HDL therapy today: from atherosclerosis, to stent compatibility to heart failure.

Epidemiologically, high-density lipoprotein (HDL) cholesterol levels have been inversely associated to cardiovascular (CV) events, although a Mendelian Randomisation Study had failed to establish a clear causal role. Numerous atheroprotective mechanisms have been attributed to HDL, the main being the ability to promote cholesterol efflux from arterial walls; anti-inflammatory effects related to HDL ligands such as S1P (sphingosine-1-phosphate), resolvins and others have been recently identified. Experimental studies and early clinical investigations have indicated the potential of HDL to slow progression or induce regression of atherosclerosis. More recently, the availability of different HDL formulations, with different phospholipid moieties, has allowed to test other indications for HDL therapy. Positive reports have come from studies on coronary stent biocompatibility, where the use of HDL from different sources reduced arterial cell proliferation and thrombogenicity. The observation that low HDL-C levels may be associated with an enhanced risk of heart failure (HF) has also suggested that HDL therapy may be applied to this condition. HDL infusions or apoA-I gene transfer were able to reverse heart abnormalities, reduce diastolic resistance and improve cardiac metabolism. HDL therapy may be effective not only in atherosclerosis, but also in other conditions, of relevant impact on human health.Key messagesHigh-density lipoproteins have as a major activity that of removing excess cholesterol from tissues (particularly arteries).Knowledge on the activity of high-density lipoproteins on health have however significantly widened.HDL-therapy may help to improve stent biocompatibility and to reduce peripheral arterial resistance in heart failure.

Lógica del capital y salud pública / The logics of capital and public health / A lógica do capital e a saúde pública

Uno de los problemas del sector de la salud es su conceptualización. Se presenta al sector como fragmentado y falto de coordinación. El ciclo del dinero en la circulación del capital permite entender que existe integración de capitales operando bajo la ley de valorización. Las obras sociales aparecen como una forma de pago indirecta que realiza el valor agregado incorporado por los servicios de atención médica. Los hospitales públicos están integrados al capital privado en la fase de compra de los medios de producción, transfi eren valor agregado como subsidios implícitos al dar atención a la población que tiene cobertura y confi guran un ciclo trunco del dinero que impide su recuperación provocando deterioro y subutilización del capital público. En el trabajo se buscan levantar dudas sobre la perspectiva de la fragmentación que es la que plantea falta de articulación entre sub-sectores. Los autores argumentan una integración entre salud pública y privada en condiciones de subordinación de lo público a la lógica de valoración del capital. No se plantea dicotomía, sino integración orientada a la realización del valor agregado de las empresas constructoras y fármaco-químicas, entre otros.

One of the problems of the health area is its conceptualization. The sector is presented as fragmented and lacking coordination. The money cycle in the circulation of capital lets us understand that there is integration of capitals taking place under the valorization law. Health care schemes appear as an indirect method of payment making the added value incorporated by health care services. Public hospitals are integrated to private capital in the stage of buying production means, they transfer added value as implicit subsidies when seeing patients with medical insurance and form and incomplete cycle of money which hinders recovery causing deterioration and under-usage of public capital. In this work we try to create doubts about the perspective of fragmentation which sets out the lack of articulation among the sub-sectors. The authors state there is integration between public and private health in conditions of subordination of the public to the logic of the valuation of capital. They do not set out a dichotomy, but integration oriented towards the achievement of added value of building, drug and chemical companies among others.

Um dos problemas do sector da saúde é a sua conceituação. Ele apresenta-se como fragmentado e descoordenado. O ciclo do dinheiro na circulação do capital permite-nos compreender que existe uma integração entre o capital operando sob a lei de valorização. Os Planos de Saúde aparecem como uma forma de pagamento indireto feito pelo valor acrescentado incorporado por serviços de saúde. Os hospitais públicos são integrados ao capital privado no processo de compra de meios de produção, transferem valor acrescentado como subsídios implícitos ao dar cuidados médicos à população que tem esta cobertura e defi nem um ciclo truncado de dinheiro que impede a sua recuperação causando deterioração e subutilização do capital público. Neste trabalho procura-se gerar dúvidas sobre a perspectiva de fragmentação que é representada pela falta de coordenação entre os subsectores. Os autores argumentam uma integração entre a saúde pública e a privativa em condições de subordinação do público à lógica de valorização do capital. Dicotomias não são apresentadas mas uma integração visando a realização do valor acrescentado das empresas da construção e fármaco químicas entre outras.

