Crenobalneotherapy for low back pain: systematic review of clinical trials.

Crenobalneotherapy is a treatment commonly used in Europe and Middle East. It uses mineral water sometimes combined with different hydrotherapy techniques. Most patients treated in spa centers suffer from low back pain. The purpose of this work is to identify clinical trials on crenobalneotherapy for low back pain. Publication research was performed on Medline, Cochrane, and PEDRO databases. Clinical trials were analyzed for internal validity, external validity, quality of statistical analysis, and quality of collection of adverse events. We present the best level of evidence. Bibliographic research identified 21 clinical trials and the coauthors added 5 references. The 26 trials represent 2695 patients. Some have good methodological quality and allow considering crenobalneotherapy as a potential treatment for low back pain, even if the role of mineral water remains uncertain. The methodological quality of therapeutic trials should be improved. These trials should be analyzed in the future guidelines on low back pain.

[Bilateral simultaneous central retinal artery occlusion revealing giant cell arteritis]. / Occlusion bilaterale et simultanee de l'artere centrale de la retine revelatrice d'une maladie de Horton.

AIM: To point out the importance of the early diagnosis of giant cell arteritis (GCA) (Horton's disease). MATERIALS AND METHODS: a case report of a sudden bilateral blindness that had revealed GCA. CASE REPORT: A 68-year old female patient with a history of elevated blood pressure and diabetes mellitus type 2, was examined in emergency for a right painful headache developed one week previously. In ophthalmological examination, her BCVA was 0.9 and P2 in both eyes. Diagnosis of Horton's disease was not initially done in spite of elevated erythrocytes sedimentation rate (ESR) at 30 mm, protein C reactive (CRP) at 19 mg/l. The patient consulted seven weeks later in emergency for a sudden bilateral blindness associated with severe headache, recent asthenia, and limping of the lower jaw. At that time, visual acuity was reduced to light perception in both eyes whereas ophthalmoscopy revealed a bilateral central retinal artery occlusion (CRAO). ESR was 74 mm and CRP 233 mg/I. Temporal artery biopsy confirmed the diagnosis of GCA. The patient was treated with systemic steroids without visual recovery. CONCLUSION: This case outlines the importance of the early diagnosis of GCA in order to make possible to start treatment before the occurrence of irreversible complications.

[Increase rate of ambulatory and management of the care path in breast cancer surgery]. / Augmentation du taux de prise en charge ambulatoire et organisation du parcours de soins en chirurgie sénologique.

OBJECTIVE: To describe practices and impact of ambulatory surgery rate, patient satisfaction after Nursing Support and Post Ambulatory Follow-up Device at Home at the Henri Becquerel Center (DIASPAD CHB) has been set up during surgical management in breast cancer. METHOD: This is a prospective monocentric observational study carried out between January 2017 and December 2018. Patients eligible for the study should undergone breast cancer surgery without reconstruction. Outpatient care was possible if patients met medical, surgical, psychosocial and environmental criteria according to the characteristics of the foreseeable operating suites. We evaluated the progression of the ambulatory hospitalization rate since the DIASPAD CHB beginning and compared the use of this device in conventional and ambulatory hospitalization. RESULTS: Since January 2017, 1312 patients undergone breast cancer surgery without reconstruction. After DIASPAD CHB implementation, ambulatory surgery rate increased from 46 % to 81.7 % for patients operated for breast cancer. The satisfaction rate of patients and nurses was 99 %. CONCLUSION: DIASPAD CHB enabled ambulatory care to take a important share in surgical care in breast cancer by ensuring collaboration between healthcare professionals, anticipation, programming and coordination of care.

Development and characterisation of a new model of rat trophoblasts.

