Ozonation of hospital raw wastewaters for cytostatic compounds removal. Kinetic modelling and economic assessment of the process.

The kinetics of the ozone consumption for the pretreatment of hospital wastewater has been analysed in order to determine the reaction rate coefficients between the ozone and the readily oxidisabled organic matter and cytostatic compounds. The wastewater from a medium size hospital was treated with ozone and peroxone methodologies, varying the ozone concentration, the reaction time and the hydrogen peroxide doses. The analysis shows that there are four cytostatic compounds, i.e. irinotecan, ifosfamide, cyclophosphamide and capecitabine, detected in the wastewaters and they are completely removed with reasonably short times after the ozone treatment. Considering the reactor geometry, the gas hydrodynamics, the mass transfer of ozone from gas to liquid and the reaction of all oxidisable compounds of the wastewater it is possible to determine the chemical ozone demand, COzD, of the sample as 256mgO3L(-1) and the kinetic rate coefficient with the dissolved organic matter as 8.4M(-1)s(-1). The kinetic rate coefficient between the ozone and the cyclophosphamide is in the order of 34.7M(-1)s(-1) and higher for the other cytostatics. The direct economic cost of the treatment was evaluated considering this reaction kinetics and it is below 0.3€/m(3) under given circumstances.

Primary and locally recurrent retroperitoneal soft-tissue sarcoma: local control and survival.

AIM: To evaluate local control for long-term prognosis in retroperitoneal soft-tissue sarcoma (primary tumors (PT) and local recurrence (LR)). METHODS: A total of 110 patients underwent surgery between 1988 and 2002. Prospectively gathered clinicopathological data were analyzed. Kaplan-Meier estimations and Cox regression analyses were performed. RESULTS: Resectability was 90%, being comparable for PT (n=71) and LR (n=39). Morbidity, mortality, blood loss, and operation time did not differ for PT or LR (24% vs. 31%, p=0.41; 7.0% vs. 5.1%, p=1.0; 1000 ml vs. 1500 ml, p=0.17; 240 min vs. 255 min, p=0.13). Hospitalization was comparable in both groups (median, 12 days (PT) and 13 days (LR)). Follow-up was 89 months (median, IQR 37-112 months). Local 3- and 5-year control rates after complete resection of PT were 66% and 59% (19% and 9% for LR, p<0.001). The mean number of operations were 1.4 for PT and 2.4 for LR (p=0.0047). The 5-year survival rates after complete resection were 51% for PT and 43% for LR (p=0.39). The 5-year survival rates were 65%, 4%, and 0% for complete resection, incomplete resection, and exploration, respectively (p<0.001). Multivariate analysis showed high-grade and blood loss with a poor prognosis. CONCLUSIONS: Comparable resectability rates and perioperative outcome were observed for surgery of PT and LR. Consequent reoperation leads to respectable long-term survival rates after resection of LR. The prognosis in retroperitoneal sarcomas varies significantly according to resectability, grade and blood loss.

Caracterización de los trabajadores cesantes en Colombia en el periodo 1992-2002, como fundamento para el diseño de una estrategia organizativa y financiera para la sostenibilidad de su aseguramiento en salud / Characterization of the unemployed workers in Colombia during the period 1992-2002 as a base for the design of an organizational and financial strategy for their sustainable health insurance