Beta2-adrenergic activity modulates vascular tone regulation in lecithin:cholesterol acyltransferase knockout mice.

Lecithin:cholesterol acyltransferase (LCAT) deficiency is associated with hypoalphalipoproteinemia, generally a predisposing factor for premature coronary heart disease. The evidence of accelerated atherosclerosis in LCAT-deficient subjects is however controversial. In this study, the effect of LCAT deficiency on vascular tone and endothelial function was investigated in LCAT knockout mice, which reproduce the human lipoprotein phenotype. Aortas from wild-type (Lcat(wt)) and LCAT knockout (Lcat(KO)) mice exposed to noradrenaline showed reduced contractility in Lcat(KO) mice (P<0.005), whereas acetylcholine exposure showed a lower NO-dependent relaxation in Lcat(KO) mice (P<0.05). Quantitative PCR and Western blotting analyses suggested an adequate eNOS expression in Lcat(KO) mouse aortas. Real-time PCR analysis indicated increased expression of ß2-adrenergic receptors vs wild-type mice. Aorta stimulation with noradrenaline in the presence of propranolol, to abolish the ß-mediated relaxation, showed the same contractile response in the two mouse lines. Furthermore, propranolol pretreatment of mouse aortas exposed to L-NAME prevented the difference in responses between Lcat(wt) and Lcat(KO) mice. The results indicate that LCAT deficiency leads to increased ß2-adrenergic relaxation and to a consequently decreased NO-mediated vasodilation that can be reversed to guarantee a correct vascular tone. The present study suggests that LCAT deficiency is not associated with an impaired vascular reactivity.

Desarrollo, medio ambiente y salud / Development, environment and health / Desenvolvimento, meio ambiente e saúde

Las fuerzas productivas y las relaciones de produccióncapitalistas se han expandido a nivel mundial. Esto semanifiesta en la acumulación de capital e industrializaciónen Asia y Latinoamérica, lo cual, conlleva un proceso deurbanización, caída de la población rural y proletarizaciónde la fuerza laboral. Esta acumulación de capital, haproducido una acumulación de dióxido de carbono quesupera el mínimo tolerable para la sustentabilidad de lavida. También influye sobre la distribución de la riqueza,cuya desigualdad permanece estable en las últimas décadas.Los efectos del daño ambiental y la desigualdad impactansobre la salud poblacional. Este trabajo, indaga por un lado,sobre la dicotomía riqueza y desarrollo, que refleja el gradode inequidad en las sociedades contemporáneas y analizalos efectos de la contaminación del aire y el agua sobre lasalud humana.

Productive forces and capitalist production relationships have expanded worldly. This isseen in the accumulation of capital and industrialization in Asia and Latin America, whichinvolves a process of urbanization, a fall of rural population and proletarianization of thework force. This accumulation of capital has produced an accumulation of carbon dioxideexceeding the bearable minimum for life sustainability. It also has an influence on wealthdistribution; inequality which has remained stable over the last decades. The effects of thisenvironmental damage and inequality have an impact on the population´s health. Thiswork investigates about the dichotomy wealth - development which reflects the degree ofinequality in contemporary societies and, on the other side, analyzes the effects of air andwater pollution on human health.