The placenta plays a key role during pregnancy. In vitro models have proven to assess the role of placental transporters in the exchange of nutrients, waste products and the distribution of drugs between the maternal and fetal compartments. Therefore, a primoculture of Wistar rat trophoblasts from the labyrinth zone was developed and characterised. Expression of placental transporters including P-glycoprotein (P-gp) and bcrp was evaluated by western blot and their activity using different inhibitors. A time-dependent increase in P-gp expression was noted from primocultures Day 2 to Day 4 followed by a plateau thereafter, whereas bcrp expression was stable throughout the culture period. P-gp and bcrp expression was maintained after seven passages in primocultures and in cryopreserved trophoblasts (up to 3 freezings and 10 passages). Activity of efflux transporters was confirmed in both placental primocultures and cryopreserved trophoblasts by an approximately 60% inhibition with cyclosporin A and valspodar for P-gp and 55% with elacridar for bcrp. In sum, this new in vitro model seems promising for a better understanding of the role of P-gp and bcrp in the toxicity of drugs during pregnancy and could be considered as an additional step towards the minimization of animal testing during drug development.

[Limitations of breast reconstruction using exclusive lipofilling: A retrospective study over 10 years]. / Limites de la reconstruction mammaire par lipofilling exclusif : étude rétrospective sur 10 ans.

OBJECTIVES: The primary objective was to assess the failure rate of exclusive lipofilling breast reconstruction. The secondary objectives were the identification of failure predictive factors of exclusive lipofilling breast reconstruction and the early complications. METHODS: We performed a retrospective study in Normandy analysing cases of secondary breast reconstruction by exclusive lipofilling after radical mastectomy, from January 2006 to December 2016. We compared a group of patients who completed exclusive lipofilling breast reconstruction (n=22) with a group of patients who underwent other techniques of breast reconstruction (n=16). RESULTS: The failure rate of breast reconstruction by exclusive lipofilling was 32.6%. Need of adjuvant chemotherapy treatment was associated with a higher failure rate than exclusive lipofilling breast reconstruction (81.2% vs. 45.5%, P<0.05). The age of patients was significantly higher in case of reconstruction failure (45.2 vs. 50.9 years mean age, P<0.05). Need of adjuvant radiotherapy treatment was not associated with a higher failure rate than exclusive lipofilling breast reconstruction. The main complications were cutaneous burn due to cannula and haematoma at the donor site (11/22) and breast haematoma (11/22). CONCLUSIONS: Informing patients of the risk of breast reconstruction failure due to the high adipocytes resorption, is necessary when patients are undergoing exclusive lipofilling breast reconstruction. A prospective study with greater workforce is needed to shore these results and assess postoperative complications.

P-glycoprotein expression of the human placenta during pregnancy.

OBJECTIVE: To investigate whether the placental expression of P-glycoprotein shows a quantitative difference during pregnancy. STUDY DESIGN: Villous tissue was collected from chorionic villus samples (13-14 weeks of gestation; n = 3 and 20-25 weeks of gestation; n = 4) and from full-term placentas (38-41 weeks of gestation; n = 28). P-glycoprotein was detected by western blot analysis and quantified by densitometry. RESULTS: We showed for the first time a significant and progressive two-fold decrease in the mean expression of P-glycoprotein between early and late samples, with a major overlap of values. CONCLUSION: As P-glycoprotein appears to be involved in drug extrusion, these data suggest that the placenta's ability to protect the fetus from xenobiotics is greater in early pregnancy than at term.

Effect of acute oral administration of alcohol on superoxide anion production from mouse alveolar macrophages.

The production of superoxide anions (superoxide) from alveolar macrophages stimulated or not with opsonized zymosan was investigated in the mouse after acute oral administration of alcohol (6.5 g/kg). Superoxide production was assayed using a nitroblue tetrazolium (NBT) reduction and chemiluminescence assay. In the absence of opsonized zymosan, superoxide concentration was not affected 1 h after ethanol treatment but was significantly increased 15 and 24 h after treatment. In the presence of opsonized zymosan, a biphasic response was observed. Superoxide production was significantly reduced 1 and 3 h after administration but was increased 15 and 24 h after treatment. One hour after treatment, the percentage of cells that phagocytized opsonized zymosan and reduced NBT was significantly decreased, whereas 24 h after alcohol treatment, phagocytosis was normal and the percentage of cells reducing NBT was significantly increased. The activity of cytosolic superoxide dismutase from alveolar macrophages was not altered 1 h after administration but was significantly reduced 24 h later. Considering the functions of alveolar macrophages in the defense of the lung, these alterations in the production of reactive oxygen species after ingestion of alcohol could explain why alcoholics are more sensitive to pulmonary infections.

