Contribution of autologous blood transfusion in cardiac surgery in the adult

The use of autologous blood transfusion in cardiac surgery is still controversial. This study was prospectively designed to evaluate the haemodynamic and haematological benefits of this method, with special attention to its impact on reducing bank blood requirements. Between November 1983 and October 1984, 160 patients underwent cardiac surgery with extracorporeal circulation and were randomly assigned to two groups: group I (81 patients) was the control group and group II (79 patients) received autologous transfusion following extracorporeal circulation. Blood was withdrawn immediately after the induction of anaesthesia via a jugular catheter and stored in CPD solution at room temperature. The volume of blood removed was replaced with gelatin solutions; after bypass, blood was returned to the patient. There was no difference in systolic, diastolic or mean blood pressures between the two groups. Right atrial pressure and heart rate were not statistically different in both groups. Myocardial perfusion and myocardial oxygen consumption remained unchanged in group II compared with group I. Complete haematological evaluation was carried out before and during bypass, and thereafter daily for the first twelve days of the postoperative period. There was no significative difference between the two groups in platelet counts, fibrinogen levels, prothrombin and partial thromboplastin times. During extracorporeal circulation, mean haematocrit was 22.9 +/- 0.4% in group II and 25.3 +/- 0.5% in group I (p less than 10(-3)). The mean haematocrit time course was similar in both groups during the postoperative period and returned to preoperative value at discharge.(ABSTRACT TRUNCATED AT 250 WORDS)     

Primary chemotherapy in the treatment of breast cancer]

Between 1980 and 1992, 457 consecutive patients with initial breast cancer entered two successive protocols combining neoadjuvant chemotherapy, hormonotherapy (tamoxifen) and locoregional radiotherapy (teleradiotherapy and boost by iridium) as exclusive locoregional treatment. Cytological diagnosis, hormone receptors, cytological grading were provided by fine needle aspiration. Both protocols included velbe, thiotepa, methotrexate, 5FU and adriamycin with some minor differences regarding the schedule of doses and their number during induction and during the consolidation phase. In both studies, over 50% patients had locally advanced breast cancer (IIb, IIIa or IIIb). Chemotherapy induced tumor regression over 50% in 91% patients of the first protocol (30% complete clinical remission CR) and in 94% patients of the 2nd protocol (40% CR): in this protocol 20 poor responders were given a rescue protocol (2 CR; 9 partial remissions). The 5 year actuarial rate of breast preservation is 94% and the 5 year actuarial rate of local relapses is 15%. The cosmetic results according to Danoff are excellent 20%, good 55%, mean 35%. Disease free survival and overall survival compare favorably to published data: they depend on TNM stages, tumor differentiation and chemotherapy induced early tumor regression.     

Regulation of Ca2+ current in frog ventricular myocytes by the holding potential,c-AMP and frequency

The whole-cell patch-clamp technique was used to study the effects of holding potential and frequency on the Ca2+ current in frog ventricular myocytes. INa was blocked by TTX, and ica was activated with depolarizing clamps from different holding potentials. Variation of the holding potential revealed three new effects on ica: (1) At -40 mV iCa declined with a time constant of 15 min, while at -90 mV, this irreversible decline (run down) in iCa did not occur. (2) The decline of iCa at -40 mV was biphasic: run down was preceeded by a slow inactivation with a time constant of 40 s, which was reversible upon returning the holding potential to -90 mV. (3) Increasing the frequency of the clamp pulses from 0.1 to 1 Hz led to a rapid decline of iCa when the holding potential was positive to -60 mV, but at -90 mV had either no effect or increased iCa by 35%, if c-AMP was included in the dialyzing solution. On the other hand, c-AMP did not alter the time course of the run down and the slow inactivation. Replacement of extracellular Ca2+ by Ba2+ markedly slowed iCa kinetics, but did not change the very slow inactivation or the frequency-induced enhancement of iCa. Injection of c-AMP led to a transient increase of iCa. The phosphodiesterase inhibitor theophylline enhanced the amplitude of the transient and slowed its decay. This effect was mimicked by increased frequency. It is concluded that frequency-induced enhancement of iCa is highly dependent on the holding potential, independent of Ca2+, and may involve elevation of the intracellular level of c-AMP via inhibition of phosphodiesterase activity. The new type of very slow inactivation is probably under direct voltage control and independent of Ca2+ and c-AMP.     