Capitalismo, Medio Ambiente, Desigualdad y Salud / Capitalism, environment, inequality and health / Capitalismo, meio ambiente, desigualdade e saúde

El presente trabajo plantea que más allá de las crisis cíclicas del capitalismo, existe una crisis del sistema en sí, ya que la lógica de crear mayor riqueza ha sobrepasado las condiciones de tolerancia de la capacidad reproductiva del medio ambiente, a límites ya no permitidos para el bienestar humano. Por otro lado, este sistema económico que determina las relaciones entre los factores de la producción, arreglado a la maximización de ganancias y minimización de costos, no soluciona las inequidades en el mundo, respecto a la distribución de la riqueza. En efecto el 80% de la población más pobre no alcanza a la distribución del 20% de la renta y el 0,2% más rico se adjudica el 20% de la misma. Los resultados también indican que la inequidad genera mayor mortalidad infantil y mortalidad por enfermedades transmisibles

This work states that beyond the cyclic crisis of capitalism, the system itself is in crisis, since the logic of creating greater wealth has exceeded the conditions of tolerance of the reproductive capacity of the environment, to limits not permitted for human welfare. On the other hand, this economic system that determines the relationships among production factors, settling the maximization of earnings and the minimization of costs, does not solve the world’s inequalities as regards wealth distribution. In fact, 80% of the poorest population does not reach the 20% distribution of incomes and the richest 0.02% keep 20% of it. Results also show that inequality also generates greater child mortality and mortality due to communicable diseases

Factores de riesgo y determinantes de la salud / Risk and determinig health factors

Este trabajo examina, el grado de relación existente entre indicadores de riesgo y sociodemográficos de los distritos políticos de Argentina y su variabilidad entre 2005 y 2009. Alcance descriptivo y correlacional. Diseño retrospectivo longitudinal. Se encontraron correlaciones múltiples entre indicadores de cobertura, controles médicos, urbanización, PGB y hábitos no saludables como consumo de riesgo de sal, tabaco y alcohol. Por otro lado una población con NBI, analfabetismo y autopercepción de salud regular/mala, aún con establecimientos públicos de salud sin internación. Argentina presenta tres tipologías de provincias, las centrales y patagónicas, con buena cobertura y hábitos no saludables, las norteñas con alta vulnerabilidad social y un grupo intermedio. Entre 2005 y 2009, si bien aumentó la cobertura de salud, y los controles de la misma, disminuyendo la autopercepción de salud/regular mala, no se evidencian mejoras en los parámetros fisiológicos poblacionales, aumentó la inactividad física, el consumo de sal y la obesidad

This work examines the extent of existing relationship between risk and socio-demographic indicators in the different political districts in Argentna and its variability from 2005 to 2009. Descriptive and correlational research with retrospective longitudinal design. Multiple correlations were found among indicators of coverage, medical controls, urbanization, GGP and unhealthy habits such as risky consumption of salt, tobacco and alcohol. On one side, a population with unsatisfied basic needs (UBN), illiteracy and health self-perception as regular/poor, still with public health facilities without possible hospitalization. Argentina presents three province typologies: the central and Patagonian provinces with good coverage and unhealthy habits; the northern ones with high social vulnerability and an intermediate group. Although health coverage and controls increased and health self-perception as regular/poor decreased, between 2005 and 2009 we did not observe improvements in population physiological parameters; besides, physical inactivity, salt consumption and obesity increased

The impact of the Val158Met catechol-O-methyltransferase genotype on neural correlates of sad facial affect processing in patients with bipolar disorder and their relatives.

