Implementation of epidural analgesia for labor: is the standard of effective analgesia reachable in all women? An audit of two years.

BACKGROUND: Social and cultural factors combined with little information may prevent the diffusion of epidural analgesia for pain relief during childbirth. The present study was launched contemporarily to the implementation of analgesia for labor in our Department in order to perform a 2 years audit on its use. The goal is to evaluate the epidural acceptance and penetration into hospital practice by women and care givers and safety and efficacy during childbirth. PATIENTS AND METHODS: This audit cycle measured epidural analgesia performance against 4 standards: (1) Implementation of epidural analgesia for labor to all patients; (2) Acceptance and good satisfaction level reported by patients and caregivers. (3) Effectiveness of labor analgesia; (4) No maternal or fetal side effects. RESULTS: During the audit period epidural analgesia increased from 15.5% of all labors in the first trimester of the study to 51% in the last trimester (p < 0.005). Satisfaction levels reported by patients and care givers were good. A hierarchical clustering analysis identified two clusters based on VAS (Visual Analogue Scale) time course: in 226 patients (cluster 1) VAS decreased from 8.5±1.4 before to 4.1±1.3 after epidural analgesia; in 1002 patients (cluster 2) VAS decreased from 8.12±1.7 before (NS vs cluster 1), to 0.76±0.79 after (p < 0.001 vs before and vs cluster 2 after). No other differences between clusters were observed. CONCLUSIONS: Present audit shows that the process of implementation of labor analgesia was quick, successful and safe, notwithstanding the identification of one cluster of women with suboptimal response to epidural analgesia that need to be further studies, overall pregnant womens'adhesion to labor analgesia was satisfactory.

Management of high-quality dehydrated grape in vinification to produce dry red wines.

Grape controlled dehydration of "Cesanese" and "Sangiovese" wine grapes, followed by an innovative vinification protocol, was studied. Fresh grapes of both varieties were processed into basic wines (IW = initial wine). 'Cesanese' must from pressed dehydrated grapes (solid and liquid) was directly added (15 and 30% v/v) into the IW activating a refermentation. 'Sangiovese' must (solid and liquid) from pressed dehydrated grapes was fermented and, when the wine reached 5% alcohol concentration, every day, the IW was added until a final concentration of 40 or 60% (v/v). The produced "blended wines" (BW) had significantly higher alcohol, glycerol, extract, and polyphenol concentration. Malolactic fermentation was completely ended in all BW with no malic acid and formation of lactic acid (0.5-1 g/L). All wines showed a significant higher concentration in 4-vinylguaiacol, acetovanillone, and 3-oxo-α-ionol, providing spicy and fruity notes at the sensory analyses, and being appreciated for their body balance, less acidity, and flavor intensity.

Three-dimensional computational model of a blood oxygenator reconstructed from micro-CT scans.

Cardiopulmonary bypass procedures are one of the most common operations and blood oxygenators are the centre piece for the heart-lung machines. Blood oxygenators have been tested as entire devices but intricate details on the flow field inside the oxygenators remain unknown. In this study, a novel method is presented to analyse the flow field inside oxygenators based on micro Computed Tomography (µCT) scans. Two Hollow Fibre Membrane (HFM) oxygenator prototypes were scanned and three-dimensional full scale models that capture the device-specific fibre distributions are set up for computational fluid dynamics analysis. The blood flow through the oxygenator is modelled as a non-Newtonian fluid. The results were compared against the flow solution through an ideal fibre distribution and show the importance of a uniform distribution of fibres and that the oxygenators analysed are not susceptible to flow directionality as mass flow versus area remain the same. However the pressure drop across the oxygenator is dependent on flow rate and direction. By comparing residence time of blood against the time frame to fully saturate blood with oxygen we highlight the potential of this method as design optimisation tool. In conclusion, image-based reconstruction is found to be a feasible route to assess oxygenator performance through flow modelling. It offers the possibility to review a product as manufactured rather than as designed, which is a valuable insight as a precursor to the approval processes. Finally, the flow analysis presented may be extended, at computational cost, to include species transport in further studies.

Management of postharvest grape withering to optimise the aroma of the final wine: A case study on Amarone.