Uno de los obstáculos que ha tenido Colombia para lograr el objetivo de la Ley 100 de 1993 de universalizar el aseguramiento en salud ha sido el alto nivel de desempleo durante toda la década trascurrida desde entonces. Los trabajadores cesantes (aquellos que han tenido historia de vinculación laboral y que han perdido su empleo) constituyen con sus familias una población que en alto porcentaje carece de aseguramiento en salud, con lo cual queda expuesta al riesgo de pérdida del patrimonio familiar cuando alguno de sus integrantes se vea precisado a demandar atención que debe financiarse con los propios recursos. Objetivo: esta investigación se propuso precisar las características socioeconómicas y del aseguramiento en salud de los trabajadores cesantes, así como los ritmos temporales de empleo-desempleo en el país, buscando que sus resultados sirvan de base para el desarrollo de una segunda fase que diseñará y validará una estrategia de intervención para garantizar la sostenibilidad de su aseguramiento. Metodología: se trató de una investigación descriptiva-retrospectiva que utilizó técnicas de análisis cuantitativo. La información se obtuvo de bases de datos oficiales del gobierno colombiano y de estudios previos que tienen relación con el tema. Resultados: los resultados muestran una creciente participación de los trabajadores cesantes dentro del conjunto de la población desempleada del país, destacándose que una alta proporción de ellos (56,0 por ciento) han accedido a la educación media y que un alto porcentaje (58,7 por ciento) pertenecen al estrato socioeconómico medio. También resalta que la duración media del tiempo de cesantía pasó de 27,5 semanas en 1992 a 58,2 semanas en el año 2002.

Evaluation of F18-deoxyglucose positron emission tomography (FDG-PET) to assess the nature of neurogenic tumours.

AIMS: Benign neurofibromas and malignant peripheral nerve sheath tumours (MPNST) commonly develop in patients with neurofibromatosis. Differentiation of benign from malignant tumours by conventional preoperative imaging is unreliable. FDG-PET is a non-invasive technique for biological tumour evaluation. The aim of this study was to assess the value of FDG-PET in patients with neurogenic tumours suspicious for MPNST. METHODS: Benign and malignant neurogenic soft tissue tumours were prospectively evaluated by computed tomography or magnetic resonance imaging. Three-dimensional qualitative and quantitative FDG-PET was performed. Standard uptake value (SUV) was analyzed with respect to histological diagnosis and follow-up data. RESULTS: Twenty-five neurogenic soft tissue tumours were included. FDG-PET identified all primary (n=6) and recurrent MPNST (n=7). Benign lesions (n=12) did not demonstrate high FDG uptake. The SUV was significantly higher in MPNST (median 2.9; range 1.8-12.3), than in benign tumours (median 1.1; range 0.5-1.8) (p<0.001). At a cut-off value of 1.8 SUV measured 1 h post-injection FDG-PET distinguished between MPNST and benign neurogenic tumours with 100% sensitivity and 83% specificity. CONCLUSIONS: FDG-PET allows discrimination of benign from malignant neurogenic tumours. This should be particularly useful in patients with neurofibromatosis as FDG-PET may help to avoid multiple surgical procedures for benign tumours.

The glycogen-bound polyphosphate kinase from Sulfolobus acidocaldarius is actually a glycogen synthase.

Inorganic polyphosphate (polyP) is obtained by the polymerization of the terminal phosphate of ATP through the action of the enzyme polyphosphate kinase (PPK). Despite the presence of polyP in every living cell, a gene homologous to that of known PPKs is missing from the currently sequenced genomes of Eukarya, Archaea, and several bacteria. To further study the metabolism of polyP in Archaea, we followed the previously published purification procedure for a glycogen-bound protein of 57 kDa with PPK as well as glycosyl transferase (GT) activities from Sulfolobus acidocaldarius (R. Skórko, J. Osipiuk, and K. O. Stetter, J. Bacteriol. 171:5162-5164, 1989). In spite of using recently developed specific enzymatic methods to analyze polyP, we could not reproduce the reported PPK activity for the 57-kDa protein and the polyP presumed to be the product of the reaction most likely corresponded to glycogen-bound ATP under our experimental conditions. Furthermore, no PPK activity was found associated to any of the proteins bound to the glycogen-protein complex. We cloned the gene corresponding to the 57-kDa protein by using reverse genetics and functionally characterized it. The predicted product of the gene did not show similarity to any described PPK but to archaeal and bacterial glycogen synthases instead. In agreement with these results, the recombinant protein showed only GT activity. Interestingly, the GT from S. acidocaldarius was phosphorylated in vivo. In conclusion, our results convincingly demonstrate that the glycogen-protein complex of S. acidocaldarius does not contain a PPK activity and that what was previously reported as being glycogen-bound PPK is a bacterial enzyme-like thermostable glycogen synthase.