BACKGROUND: The Met allele of the catechol-O-methyltransferase (COMT) valine-to-methionine (Val158Met) polymorphism is known to affect dopamine-dependent affective regulation within amygdala-prefrontal cortical (PFC) networks. It is also thought to increase the risk of a number of disorders characterized by affective morbidity including bipolar disorder (BD), major depressive disorder (MDD) and anxiety disorders. The disease risk conferred is small, suggesting that this polymorphism represents a modifier locus. Therefore our aim was to investigate how the COMT Val158Met may contribute to phenotypic variation in clinical diagnosis using sad facial affect processing as a probe for its neural action. METHOD: We employed functional magnetic resonance imaging to measure activation in the amygdala, ventromedial PFC (vmPFC) and ventrolateral PFC (vlPFC) during sad facial affect processing in family members with BD (n=40), MDD and anxiety disorders (n=22) or no psychiatric diagnosis (n=25) and 50 healthy controls. RESULTS: Irrespective of clinical phenotype, the Val158 allele was associated with greater amygdala activation and the Met158 allele with greater signal change in the vmPFC and vlPFC. Signal changes in the amygdala and vmPFC were not associated with disease expression. However, in the right vlPFC the Met158 allele was associated with greater activation in all family members with affective morbidity compared with relatives without a psychiatric diagnosis and healthy controls. CONCLUSIONS: Our results suggest that the COMT Val158Met polymorphism has a pleiotropic effect within the neural networks subserving emotional processing. Furthermore the Met158 allele further reduces cortical efficiency in the vlPFC in individuals with affective morbidity.

Educación y salud como input del capital humano: rendimento académico de estudiantes de la facultad de ciências económicsa: UNRC / Health and education as human capital input, academic performance of economic sciences students: national university of Rio Cuarto

Este trabajo busca establecer asociaciones entre atributossociodemográficos de alumnos universitarios con su rendimiento académico. El alcance del estudio es descriptivo y correlacional y el diseño retrospectivo, transversal. Los resultados sugieren que la regularización de asignaturaspor parte del alumno, la eficiencia académica (asignaturas aprobadas / asignaturas rendidas), el nivel educativo del padre y de la madre, son colineales entre sí. En un planofactorial muy cercano se presentan la gestión de la escuela secundaria (privada), no habiendo tanta cercanía con el plan de estudios, mientras que juegan en contra del buen rendimiento del alumno la edad del ingresante (mayor de 18años), la presencia de pareja o hijos y si trabaja.

The aim of this study is to establish associations between sociodemographic attributes and academic performance. This is a descriptive correlational study with retrospective transversal design. Results suggest that taking subjects,academic efficiency (passed subjects/subjects sat for) andeducational level of mother and father appear on the same line. In a factorial plane we find high school administration (private) very close, the syllabus a little further and against the student’s good performance we find age of entrance (over 18), presence of couple or children and job.

Effects of chronic treatment with statins and fenofibrate on rat skeletal muscle: a biochemical, histological and electrophysiological study.

BACKGROUND AND PURPOSE: Skeletal muscle injury by hypolipidemic drugs is not fully understood. An extensive analysis of the effect of chronic treatment with fluvastatin (5 mgkg(-1) and 20 mgkg(-1)), atorvastatin (10 mgkg(-1)) and fenofibrate (60 mgkg(-1)) on rat skeletal muscle was undertaken. EXPERIMENTAL APPROACH: Myoglobinemia as sign of muscle damage was measured by enzymatic assay. Histological and immunohistochemical techniques were used to estimate muscle integrity and the presence of aquaporin-4, a protein controlling water homeostasis. Electrophysiological evaluation of muscle Cl(-) conductance (gCl) and mechanical threshold (MT) for contraction, index of intracellular calcium homeostasis, was performed by the two-intracellular microelectrodes technique. KEY RESULTS: Fluvastatin (20 mgkg(-1)) increased myoglobinemia. The lower dose of fluvastatin did not modify myoglobinemia, but reduced urinary electrolytes, suggesting direct effects on renal function. Atorvastatin also increased myoglobinemia, with slight effects on urinary parameters. No treatment caused any histological damage to muscle or modification in the number of fibres expressing aquaporin-4. Either fluvastatin (at both doses) or atorvastatin reduced sarcolemma gCl and changed MT. Both statins produced slight effects on total cholesterol, suggesting that the observed modifications occur independently of HMGCoA-reductase inhibition. Fenofibrate increased myoglobinemia and decreased muscle gCl, whereas it did not change the MT, suggesting a different mechanism of action from the statins. CONCLUSIONS AND IMPLICATIONS: This study identifies muscle gCl and MT as early targets of drugs action that may contribute to milder symptoms of myotoxicity, such as muscle cramps, while the increase of myoglobinemia is a later phenomenon.