Amarone wine is different from regular dry wine due to the postharvest withering of Corvina, Corvinone and Rondinella grapes. Grapes were withered in a commercial facility with variability in terms of temperature and relative humidity (R.H.). Sugar content reached 230-240gL(-1) and 280gL(-1) at 20% and 30% mass loss, respectively. Most of VOCs (volatile organic compounds) decreased during withering but few VOCs increased during withering and we considered as markers; in Corvinone they were methylhexanoate, dimethylsuccinate, nerol, nonanoic acid, and benzyl alcohol; in Corvina, benzyl alcohol, isoamyl alcohol, 1-hexanol, p-cymen-8-ol, 2,3 pinanediol, 3-oxo-ionol and 3-methyl-1-pentanol, coumaran and damascenone; in Rondinella, hexanol, nonanoic acid, methyl vanillate, damascenone, 3-oxo-ionol, eugenol, p-cymen-8-ol, 2,3 pinanediol, coumaran and raspberry keton. Olfactive descriptors of the wines and the potential aroma of the combination of Corvina wine with the wines of the other two varieties at different percentages of mass loss are reported.

Cell-cycle progression and apoptosis in K562 and Molt-4 cells after cell-to-cell transmission of HTLV-I: modulation by interferons.

Human T-cell leukemia virus type I (HTLV-I) is mainly propagated by cell division and therefore the virus-driven proliferation of infected cells can represent a predisposing condition to final development of adult T-cell leukemia (ATL) in vivo. To correlate virus expression and cell cycle progression of recipient cells after acute infection with HTLV-I, K562 multipotent erytholeukemia and Molt-4 T-lymphoma cells were used as recipient cells in a cell-to-cell virus transmission model. Cell cycle progression was studied by flow cytometry during one duplication cycle of recipient cells and transcription of HTLV-I was evaluated during the same time course. The antiproliferative and antiviral effects of recombinant interferons alpha, beta and gamma were also evaluated on cell cycle progression and HTLV-I expression. Transcription of HTLV-I in immortalised virus-donor MT-2 T-cells was found to be related to cell cycle. After coculturing recipient K562 or Molt-4 cells with lethally irradiated, non-dividing virus-donor MT-2 cells, progression into cell cycle of recipient cells was delayed. A pre-G(1) peak, corresponding to 6-11 % apoptotic cells, was identified in cocultured Molt-4/MT-2 cells and not in Molt-4 controls, and was not affected by treatment with IFNs. Notably, no such peak was identified either in control or in cocultured K562 cells. During this time course, transcription of the viral subgenomic mRNA encoding for the env-pX region was prevalently observed. Treatment with IFNalpha and especially with IFNbeta at the onset of the cultures inhibited the growth of both control and virus-exposed recipient cells. IFNgamma was less effective. A clearcut reduction of the percentage of cells entering the S phase was observed only after treatment with IFNbeta. At the same time, in IFNbeta-treated cocultures a marked inhibition of transcription of viral mRNA was observed, suggesting that, during acute infection, treatment with IFNbeta contributes to reduce the infection of recipient cells by down-regulating both the cellular proliferation rate and virus transcription in infected cells.

Antiproliferative activity of cyclopentenone prostaglandins in early HTLV-1 infection is independent of IL-2 and is associated with HSP70 induction.

Cyclopentenone prostaglandins PGA1 and PGJ2 can inhibit the growth of HTLV-1 infected cord blood-derived human mononuclear cells (CBMC), both after acute infection and in chronically infected, immortalized cells. When CBMC were exposed to HTLV-1 infection by coculturing with lethally irradiated, virus-donor allogeneic MT-2 cells, they underwent a proliferative response, that peaked within the first week and then declined. PG treatment did not inhibit the initial proliferation (day 4) of cocultured CBMC, while multiple treatments with PGA1 and more efficiently with PGJ2, suppressed the late cell proliferation (from day 8 onward). The pharmacological effects of PGA1 and PGJ2 were reversible and therefore multiple treatments were required to maintain their antiproliferative activity. Increasing concentrations (20, 40, 80 IU/ml) of recombinant IL-2 did not affect the virus-associated proliferative response of CBMC, and exogenous IL-2 did not revert the antiproliferative effect of both PGs. Arrest of proliferation in cocultured CBMC occurred concomitantly with expression of high levels of HSP70 in the cells. In fact, though HSP70 expression was induced early (day 5) after exposure to HTLV-1, its expression was further increased after multiple PG treatments and high levels were found when the antiproliferative effect of PGs became manifest. Since HSP70 protein family is involved in the control of cell cycle as well as in antigen processing and presentation during the immune response against tumor cells and pathogens, the persistent expression of this protein in PG-treated cocultures suggested that, beside inhibiting the growth of virus-infected cells, HSP70 expression might play a role in modulating the immune function of CBMC. However, unlike in most virus infection models, in which cyclopentenone PGs exert clear antiviral effects by inhibiting the synthesis and maturation of virus proteins, no antiviral activity was found in this model of infection. This strongly suggests that the main effect of these PGs against HTLV-1 infected cells consists in inhibiting proliferation in vitro without affecting viral expression.

