The role of growth factor administration and T-cell recovery after peripheral blood progenitor cell transplantation in the treatment of solid tumors: results from a randomized comparison of G–CSF and GM–CSF

BACKGROUND: Peripheral blood progenitor cell (PBPC) transplantation (PBPCT) combined with post-PBPCT administration of myelopoietic growth factors is a valid therapeutic intervention to rapidly restore hematopoiesis after the delivery of intensive, myeloablative cancer chemotherapy. On the other hand, the best growth factor regimen to potentiate PBPC-mediated immunohematopoietic recovery has yet to be determined. STUDY DESIGN AND METHODS: In a randomized evaluation, the effects produced by post-PBPCT G-CSF and GM-CSF on myeloid/lymphoid recovery and transplant outcome in women with chemosensitive cancer were compared. Thirty-seven ovarian cancer patients and 34 breast cancer patients ranging in age from 24 to 60 years were treated with carboplatin, etoposide, and melphalan (CEM) high-dose chemotherapy and then randomly assigned to receive G-CSF (5 microg/kg subcutaneously) or GM-CSF (5 microg/kg subcutaneously) until Day 13 after PBPCT. Patients were compared in regard to hematopoietic recovery, posttransplant clinical management, and immune recovery. Finally, clinical outcome was estimated as time to progression and overall survival. RESULTS: Hematopoietic recovery and posttransplant clinical management were comparable in both the G-CSF and GM-CSF series. Conversely, significantly higher T-cell counts were observed in G-CSF-treated patients during the early and late posttransplant follow-up. Patients who received G-CSF showed a significantly longer median time to progression. A parallel analysis revealed that patients in whom a higher CD3+ count was recovered had a significantly longer overall survival and time to progression. CONCLUSION: The enhancement of post-PBPCT T-cell recovery observed in G-CSF-treated patients encourages the use of G-CSF to ameliorate immune recovery, which seems to play a role in post-PBPCT control of disease in cancer patients. GM-CSF might be administered to prolong immunosuppression after autologous PBPCT for autoimmune diseases or allogeneic PBPCT.     

Comparative evaluation of surgical laparoscopic techniques costs in public and private health systems

Due to the fact that in Romania there are two health systems, public and private, some questions have been raised regarding the efficiency of a certain system, taking into account the quality but also the costs of provided services. Material and method: The study compares the costs of laparoscopic surgical techniques, analysing the causes of the differences that were found, if that were some advantages offered by one of the system to another and if there is a possibility of complementarity perspective between those two medical assistance organisation methods.     

Increased Acid Sphingomyelinase Activity in Peripheral Blood Cells of Acutely Intoxicated Patients With Alcohol Dependence

Background:  Acid sphingomyelinase (ASM; EC 3.1.4.12) hydrolyses membrane sphingomyelin into the bioactive lipid ceramide and is thus involved in different cellular processes such as differentiation, immunity, or cell death. Activation of ASM has been reported in particular in conjunction with the cellular stress response to several external stimuli, and increased ASM activity was observed in a variety of human diseases. Ethanol-induced activation of ASM has been observed in different cell culture systems, thus raising the question about the effect of alcohol intoxication in human subjects on ASM activity in vivo.
Methods:  We determined ASM activity in peripheral blood mononucleated cells of 27 patients suffering from alcohol dependence. Patients were classified according to their blood alcohol concentration at admission, and ASM activity was determined repeatedly from all patients during alcohol withdrawal.
Results:  Acutely intoxicated patients displayed significantly higher ASM activity than patients in early abstinence (Mann–Whitney U test: Z  = − 2.6, p  = 0.009). ASM activity declined in acutely intoxicated patients to normal values with the transition from the intoxicated state to early abstinence (Wilcoxon test: Z  = −2.7, p  = 0.007). At the end of withdrawal, ASM activity was significantly increased again compared to the early phase of abstinence in both patient groups (Wilcoxon test: Z  = −2.691, p  = 0.007 and Z  = −2.275, p  = 0.023, respectively).
Conclusions:  Alcohol-induced activation of ASM occurs in human subjects and might be responsible for deleterious effects of ethanol intoxication. Chronic alcohol abuse may induce deregulation of sphingomyelin metabolism in general, and this impairment may cause side effects during withdrawal from alcohol.     

Haemocompatibility improvement of metallic surfaces by covalent immobilization of heparin-liposomes

Stainless steel surfaces were processed by means of plasma enhanced chemical vapor deposition (PE-CVD) fed with acrylic acid vapors in order to functionalize them with carboxyl groups, which were subsequently activated for covalent immobilization of heparin-loaded (HEP) NH(2) group-functionalized (Fun) nanoliposomes (NLs). Empty Fun or HEP non-functionalized (control) NLs were used as controls. NLs were characterized for mean diameter, surface charge and heparin encapsulation/release. Different lipid compositions were used for NL construction; PC/Chol (2:1mol/mol) or PC/Chol (4:1mol/mol) (fluid type vesicles) [which allow gradual release of heparin] and DSPC/Chol (2:1mol/mol) (rigid type vesicles). Surface haemocompatibility was tested by measuring blood clotting time. Platelet adhesion on surfaces was evaluated morphologically by SEM and CLSM. The haemocompatibility of plasma-processed surfaces was improved (compared to untreated surfaces); Fun-HEP NL-coated surfaces demonstrated highest coagulation times. For short surface/blood incubation periods, surfaces coated with Fun-HEP NLs consisting of PC/Chol (2:1) had higher coagulation times (compared to DSPC/Chol NLs) due to faster release of heparin. Heparin release rate from the various NL types and surface platelet adhesion results were in agreement with the corresponding blood coagulation times. Concluding, covalent immobilization of drug entrapping NLs on plasma processed surfaces is a potential method for preparation of controlled-rate drug-eluting metallic stents or devices.     