Assessment of soft tissue lesions suspicious for liposarcoma by F18-deoxyglucose (FDG) positron emission tomography (PET).

BACKGROUND: F18-deoxyglucose (FDG) positron emission tomography (PET) is a promising imaging technique. The aim of this study was to investigate the use of FDG PET in patients with suspected liposarcomas (LS). PATIENTS AND METHODS: Forty-two masses were studied. The FDG uptake was estimated in tumor (T) and normal tissue (NT). The data were analyzed with respect to pathological findings. RESULTS: Pathology revealed 11 primary LS, 14 locally recurrent LS, 5 other sarcomas, 1 inflammation, 1 lymphoma and 10 benign lesions. FDG uptake (T-to-NT ratio) in 25 LS corresponded with the histological subtype. Pleomorphic, mixed and myxoid LS showed an increased T-to-NT ratio and were thus visualized. Four out of six well-differentiated LS presented a low FDG uptake. Like subtype, the tumor grade also corresponded to FDG uptake. The T-to-NT ratio of higher grade LS, contrary to low grade LS, was uniformly increased. Primary LS were distinguishable from benign tumors, while other sarcomas, inflammation and lymphoma were not. Recurrence was detected with a sensitivity of 86% and a specificity of 100%. False-negative diagnoses occurred only in well-differentiated recurrences. CONCLUSION: FDG uptake in LS correlates with the histological subtype and tumor grade. The diagnostic value of FDG PET in LS, therefore, is influenced by histomorphological parameters. Our data suggest that pleomorphic, mixed and higher-grade LS recurrences are preferentially amenable to FDG PET imaging.

Modelo de optimización para la selección de plantas en mixturas terapéuticas / Optimization way for the selection of plants in therapeutics mixtures

Se propone una estrategia alternativa para el diseño de productos terapéuticos con mezclas de plantas . Esta estrategia se basa en el método Simplex, un procedimiento empleado para resolver problemas de programación lineal. El método es totalmente compatible con los requerimientos de la OMS y puede ser ampliado y mejorado en su aplicación

Survey and critique of studies related to unlicensed assistive personnel from 1975 to 1997, Part 1.

This descriptive integrated review of research on the use of unlicensed assistive personnel in nursing is presented in two parts. In this issue, part 1 describes the methods used to find and critique research related to unlicensed assistive personnel in nursing. It includes the conceptual model and findings related to the variables studied. Part 2 of this review, which is scheduled for publication in the next issue, will present research findings, conclusions, and recommendations.

Relaciones entre salud pública, seguridad social y funcionalidad del estado / Relationships among public health, social security and the role of the State

Se discute la relación existente entre la salud pública, la seguridad social y la función del estado moderno. Para ello se exploran los antecedentes que le han imprimido identidad a la salud pública como disciplina científica y se postulan hipótesis acerca de lo que ha constituido su objeto de trabajo. Se hace también un recuento de los hechos históricos más significativos en el desarrollo de lo que se ha llamado seguridad social y a partir de algunas hipótesis sobre las regularidades que es posible encontrar en su discurrir histórico, se hacen planteamientos sobre su relación con la salud pública. Se plantea que la prestación de legitimidad del estado está asentada en su funcionalidad como representación del interés colectivo, lo que implica que la garantía de aspectos básicos como la salud, la seguridad social y la vida requieren de la intervención y la regulación estatal. Se concluye que conceptualmente sería absurdo pensar que la salud pública y la seguridad social graviten alrededor de los mecanismos del mercado

Graduate nurse overhires. A cost analysis.

Traditionally, the process for filling vacated nursing positions has contributed to a hiatus between the departure of one nurse and the arrival of another who is prepared to assume patient care responsibility. This is due at least partially to limited work force renewal strategies. Given the cost to temporarily fill vacated positions with agency nurses or to pay nurses overtime rates, current methods of replacing departing nurses may no longer be practical in all cases. The authors discuss the strategy of overhiring graduate nurses and compare these costs to more traditional temporary methods of replacing nurses who have resigned.