In vitro infection of leukemic bone marrow with HTLV-I generates immortalized cell lines expressing T or myeloid cell phenotype.

Leukemic bone marrow cells ( > 90% blasts) of a patient with acute myeloblastic leukemia (AML), non-treated or pretreated in vitro with a mutagenic triazene compound, were infected with HTLV-I by coculture with irradiated virus-donor cells. Immortalized, HTLV-I+, double-positive CD4/CD8 euploid T cell lines, expressing HLA class I/II monomorphic determinants, and inappropriate myeloid and progenitor cell markers (ie CD13, CD14, CD15 and CD33 antigens) were obtained. In one out of 10 triazene-pretreated samples, HTLV-I infection resulted in the appearance of a rapidly growing triploid cell line (ie MTLC1 line) showing: (1) myeloid but not lymphoid phenotype; (2) beta and delta T cell receptor in germline configuration; (3) integrated, complete and incomplete HTLV-I provirus genome (also detected in a number of MTLC1 clones); (4) a high percentage of cells positive for non-specific cross-reacting antigen (a CEA-related molecule present in myeloid cells) under the influence of gamma-interferon; (5) absence of HLA class I/II antigen expression; (6) absence of tax gene transcription. Blast cell proliferation was marginal or absent when leukemic marrow was not subjected to retroviral infection. These results show that exposure of leukemic bone marrow to HTLV-I can be followed by immortalization of T and myeloid cells. Although no data are available to establish whether tax expression played a role in the early phase of the immortalization process of MTLC1 line, tax gene product was not required for maintaining long-term growth of MTLC1 cells.

HSP70 production and inhibition of cell proliferation in Molt-4 T-cells after cell-to-cell transmission of HTLV-I: effect of PGA1.

Infection with HTLV-I is associated with leukemic transformation of mature CD4+ T lymphocytes. PGA1, a powerful inhibitor of tumour cell proliferation, can prevent the clonal expansion of HTLV-I-infected cells following acute infection of cord blood-derived mononuclear cells. Since the antiproliferative effect of PGA1 on HTLV-I transformed, chronically infected MT-2 cell line was associated with induction of HSP70, we have investigated the effect of PGA1 on cell cycle progression and HSP70 production in a leukemic T-cell line (Molt-4) shortly after exposure to HTLV-I in a cell-to-cell transmission model. Rate of cell proliferation and HSP70 expression were studied within one duplication cycle of Molt-4 cells after exposure to HTLV-I. Growth of both control and virus-exposed cultures was inhibited by treatment with PGA1 (4 micrograms/ml) and cell cycling was arrested preferentially at the G1/S interphase. Synthesis of HSP70 was induced within 3 h by PGA1 in control and virus-exposed Molt-4 cells and became undetectable from overnight onward, though the protein accumulated in the cells. The arrest of growth was observed from overnight up to 48 h so that treated cells almost missed one cycle. Interestingly, HSP70 transcript and protein persisted at remarkably high levels in Molt-4 cells exposed to HTLV-I in the absence of PGA1, showing that HSP70 expression can be directly activated during primary infection with this human retrovirus. Moreover, in these cocultures, treatment with PGA1 or heat shock was not able to increase further the elevated level of HSP70 found in untreated cocultures, suggesting that during the early period of the virus-transmission phase, HTLV-I could interfere with HSP70 induction by other inducers.

In-vitro differentiation of human monocytes into mature macrophages during long-term cultures.

A method is described which allows human peripheral blood monocytes from any given donor to differentiate in vitro into mature macrophages. About 90% of the starting monocytes are maintained during the long-term culture and are matured to macrophages. Thus cell loss is minimal and the resulting population of mature macrophages can be regarded as representative for all possible macrophage subpopulations present in peripheral blood. These cultures represent a standardized model for in-vitro studies on the role of mature macrophages in various immunological reactions.

Chemiluminescence of macrophages depends upon their differentiation stage: dissociation between phagocytosis and oxygen radical release.