Identification and Management of Women at High Risk for Hereditary Breast/Ovarian Cancer Syndrome

Abstract:  Despite advances in identifying genetic markers of high risk patients and the availability of genetic testing, it remains challenging to efficiently identify women who are at hereditary risk and to manage their care appropriately. HughesRiskApps, an open-source family history collection, risk assessment, and Clinical Decision Support (CDS) software package, was developed to address the shortcomings in our ability to identify and treat the high risk population. This system is designed for use in primary care clinics, breast centers, and cancer risk clinics to collect family history and risk information and provide the necessary CDS to increase quality of care and efficiency. This paper reports on the first implementation of HughesRiskApps in the community hospital setting. HughesRiskApps was implemented at the Newton-Wellesley Hospital. Between April 1, 2007 and March 31, 2008, 32,966 analyses were performed on 25,763 individuals. Within this population, 915 (3.6%) individuals were found to be eligible for risk assessment and possible genetic testing based on the 10% risk of mutation threshold. During the first year of implementation, physicians and patients have fully accepted the system, and 3.6% of patients assessed have been referred to risk assessment and consideration of genetic testing. These early results indicate that the number of patients identified for risk assessment has increased dramatically and that the care of these patients is more efficient and likely more effective.     

Obesity does not increase the risk of lymph node metastases in patients with clinically localized prostate cancer undergoing radical prostatectomy and extended pelvic lymph node dissection

Objectives: Several studies have shown that obesity is associated with more aggressive prostate cancer (PCa) variants. We hypothesized that obesity, quantified as body mass index (BMI), is associated with a higher risk of lymph node invasion (LNI) in patients undergoing extended pelvic lymph node dissection (ePLND). Methods: Clinical and pathological data were available for 994 consecutive men with PCa treated with radical prostatectomy (RP) and ePLND at a single European tertiary academic centre. Univariable and multivariable logistic regression analyses addressed the rate of LNI. Covariates consisted of pre‐treatment prostate specific antigen (PSA), biopsy Gleason sum, clinical stage history of diabetes mellitus as well as BMI coded as either continuous or categorized (<25, 25.0–29.9, 30 kg/m² or more) variable. Predictive accuracy was assessed with area under curve estimates. Results: Overall LNI was diagnosed in 105 patients (10.6%). Mean number of removed lymph nodes was 18.3 (range 7–60). Of all 994 patients, 372 (37.4%) were normal weight, 518 (52.1%) overweight, and 104 (10.5%) were clinically obese. Prevalence of LNI did not significantly differ across different BMI categories (<25, 25.0–29.9 and 30 kg/m² or more; 9.9, 10.6 and 12.5%, respectively; P = 0.75). In logistic regression models, neither continuously coded nor categorized BMI was a significant predictor of LNI at univariable or multivariable analyses (all P‐values ≥0.1). Moreover, inclusion of BMI with PSA, clinical stage, biopsy Gleason sum and presence of DM did not increase the ability of these variables to predict LNI (82.2% without BMI vs 82.5% and 82.9% with BMI coded as continuous and categorized variable, respectively; all P ≥ 0.4). Conclusions: In men undergoing RP and ePLND, increased BMI was not associated with increased risk of lymph node metastases. Therefore, routinely considering patient BMI in risk stratification schemes or prognostic LNI models may not be warranted.     

The patterns of spontaneous Ca2+ signals generated by ventral spinal neurons in vitro show time-dependent refinement

Embryonic spinal neurons maintained in organotypic slice culture are known to mimic certain maturation-dependent signalling changes. With such a model we investigated, in embryonic mouse spinal segments, the age-dependent spatio-temporal control of intracellular Ca²⁺ signalling generated by neuronal populations in ventral circuits and its relation with electrical activity. We used Ca²⁺ imaging to monitor areas located within the ventral spinal horn at 1 and 2 weeks of in vitro growth. Primitive patterns of spontaneous neuronal Ca²⁺ transients (detected at 1 week) were typically synchronous. Remarkably, such transients originated from widespread propagating waves that became organized into large-scale rhythmic bursts. These activities were associated with the generation of synaptically mediated inward currents under whole-cell patch-clamp. Such patterns disappeared during longer culture of spinal segments: at 2 weeks in culture, only a subset of ventral neurons displayed spontaneous, asynchronous and repetitive Ca²⁺ oscillations dissociated from background synaptic activity. We observed that the emergence of oscillations was a restricted phenomenon arising together with the transformation of ventral network electrophysiological bursting into asynchronous synaptic discharges. This change was accompanied by the appearance of discrete calbindin immunoreactivity against an unchanged background of calretinin-positive cells. It is attractive to assume that periodic oscillations of Ca²⁺ confer a summative ability to these cells to shape the plasticity of local circuits through different changes (phasic or tonic) in intracellular Ca²⁺.