Chloride transport activation by plasma osmolarity during rapid adaptation to high salinity of Fundulus heteroclitus.

Transition from low salt water to sea water of the euryhaline fish, Fundulus heteroclitus, involves a rapid signal that induces salt secretion by the gill chloride cells. An increase of 65 mOsm in plasma osmolarity was found during the transition. The isolated, chloride-cell-rich opercular epithelium of sea-water-adapted Fundulus exposed to 50 mOsm mannitol on the basolateral side showed a 100% increase in chloride secretion, which was inhibited by bumetanide 10(-4) M and 10(-4) M DPC (N-Phenylanthranilic acid). No effect of these drugs was found on apical side exposure. A Na+/H+ exchanger, demonstrated by NH4Cl exposure, was inhibited by amiloride and its analogues and stimulated by IBMX, phorbol esters, and epithelial growth factor (EGF). Inhibition of the Na+/H+ exchanger blocks the chloride secretion increase due to basolateral hypertonicity. A Cl-/HCO3- exchanger was also found in the chloride cells, inhibited by 10(-4) M DIDS but not involved in the hyperosmotic response. Ca2+ concentration in the medium was critical for the stimulation of Cl- secretion to occur. Chloride cell volume shrinks in response to hypertonicity of the basolateral side in sea-water-adapted operculi; no effect was found on the apical side. Fresh-water-adapted fish chloride cells show increased water permeability of the apical side. It is concluded that the rapid signal for adaptation to higher salinities is an increased tonicity of the plasma that induces chloride cell shrinkage, increased chloride secretion with activation of the Na+K+2Cl- cotransporter, the Na+/H+ exchanger and opening of Cl- channels.

Autoantibodies against a novel DNA-binding protein: DNA-protein interaction as a requisite for expression of antigenic reactivity.

A novel DNA-binding protein complex, the HB complex, has been characterized by means of autoantibodies. Three proteins of 9000, 7500, and 7000 Da constitute the HB complex. The 9000- and 7500-Da proteins are phosphorylated. Autoantibodies recognize the 7000-Da protein when it is bound to DNA. No reactivity against any protein was observed when the complex was dissociated from DNA. The three proteins are acidic (pI 5-6.2), and the complex was able to bind to synthetic double-stranded DNAs of different composition.

Peripheral blood and bone marrow immunophenotypic and functional modifications induced in acute leukemia patients treated with interleukin 2: evidence of in vivo lymphokine activated killer cell generation.

The effect of treatment with interleukin 2 (IL2) on the phenotypic and functional immune system of acute leukemia patients was investigated. Fifteen acute myeloid leukemia and acute lymphoid leukemia patients with evidence of persistent disease were further subdivided into two groups according to the percentage of bone marrow (BM) blasts: group a had 6-15% blasts and group b had 30-65%. Following two cycles of IL2 (Glaxo Imb, Geneva, Switzerland) given i.v. by continuous infusion at escalating doses, no major changes in the proportion of CD3-, CD4-, and CD8-positive cells were encountered in the blood or in the marrow of either group of patients. When these could be retested after four cycles of IL2, a significant increase of CD3+ and CD4+ cells was documented in the peripheral blood (PB), as well as a significant increase of CD3+ cells in the BM. Irrespective of the number of cycles administered, the proportion of CD16+ cells increased significantly in the blood in both groups of patients and in the marrow of group a patients only. The expression of CD25 was significantly enhanced in all samples tested. Following IL2 administration, an enhancement of the natural killer compartment was documented. This was consistently more evident in patients with more limited disease. A significant amplification of the in vitro-induced lymphokine-activated killer function was noted in the BM of the treated patients. Furthermore, we documented the presence both in the PB and in the BM of "spontaneous" lymphokine-activated killer cells generated in vivo following IL2 administration. These results demonstrate that in acute leukemia of both myeloid and lymphoid origin, treatment with IL2 is capable of inducing profound immunophenotypic and functional modifications in PB and in BM lymphocytes, particularly in patients with more limited disease. The evidence of the in vivo activation of cytotoxic cells, particularly in the BM, may help to explain the clinical responses preliminarily observed in individual acute leukemia patients.

