty-two patients (10.4%) had complications requiring an abdominal reoperation. Forty-nine underwent a reoperation for minor complications: slippage (n = 43, incisional hernias (n = 3), and reconnection of the catheter (n = 3). Three patients underwent a reoperation for major complications: gastroesophageal perforation (n = 2) and gastric necrosis (n = 1). Seven patients had pulmonary complications and 36 patients experienced minor problems related to the access port. At 1-, 2-, and 3-year follow-up, mean BMI decreased from 44.3 kg. m to 34.2, 32.8, and 31.9, respectively, and mean excess weight loss reached 42.8%, 52%, and 54.8%. CONCLUSIONS: Laparoscopic adjustable gastric banding is a beneficial operation in terms of excessive weight loss, with an acceptably low complication rate. It can noticeably improve the quality of life in obese patients. Half of the excess body weight can be effortlessly lost within 2 years.     

Therapeutic possibilities for polyomavirus infections in renal transplantation

TO IMPROVE THERAPEUTIC MANAGEMENT: The aim is the early detection of polyomavirus infection, before the onset of tubulo-interstitial nephritic lesions, and to reduce viral replication. AT THE STAGE OF POLYOMAVIRUS INFECTION: Treatment relies on the reduction of immunosuppression. Efficacy is controlled by monitoring the decoy cells in the urine and the detection and quantification of the DNA of polyomaviruses in the plasma and urine. AT THE STAGE OF POLYOMAVIRUS DISEASE: The aim is to reduce the viral replication by further decreasing immunosuppression to stabilize renal function and avoid graft rejection. When signs of rejection and viral infection co-exist, cidofovir could be a therapeutic alternative. However, the use of cidofovir remains in the field of clinical research and requires the further development of therapeutic protocols.     

Magnetization transfer contrast imaging in Niemann pick type C mouse liver

PURPOSE: To investigate livers of mice afflicted with Niemann Pick type C (NP-C) disease using magnetization transfer contrast (MTC) imaging and to test the hypothesis that the MT ratio reproducibly changes during disease progression. BACKGROUND: NP-C is a heritable defect of lipid metabolism that results in the accumulation of unesterified cholesterol and gangliosides in virtually all cells. Symptoms predominate in brain and liver, which have high endogenous rates of lipid turnover. It is fatal to children, usually early in the second decade of life. Previous work has shown that the efficiency of magnetization transfer (MT) can be affected by cholesterol and collagen in tissues. The MT ratio (MTR) was calculated and compared during growth and therapy of diseased and control mice. RESULTS: Significant differences in the MTR were observed between livers of diseased and control mice. These ratios were consistent with collagen deposition associated with fibrosis, and not the accumulation of unesterified cholesterol in this organ. CONCLUSION: These results indicate that MTC imaging may have clinical potential for monitoring progression and therapy in NP-C disease.