The in vitro differentiation and maturation of resident and activated mouse and human macrophages (M phi) from different anatomical sources was investigated with regard to their oxygen metabolism during zymosan phagocytosis. We found evidence that chemiluminescence (CL) of M phi depends upon their differentiation stage: a) In the absence of any phagocytic stimulus, the human M phi showed a lucigenin-dependent CL background that was approximately 10-fold higher than in mouse M phi and decreased to low levels in resident M phi (monocyte-derived human M phi). This background was reduced by SOD to about 50%. No relevant luminol-dependent background was observed in all mouse and human M phi during culture time. b) Resident and activated mouse and human M phi could be distinguished in terms of their lucigenin-dependent CL during zymosan phagocytosis, which was persistently high in activated M phi, but decreased to comparatively low levels in resident M phi during culture time. This zymosan-elicited CL was almost completely SOD-dependent during all culture time. c) A dissociation between phagocytosis and oxygen radical release is observed: the decrease of both minolul and lucigenin-dependent CL in resident phagocytizing M phi during maturation did not correspond to a decrease of their phagocytic activity. Phagocytosis occurred at a high rate also in the absence of a relevant CL-detectable generation of oxygen radicals. The oxygen radical release, as measured by SOD-inhibitable cytochrome c reduction, paralleled CL during zymosan phagocytosis and declined with maturation of monocytes into M phi. In contrast, the zymosan-induced nitro-blue-tetrazolium reduction increased in mature resident human M phi. Thus, it seems that different metabolic pathways are utilized during phagocytosis in young and mature M phi.

Low concentrations of suramin can reduce in vitro infection of human cord blood lymphocytes with HTLV-I during long-term culture.

In vitro infection of human cord blood lymphocytes (CBL) with human T-cell leukemia/lymphoma virus type I (HTLV-I) was found to be reduced by suramin treatment at a concentration ranging from 10-100 micrograms/ml. At higher concentrations (500 micrograms/ml) suramin was toxic to the cells and even resulted in an increased percentage of cells positive for the p19 viral core protein. Suramin treatment at the onset of the CBL coculture with a lethally irradiated HTLV-I donor cell line (MT-2) reduced virus transmission, evaluated as number of p19+ cells, and the consequent amount of integrated provirus in the host genome. The amount of viral RNA transcripts was not reduced in CBL cocultures. On the other hand, suramin affected HTLV-I replication in infected MT-2 cells, when used at a concentration of 50 micrograms/ml, and this might contribute to the reduced infectivity of suramin-treated MT-2 cells. In addition to its antiviral effects, suramin exerted a modest positive regulation on the natural killing activity of CBL and their early proliferative response in mixed lymphocyte/tumor cell culture.

Quality of data in multiethnic health surveys.

OBJECTIVE: There has been insufficient research on the influence of ethno-cultural and language differences in public health surveys. Using data from three independent studies, the authors examine methods to assess data quality and to identify causes of problematic survey questions. METHODS: Qualitative and quantitative methods were used in this exploratory study, including secondary analyses of data from three baseline surveys (conducted in English, Spanish, Cantonese, Mandarin, and Vietnamese). Collection of additional data included interviews with investigators and interviewers; observations of item development; focus groups; think-aloud interviews; a test-retest assessment survey; and a pilot test of alternatively worded questions. RESULTS: The authors identify underlying causes for the 12 most problematic variables in three multiethnic surveys and describe them in terms of ethnic differences in reliability, validity, and cognitive processes (interpretation, memory retrieval, judgment formation, and response editing), and differences with regard to cultural appropriateness and translation problems. CONCLUSIONS: Multiple complex elements affect measurement in a multiethnic survey, many of which are neither readily observed nor understood through standard tests of data quality. Multiethnic survey questions are best evaluated using a variety of quantitative and qualitative methods that reveal different types and causes of problems.

Making the case for cancer prevention in the schools.

Advances in scientific research indicate school-based cancer prevention programs could substantially reduce the risk that children and youth will develop cancer in later life. Nevertheless, scientific evidence alone cannot make a winning case for cancer prevention in schools. This programmatic emphasis must be justified in relation to the school's role in achieving national health objectives and concepts of comprehensive health education. Problems in implementing school health education also must be addressed, but this will require confronting fundamental value conflicts concerning the mission of schools in American society. After examining these issues, the author concludes that the case for school-based cancer prevention can best be advanced through collaboration with others who share a commitment to children and youth, but who differ in their specific concerns and agendas.

Unplanned nutrition education in the schools: sugar in elementary reading texts.

Analysis of food content in 1,666 readers, prereaders and reading workbooks for grades K-3 revealed an undue emphasis upon sweets in both words and pictures. Cake alone accounted for one of every 12 food appearances. While fruits and vegetables were pictured slightly more often than sugar-rich foods, they were related to actual food consumption far less frequently than sweets. By publisher, other food groups accounted for 10% or less of all food pictures and 15% or less of all food words. Snacks, treats and parties appeared more often as occasions for eating than regular meals, excluding picnics. Families were rarely presented eating together and little attention was devoted to the nutritional value of food. Knowledge children acquire from the media and other sources before attending school has been identified as a force counteracting nutrition education, but unintended messages conveyed in K-3 readers also may work against the promotion of healthy eating habits. Reading texts should be screened for nutritional content before adoption and revised to reduce the appearance of sweets in accord with national dietary goals. Nutrition education must extend beyond teaching the basic four food groups to help children recognize how their food choices are affected by environmental influences, inside as well as outside of school.