Phase I study of Datelliptium chloride,hydrochloride given by 24-h continuous intravenous infusion

Summary Datelliptium chloride, hydrochloride (SR 95 156B, NSC 626718X, DHE) was studied in a phase I trial of escalating doses given on a single 24-h continuous intravenous infusion schedule. Doses were escalated from 40 to 500 mg/m² in 19 patients who received a total of 24 courses. Courses were repeated after a minimal interval of 3 weeks. Local venous toxicity occurred at low doses (100 mg/m²) and was circumvented by the use of a central venous access for higher doses. Other clinical adverse events occurred (330 mg/m²), including moderate nausea and vomiting, mild diarrhea, dry mouth, neuropsychiatric manifestations, and fatigue. All of these side effects were reversible and none was dose-limiting. The dose-limiting toxicity was related to hepatic laboratory-test abnormalities in the form of reversible elevations of levels of serum bilirubin and liver enzymes at doses of 330 mg/m². The maximum tolerated dose for this schedule is 500 mg/m². Hematologic toxicity was minimal and non-dose-limiting. Neither drug-related deaths nor objective complete or partial responses were observed. However, a minor response and a long-term disease stabilization were obtained.     

In vitro effects of desflurane, sevoflurane, isoflurane, and halothane in isolated human right atria

BACKGROUND: Direct myocardial effects of volatile anesthetics have been studied in various animal species in vitro. This study evaluated the effects of equianesthetic concentrations of desflurane, sevoflurane, isoflurane, and halothane on contractile parameters of isolated human atria in vitro. METHODS: Human right atrial trabeculae, obtained from patients undergoing coronary bypass surgery, were studied in an oxygenated (95% O2-5% CO2) Tyrode's modified solution ([Ca2+]o = 2.0 mM, 30 degrees C, stimulation frequency 0.5 Hz). The effects of equianesthetic concentrations (0.5, 1, 1.5, 2, and 2.5 minimum alveolar concentration [MAC]) of desflurane, sevoflurane, isoflurane, and halothane on inotropic and lusitropic parameters of isometric twitches were measured. RESULTS: Isoflurane, sevoflurane, and desflurane induced a moderate concentration-dependent decrease in active isometric force, which was significantly lower than that induced by halothane. In the presence of adrenoceptor blockade, the desflurane-induced decrease in peak of the positive force derivative and time to peak force became comparable to those induced by isoflurane. Halothane induced a concentration-dependent decrease in time to half-relaxation and a contraction-relaxation coupling parameter significantly greater than those induced by isoflurane, sevoflurane and desflurane. CONCLUSIONS: In isolated human atrial myocardium, desflurane, sevoflurane, and isoflurane induced a moderate concentration-dependent negative inotropic effect. The effect of desflurane on time to peak force and peak of the positive force derivative could be related to intramyocardial catecholamine release. At clinically relevant concentrations, desflurane, sevoflurane, and isoflurane did not modify isometric relaxation.     

Impact of EGFR expression on colorectal cancer patient prognosis and survival.

BACKGROUND: Epidermal growth factor receptor (EGFR) is overexpressed in many types of cancers, especially colorectal cancer (CRC), and seems to reflect more aggressive histological and clinical behaviors. The aim of this study was to evaluate EGFR immunohistochemical reactivity in CRC biopsies, and to analyze its relationship with various histological and clinical characteristics and survival. PATIENTS AND METHODS: A composite EGFR score, obtained by multiplying the grade (% positive cells) by the intensity of labeling (0-9) was used to define patients with low or high EGFR expression whose clinicopathological features were then compared. Univariate tests and multivariate Cox proportional hazards model were applied for data analysis. RESULTS: Tissue sections from 150 CRC patients with a median follow-up of 40 months were examined. Median patient age at diagnosis was 70 years (range 38-89 years). EGFR reactivity was positive for 143 patients (97%) and high for 118 (80%). According to multivariate analysis, EGFR overexpression was significantly associated with tumor stage, with a higher percentage of EGFR overexpression in T3 than T4 (P=0.003) and not with overall survival. CONCLUSIONS: EGFR was overexpressed in this CRC patient population and was significantly associated with TNM (tumor-node-metastasis) stage T3. In the context of a new therapeutic strategy using EGFR-targeted therapies, although EGFR remains a controversial prognostic factor, this expression-stage association may play a crucial role in a decision to initiate an adjuvant treatment.     