Lymphokine-activated killer (LAK) cell activity in B and T chronic lymphoid leukemia: defective LAK generation and reduced susceptibility of the leukemic cells to allogeneic and autologous LAK effectors.

The capacity to generate lymphokine-activated killer (LAK) cells and the susceptibility of the neoplastic cells to both allogeneic and autologous LAK effectors were studied in B and T chronic lymphoproliferative disorders. While in B-cell chronic lymphocytic leukemia (B-CLL) the depressed natural killer function could be restored after a 7-day incubation with recombinant interleukin (IL-2), B-CLL mononuclear cells showed a reduced LAK activity compared with normal LAK cells. Furthermore, in all but 1 of the 20 B-CLL samples tested the leukemic cells were totally resistant to autologous LAK effectors. In most cases the leukemic cells were also resistant to normal allogeneic LAK cells. Competition experiments demonstrated that the patients' LAK cells, as well as normal LAK effectors, were capable of recognizing B-CLL cells, pointing, therefore, to a postbinding cytolytic defect. In hairy cell leukemia (HCL) an overall reduced LAK activity against allogeneic targets was documented, but, at variance from B-CLL, hairy cells were often susceptible to the lytic effect of normal LAK cells, and in half of the cases tested the neoplastic population was also sensitive in an autologous system. Similarly to B-CLL, in the great majority of T chronic lymphoproliferative disorders studied, the pathologic cells were resistant to normal and autologous LAK effectors and a defective LAK generation was found. These results demonstrate that in most B and T chronic leukemias the LAK function is defective and, when inducible, does not appear directed against the leukemic population. The possibility of exploiting an immunotherapeutic approach with IL-2/LAK cells in the management of chronic lymphoproliferative disorders does not gain support by these findings.

Production of tumor necrosis factor-alpha by B-cell chronic lymphocytic leukemia cells: a possible regulatory role of TNF in the progression of the disease.

Tumor necrosis factor-alpha (TNF) is a cytokine that displays a pleomorphic array of effects on different cell populations. Evidence is presented that TNF may be constitutively produced by B-cell chronic lymphocytic leukemia (B-CLL) and hairy cell leukemia (HCL) cells and that it may play a relevant role in these diseases. These conclusions are based on the presence of circulating levels of TNF in the serum of 20 of the 24 patients tested (83.3%), while undetectable values were found in normal sera. The suggestion that the increased serum levels were due to the leukemic cell population is strengthened by the evidence that purified B-CLL and HCL cells may constitutively release variable degrees of TNF. These levels markedly increase after incubation with interferon gamma or phytohemagglutinin (PHA) plus phorbol myristate acetate (PMA). The cellular release of TNF by primary B-CLL cells was significantly (P less than .001) higher in B-CLL stage O-I patients compared with stage II-III patients. The demonstration that, in B-cell chronic lymphoproliferative disorders, the pathologic cells may release TNF was further confirmed by the presence of the mRNA for this cytokine in primary and/or in pre-activated cells. Recombinant TNF was capable of inducing a proliferative signal only in a minority of cases (4/24); in most cases it was ineffective, and, in a few, it reduced the degree of proliferation. Furthermore, in costimulatory experiments with interleukin-2 and PHA plus PMA, TNF was ineffective. On the other hand, when primary B-CLL cells were incubated in the presence of an anti-TNF antibody, in 8 of 12 independent experiments a 2- to 15-fold increase in thymidine uptake was documented. Taken together, these results suggest that TNF may play a regulatory role in the progression of the neoplastic clone in B-cell chronic lymphoproliferative disorders and may be implicated in some of the side effects associated with these diseases.