Role of biological response modifiers in immunochemotherapy of solid tumors and retroviral-induced leukemia.

Modulation of the immune response by the use of biological response modifiers (BRM) is aimed at amplifying the host resistance against cancer. Studies on inhibition of tumor growth on an in vitro model, in which human breast carcinoma (HBL-100) and human lung carcinoma (H125) cells were used as target tumor cells, confirmed that interferons (IFNs) alpha and beta can amplify the antineoplastic effects of immunochemotherapy by enhancing the cytotoxic activity of effector cells and by antagonizing the immunodepressive effects of radiation or anticancer drugs. Moreover, data obtained from a pilot clinical trial, designed to test the effect of low concentrations of beta-IFN on natural cell-mediated cytotoxicity, pointed out a good correlation between the in vitro and in vivo responsiveness to beta-IFN in cancer patients. The immunomodulating and antiproliferative effects of BRM were also evaluated in a model of viral leukemogenesis in vitro, after infection of cord blood derived mononuclear cells (CB-MNC) with the human leukemic retrovirus HTLV-I. Alpha-and beta-IFN were previously shown to regulate differentially the antiviral competence of recipient CB-MNC, by interfering with viral replication and delaying the emergence of the transformed clone(s). One of the mechanisms of IFN action that contributes to control HTLV-I infection in vitro can be ascribed to their property of partially counteracting the depression of cell-mediated cytotoxicity that follows exposure to HTLV-I. In the light of data previously and herein described, it seems that alpha- and beta-IFN can be considered potential candidates to define combined therapy with antiviral drugs, to control the early stages of retrovirus-associated disease in human pathology.

Differential interference of alpha, beta or gamma interferons with HTLV-I integration and expression in vitro.

Alpha, beta and gamma interferons (IFNs) can exert a powerful and direct antiviral activity against HTLV-I and can also modulate positively some cell-mediated immune functions of the host cell. These multiple effects of IFNs can induce a long-lasting inhibition of viral infection in recipient cells, probably by "priming" the host cell to an active antiviral competence. It has to be underlined that each IFN was active differentially on the replicative cycle of HTLV-I, thus suggesting the possibility of a complementary action of IFNs in inhibiting HTLV-I infection. This might be relevant to a possible therapeutical approach for prevention of HTLV-I related diseases.

[Etiopathogenesis and therapeutic trends in adult T-cell leukemia associated with HTLV-I retrovirus]. / Eziopatogenesi e prospettive terapeutiche nella leucemia a cellule T mature associata al retrovirus HTLV-I.

HTLV-I (Human T-cell leukemia virus type I) has been the first human retrovirus identified and then associated with a definite pathological entity, a leukemic syndrome that specifically affects mature T-lymphocytes (ATL, adult T-cell leukemia), expressing CD3+, CD4+, CD8-, CD11- phenotype. This form of leukemia/lymphoma is endemic in southwestern islands of Japan, although at present the number of HTLV-I seropositive individuals has greatly increased, with a worldwide diffusion, following the expansion wave of the AIDS-associated HIV retrovirus. In fact, double seropositivity for both HIV and HTLV is frequently found among intravenous drug users. Although ATL leukemia or lymphoma occurs with a low frequency among HTLV-I seropositive individuals, it is likely that the evolution from a latent phase of infection to acute leukemia could be favoured by depression of immunosurveillance levels in the host. Therefore, special attention is required to prevent the diffusion of this retrovirus in adults, taking into consideration that newborn babies from seropositive mothers have to be considered at high risk for development of HTLV-I associated disease, on the basis of their immature immunocompetence.

Theory and the empowerment of health education practitioners.

Both the nature of theory and the way it is taught can overpower health education practitioners. As a consequence, myths which maintain theory and practice in separate realms may develop. This paper argues that to remedy this situation, practitioners must be helped to gain greater control of theory. Specific suggestions for accomplishing this goal are offered in a three-part prescription. First, concepts and teaching methods are introduced to dismantle myths about theory and to help practitioners understand its origins, nature, and functions. Second, health educators are encouraged to acknowledge limitations in theories currently guiding their practice. Third, they are shown ways they can exert leadership in developing theory to fill these gaps and build a more adequate knowledge base for confronting contemporary practice problems. Through this exercise of power, health educators will gain control over theory and expand the boundaries of practice, while also enhancing their professional status.