Separation of red blood cells by field flow fractionation.

Field flow fractionation (FFF) is a new methodology described as being well-suited for the separation and characterization of biopolymers and particles. On theoretical grounds, cells may be separated with FFF if they differ in size, density or deformability. In the present study, we first tried to determine optimal separation conditions for red blood cells; thereafter we used FFF to examine red cell changes during a phenylhydrazine-induced hemolytic anemia. It has been shown that in less than 30 minutes, FFF is able to separate normal red blood cells from Heinz body-rich cells or reticulocytes that differ in size or density. The successive steps of hemolysis and regeneration appear clearly on the fractograms. Advantages and drawbacks of the method are discussed.

Prenatal diagnosis of HIV infection: two attempts using fetal blood sampling.

Blood samples were studied, prior to medical terminations of pregnancy, in two second trimester fetuses with HIV-positive mothers. Fetal blood was obtained from the umbilical vein under ultrasound guidance. No evidence of infection was found in either fetus. In particular, lymphocyte subpopulations were at normal levels and cultures yielded no reverse transcriptase activity. Postmortem findings were normal. Reliable means for prenatal diagnosis of HIV infection, with a minimal risk of false-negative results, have yet to be developed. However, further studies using fetal blood sampling should be useful for the management of HIV-positive pregnancies.

Absence of transplacental passage of pentosan polysulfate during mid trimester of pregnancy.

Eight women who were going to have an abortion between the 18th and 23 week of gestation for chromosomal abnormalities or haemoglobinopathies received intravenously 50 mg of pentosan polysulfate (PSP). Maternal results of haemostasis prior and after the injection of the drug were compared. Fetal coagulation parameters were tested on samples obtained by direct puncture of the umbilical cord under ultrasound guidance, 30 min after injection. Results were compared to those of normal fetuses at the same stage of gestation, obtained in the same conditions. In mothers' plasma, 30 min after injection, APTT was prolonged, factor Xa generation was markedly impaired, and factor V level was deeply decreased. By contrast, no modifications of these parameters were observed in fetal plasma, 30 min after the injection of PSP to their related mothers when compared to control fetuses. Thus the absence of biological modifications induced by PSP injection could demonstrate that this drug does not cross through the placenta.

Vitamin K dependent proteins in fetal hemostasis at mid trimester of pregnancy.

The vitamin K dependent coagulation factor activities were measured in 63 normal human fetuses from 19 to 28 weeks of pregnancy. These activities were included between 9 to 28 percent of normal adult levels. Prothrombin antigen, factor IX antigen and protein C were also measured. There is a good correlation between prothrombin procoagulant activity and antigenicity, suggesting that low level of these vitamin K dependent proteins in fetuses is probably a consequence of liver immaturity.

Placental transfer of vitamin K1 and its implications in fetal hemostasis.

Vitamin K status was evaluated using coagulation studies and/or vitamin K1 assays in a total of 53 normal fetuses and 47 neonates. Second trimester fetal blood samples were obtained for prenatal diagnosis under ultrasound guidance. Endogenous vitamin K1 concentrations (determined by high performance liquid chromatography) were substantially lower than maternal levels. The mean maternal-fetal gradient was 14-fold at mid trimester and 18-fold at birth. Despite low vitamin K levels, descarboxy prothrombin, detected by a staphylocoagulase assay, was elevated in only a single fetus and a single neonate. After maternal oral supplementation with vitamin K1, cord vitamin K1 levels were boosted 30-fold at mid trimester and 60-fold at term, demonstrating placental transfer. However, these levels were substantially lower than corresponding supplemented maternal levels. Despite elevated vitamin K1 concentrations, supplemented fetuses and neonates showed no increase in total or coagulant prothrombin activity. These results suggest that the low prothrombin levels found during intrauterine life are not due to vitamin K deficiency.

Measurement of low molecular weight heparin ex vivo activities in clinical laboratories using various anti-Xa assays: interlaboratory variability and requirement for an agreed low molecular weight heparin standard.