Appraisal of synthetic cationic Gemini surfactants as highly efficient inhibitors for carbon steel in the acidization of oil and gas wells: an experimental and computational approach

New cationic Gemini surfactant (CGS) molecules were synthesized and investigated as anticorrosive materials for carbon steel (CS) in 1 M HCl solution by chemical, electrochemical and theoretical studies such as DFT and MDS approaches. The anticorrosion efficacy increased with the increase in the CGS concentration. It reached 95.66% at 5 × 10⁻³ M of the CGS molecule using PDP measurements. PDP studies confirm that the CGS molecule acts as a mixed inhibitor. The EIS outcomes were explained by an equivalent circuit in which a constant phase element (CPE) rather than a double-layer capacitance (C_dl) was exploited to donate a more precise fit of the experimental outcomes. The CGS molecule follows the Langmuir isotherm as it is chemically adsorbed onto the surface of CS. To explore the kinetic and adsorption mechanisms, the thermodynamic characteristics of the activation and adsorption processes were assessed under the impact of temperature. Frontier molecular orbitals (FMOs) were achieved by the density functional theory (DFT) method. The study of interatomic interactions at the [CS (Fe(110))]/CGS level was discussed using molecular dynamics (MD) simulation.

New cationic Gemini surfactant (CGS) molecules were synthesized and investigated as anticorrosive materials for carbon steel (CS) in 1 M HCl solution by chemical, electrochemical and theoretical studies such as DFT and MDS approaches.     

Idiopathic Granulomatous Mastitis: A Heterogeneous Disease with Variable Clinical Presentation

Introduction Idiopathic granulomatous mastitis (IGM) is a rare benign inflammatory breast disease that presents with variable local manifestations. We describe here the different management protocols based on the clinical presentation of these patients. Methods A retrospective review of 20 histopathologic confirmed cases of IGM seen over a period of 10 years was performed. Results The median age was 34 years (age range: 21–45 years). All were married, parous with history of breast feeding. Ill-defined mass mimicking carcinoma was the commonest presentation (70%); however, with the presence of signs of inflammation like pain (55%), redness (40%), and peau d’orange (40%), an inflammatory process appeared more likely. Axillary lymph node enlargement was infrequently seen (40%). Radiologic findings (mammography and ultrasound) were nonspecific. Histopathology showed the characteristic lobular distribution of granulomatous inflammation in all cases. Surgically, 7 patients had abscess drainage with open biopsy, and 7 patients had lumpectomy. Six patients with diffuse breast involvement were diagnosed by core needle biopsy only. Microbial cultures showed no growth. Antibiotics were given empirically when signs of inflammation where present. Two patients needed further abscess drainage followed by persistent sinus excision 3–6 weeks later. The median follow-up was 24 months (range: 15–42 months). Seventeen patients (85%) were recurrence-free, and 3 patients (15%) were lost to follow-up. Conclusions Management of IGM cases needs to be tailored according to the clinical presentation. Precise radiologic and pathologic data interpretation by a multidisciplinary breast team will facilitate diagnosis and minimize unnecessary intervention.     

Toll-like receptors and their ligands control mesenchymal stem cell functions.

Mesenchymal stem cells (MSCs) are widespread in adult organisms and may be involved in tissue maintenance and repair as well as in the regulation of hematopoiesis and immunologic responses. Thus, it is important to discover the factors controlling MSC renewal and differentiation. Here we report that adult MSCs express functional Toll-like receptors (TLRs), confirmed by the responses of MSCs to TLR ligands. Pam3Cys, a prototypic TLR-2 ligand, augmented interleukin-6 secretion by MSC, induced nuclear factor kappa B (NF-kappaB) translocation, reduced MSC basal motility, and increased MSC proliferation. The hallmark of MSC function is the capacity to differentiate into several mesodermal lineages. We show herein that Pam3Cys inhibited MSC differentiation into osteogenic, adipogenic, and chondrogenic cells while sparing their immunosuppressive effect. Our study therefore shows that a TLR ligand can antagonize MSC differentiation triggered by exogenous mediators and consequently maintains the cells in an undifferentiated and proliferating state in vitro. Moreover, MSCs derived from myeloid factor 88 (MyD88)-deficient mice lacked the capacity to differentiate effectively into osteogenic and chondrogenic cells. It appears that TLRs and their ligands can serve as regulators of MSC proliferation and differentiation and might affect the maintenance of MSC multipotency.