Interleukin 2 does not promote the in vitro and in vivo proliferation and growth of human acute leukaemia cells of myeloid and lymphoid origin.

The effect of recombinant interleukin 2 (IL2) on the in vitro and in vivo proliferation and growth of human acute leukaemia cells of both myeloid and lymphoid origin was investigated. In none of the 25 primary samples tested could a continuously in vitro growing cell line be obtained by adding IL2 to the culture medium. Although IL2 induced a proliferative signal in three of the 31 acute leukaemias analysed, the overall 3H-thymidine uptake of the neoplastic cells was significantly reduced (P less than 0.05) in the presence of IL2. The unlikelihood of an important proliferative signal triggered by IL2 was confirmed in a semisolid clonogenic assay, which failed to document an increased colony growth in the 26 samples studied. Furthermore, using a colorimetric assay as a test for cell proliferation and survival, in seven of the 11 fresh acute leukaemia samples tested a 22-40% reduction in viability was observed in the presence of IL2, while in the remaining four, IL2 was ineffective. In order to investigate the effect of IL2 in an in vivo setting, an experimental model in heavily immunosuppressed nu/nu mice was established. In no case did IL2 promote the in vivo proliferation and growth of human myeloid and lymphoid acute leukaemia cells injected in the mice. On the contrary, with seven of the eight leukaemic cell lines which gave rise spontaneously to leukaemic masses, this could be prevented when the mice received locally 300 U of IL2 three times daily for 90 d. IL2 also blocked the growth in vivo of three fresh acute leukaemia samples (two myeloid and one lymphoid). Co-culture experiments using leukaemic cell lines and increasing numbers of normal lymphocytes suggest that the inhibitory effect of IL2 is probably exerted via an indirect mechanism. These findings, coupled to the well-documented ability of IL2 to generate lymphokine activated killer cells cytolytic against leukaemic blasts, further point to the potential role of immunotherapy with IL2 in the management of patients with haematological malignancies.

Lymphokine activated killer (LAK) activity in lymphoproliferative disorders.

Lymphokine activated killer (LAK) cells are being considered as a new and promising form of immunotherapy in the management of patients with solid tumours. Few informations are instead available on these cytotoxic effectors in haematological neoplasias. Here we shall discuss the possible role of LAK cells in human leukaemias. Evidence will be provided for a rationale in the clinical exploitment of Interleukin 2 (IL2)/LAK cells in the treatment of acute leukaemia patients, whilst the implication of these cytotoxic populations appears more uncertain in chronic lymphoproliferative disorders.

[Enflurane-pancuronium combination: real progress toward greater safe conditions in general anesthesia]. / Enflurano-pancuronio: un reale progresso verso sempre maggiori condizioni di sicurezza nell'anestesia generale

The literature data and personal experience with high - and very high - risk patients show that the association of enflurane as anaesthetic and pancuronium as muscle-relaxant constitutes a positive advance in balanced general anaesthesia. Cardiocirculatory depression is not encountered; if anything, there is an improvement of homeostatic conditions. This results in increased safety, even for patients regarded as inoperable. Confirmation of the reasons for associating these two drugs has certainly been obtained. The method cannot, however, be employed indiscriminately, but, at least in theory, should be avoided in patients with serious hypertension or a myocardium that is particularly sensitive to endogenic catecholamine incretion. In hypotension, on the other hand, cases of imminent or frank shock, or situations where surgery cannot be postponed, the association is, paradoxically, a true pharmacological "support", backed up, of course, by other usual procedures. This contradiction of modern views concerning the peripheral circulation is only apparent, since the duration of anaesthesia is reduced; main aim in this period is the maintenance of sufficient circulation to the more important organs. Comparison with associations combining d-Tubocurarine, halothane and methoxyfluorane is still an open question as far as objective assessment of their usefulness is concerned. There can be no doubt, however, that the association of enflurane and pancuronium has eliminated a large sector of contraindications in the field of general anaesthesia.