The only sensitive and convenient assay to assess the biological activity of low molecular weight heparins (LMWHs) is based on the potentiation of activated factor Xa inhibition. Several procedures for measuring the socalled anti Xa activity have been proposed. In this collaborative study including eight laboratories, we have used four different assays (three amidolytic and one clotting based methods) for measuring the anti Xa activity of ex vivo samples obtained after injecting three different LMWHs. The dispersion of the results obtained by calibration against standard heparin could be reduced by using any of the three LMWHs for calibration. A coefficient of variation less than 0.20 between values obtained in different laboratories using a variety of methods seems acceptable. However it is necessary to refer to a common international standard for expressing the results in units and to define, for each of the three products, the therapeutic range.

High levels of circulating thrombomodulin in human foetuses and children.

Thrombomodulin (TM) is an endothelial cell surface proteoglycan with anticoagulant functions, also implicated in cell proliferation, cell-cell adhesion and differentiation. In this study we determined circulating plasma TM (pTM) levels in human foetuses at different stages of pregnancy, at birth and in childhood. TM levels increased with gestational age, the median level reaching a peak of approximately 165 ng/ml between the 23rd and 26th week, thereafter decreasing gradually, reaching a value of 108 ng/ml at birth. pTM continues to decrease progressively during childhood, reaching in the 5-15 years group a median of 56 ng/ml which approaches the adult value. The pTM peak was statistically significant and represents a specific foetal phenomenon as it was independent of the corresponding maternal values. As a whole, the pTM pattern during foetal maturation appears totally different from that of protein C, prothrombin and other coagulation activators and inhibitors and thus, TM may play in the foetus another role in addition to its well-known anticoagulant function.

Characterization of mononuclear cell subpopulations in normal fetal peripheral blood.

It is now possible to characterize fetal peripheral blood mononuclear cells (FPBMC) from normal fetuses sampled in utero under ultrasound guidance. The surface phenotype of FPBMC from 25 fetuses, between the 20th and the 26th week of gestation, was studied using standard reagents that are known to delineate mononuclear cell subsets in adult peripheral blood. Results were compared with those obtained in neonates (cord blood) and adults. The major subsets of adult PBMC are represented in fetal blood with few qualitative differences: 20% of FPBMC are not recognized, the percentage of T cells is lower with a higher ratio T4/T8, the fraction of cells that express DR molecule is very high, and the distribution of NK antigens is different in fetuses. B cells and monocytes are in equal proportion. This work represents a prerequisite for future functional studies, and provides normal fetal values that will be useful for prenatal diagnosis of congenital immunodeficiency.

Toxoplasma gondii infection during pregnancy: T lymphocyte subpopulations in mothers and fetuses.

Prenatal diagnosis of fetal toxoplasmosis is possible with the use of fetal blood sampling, amniocentesis and ultrasound examination. The purpose of this study was to describe T lymphocyte subsets (CD3, CD4 and CD8) in mothers and their fetuses when Toxoplasma gondii infection occurred during pregnancy. Maternal and fetal blood samples were obtained in 86 cases and 9 fetuses showed T. gondii infection. Control groups consisted of 30 healthy nonpregnant women and 30 pregnant women. Pregnant women with T. gondii infection showed an increase in the suppressor (CD8) T subpopulation and a significant depression in the total helper (CD4) T cells. These alterations were more important in mothers whose fetus was infected. We showed the progressive maturation of the fetal immune system with a regular increase of all T lymphocyte subsets. Marked alterations were observed in the 9 infected fetuses (depression of CD4 population and lower CD4/CD8 ratio). In the future these differences might be used as a new marker of the severity of fetal lesions and become a useful diagnostic tool.

Role of interferon, antibodies and macrophages in the protective effect of Corynebacterium parvum on encephalomyocarditis virus-induced disease in mice.

Treatment of mice with Corynebacterium parvum enhances their resistance to encephalomyocarditis (EMC) virus infection. In EMC-virus-infected mice, pretreated with C. parvum, neither interferon production nor antibody responses were increased. A decrease of virus recovery was observed in cultures of macrophages taken from the peritoneum of mice early after injection of C. parvum and infected with EMC-virus in vitro. The data suggest that C. parvum acts by increasing intrinsic antiviral activity of macrophages.

Preparation and analysis of fetal liver extracts.

The aim of this work is to describe the techniques that have been used for preparation and analysis of whole fetal liver extracts destined for in utero transplantation. Nine fetal livers between 12 and 17 weeks of gestation were prepared: cell counts and assessment of the hematopoietic cell viability were performed on cell suspensions. Hepatocytes represented 40 to 80% of the whole cell population. The remaining cells were constituted by hematopoietic cells (mainly erythroblasts), as well as by endothelial cells. The latter expressed CD34 on their surface, interfering with the assessment of CD34+ hematopoietic cells by flow cytometry. Direct visual morphologic control using alkaline phosphatase anti-alkaline phosphatase techniques was needed to differentiate hematopoietic from extra-hematopoietic CD34+ cells. Between 3.0 and 34.6 x 10(6) CD34+ viable hematopoietic cells were collected per fetal liver. Adequate differentiation of these cells into burst-forming units erythroid (BFU-E), colony-forming units granulocyte-macrophage (CFU-GM), and colony-forming units granulocyte erythroid macrophage megakaryocyte (CFU-GEMM) has been shown for each sample in clonogeneic cultures. In conclusion, fetal liver is a potential source of hematopoietic stem cells. Their numeration, based on the presence of CD34, is hampered by the expression of this antigen on other cells contained in the liver cell extract, in particular endothelial cells.

Low-dose aprotinin is ineffective to treat excessive bleeding after cardiopulmonary bypass.

BACKGROUND: Uncontrolled clinical experience at our institution suggested that low-dose aprotinin could control excessive bleeding after cardiopulmonary bypass (CPB). A randomized clinical trial was conducted to determine the efficacy of low-dose aprotinin in the treatment of hemorrhage after cardiac surgery. METHODS: One hundred seventy-one patients undergoing cardiac surgery with CPB were included. Forty-four patients (26%) bled significantly in the intensive care unit (>100 mL/h) and received either aprotinin (200,000 KIU bolus + 100,000 KIU/h for 8 hours) or placebo in addition to our standard management of excessive bleeding. RESULTS: Median bleeding before study drug administration was not different between aprotinin (200 mL) and placebo (212.5 mL) groups. Bleeding decreased significantly with time and similarly in both groups. Ninety-five percent of patients required transfusions in both groups. Median blood products transfused were 13 and 8 units per patient in the aprotinin and placebo groups respectively (p = NS). CONCLUSIONS: Routine administration of low-dose aprotinin as part of the treatment protocol to control hemorrhage after CPB does not reduce bleeding or transfusion requirements and, therefore, cannot be recommended.

Inhibition of platelet aggregation by abciximab but not by aspirin can be detected by a new point-of-care test, the hemostatus.

We have investigated the type of platelet defect that can be detected with the Hemostatus test performed with the Hepcon/HMS instrument (Medtronic) designed to investigate platelet function during and after surgery. This assay is based on the comparison of the activated clotting time of whole blood measured in cartridges containing kaolin or kaolin and platelet-activating factor in different concentrations. Addition of platelet-activating factor shortened the blood activated clotting time when the platelet counts were normal. However, when platelet counts were below 70000/microL, the activated clotting time was prolonged in all channels including those without platelet-activating factor showing the influence of platelets in the formation of the clot under the conditions tested. Inhibition of platelet aggregation with c7E3 (abciximab, ReoPro) also induced a much-prolonged activated clotting time, and a similar finding was seen with blood from a patient with Glanzmann's thrombasthenia confirming the need for platelet aggregation and/or the glycoprotein (GP) IIb-IIIa complex. In contrast, the interaction of GP Ib with von Willebrand Factor was not of major importance, since inhibition of this interaction with the anti-GP Ib murine monoclonal antibody, ALMA-12, did not modify the activated clotting time. Furthermore, the activated clotting time measured for patients with an acquired defect in von Willebrand Factor activity were unchanged. Finally, inhibition of thromboxane A2 formation by aspirin did not influence the results of this test. Globally, the Hemostatus test was able to detect major abnormalities of GP IIb-IIIa function in the presence or absence of platelet-activating factor.