Occurrence of Sclerotinia Stem Rot of Osteospermum sp., Felicia amelloides, and Ranunculus asiaticus in Argentina.

Three ornamental species, Osteospermum sp. (L.), Felicia amelloides (L.) Voss, and Ranunculus asiaticus L., cultivated in greenhouses on the outskirts of Buenos Aires, showed sudden wilt and death during October 2002. These species are new ornamentals in Argentina. The diseased plants were cultivated in plastic containers filled with commercial potting mix. Soft rot was observed at the base of the plants. Stem lesions became covered with whitish mycelium that produced large, black sclerotia (5 to 7 mm in diameter) characteristic of Sclerotinia sclerotiorum (Lib.) de Bary (1). The fungus was consistently recovered from infected stem pieces that were disinfested for 1 min in 0.2% NaOCl and plated on potato dextrose agar (PDA), pH 7. Pathogenicity of the three isolates obtained from infected plants was confirmed by inoculating 10 3-month-old healthy plants of each species in 14-cm-diameter plastic pots. Each isolate was inoculated on the host from which it had been isolated. Inoculum consisted of three mycelial plugs from 7-day-old PDA cultures that were placed on the substrate at the base of the plants. Control plants were treated with sterile agar plugs. Inoculated and noninoculated plants were covered with transparent plastic bags for 2 days and incubated in a growth chamber at 20 to 24°C with a 12-h photoperiod. All inoculated plants developed symptoms of leaf yellowing and wilt. Soft and watery tissues were observed at the base of the plants, soon followed by the appearance of white mycelium. Disease symptoms were similar to those observed on the original infected plants and appeared 6, 5, and 3 days after inoculation on Osteospermum sp., F. amelloides, and R. asiaticus, respectively. All inoculated plants died within 3 weeks, and control plants remained healthy. S. sclerotiorum was reisolated from inoculated plants of each species, fulfilling Koch's postulates. To our knowledge, this is the first report of the occurrence of Sclerotinia stem rot on these three plant species in Argentina. Reference: (1) J. E. M. Mordue and P. Holliday. No. 513 in: Descriptions of Pathogenic Fungi and Bacteria. CMI, Kew, Surrey, UK. 1976.

Evaluation of a soft atherosclerotic lesion in the rabbit aorta by an invasive IVUS method versus a non-invasive MRI technology.

The intravascular ultrasound (IVUS) modality has rapidly gained acceptance for the measurement of arterial plaque thickness and for anatomical characterization. In view, however, of the growing interest in the direct assessment of plaque size after therapeutic modalities directly reducing plaque burden, a non-invasive method such as magnetic resonance imaging (MRI) may be of help for repeated evaluations. The two methods were compared directly on a focal plaque developed at the abdominal aortic level by a combination of local electric lesion followed by a hypercholesterolemic diet. The plaque was fully characterized histopathologically at intervals up to 120 days from lesion induction, and maximal plaque formation was detected at 90 days from electrical injury. Plaques could be well assessed by IVUS at each time point analyzed and data correlated very well to histopathologic findings (r = 0.969, P = 0.0014). The MRI technology provided reliable determinations only at 90 days after lesion induction, i.e. at maximal plaque formation, with excellent correspondence to IVUS determinations (r = 0.989, P = 0.0111). Altogether these findings indicate that the non-invasive MRI technology, when applied to the analysis of arterial plaques of adequate size, can be used successfully for plaque determination, with results comparable to the invasive IVUS technique.

Development of a lipid-rich, soft plaque in rabbits, monitored by histology and intravascular ultrasound.

Lipid rich, soft plaques in the clinic are a common forerunner to occlusive thrombus formation, even with modest arterial stenosis. Animal models of atherosclerosis, obtained by various methods, do not generally allow direct in vivo evaluation of the lesion and, furthermore, cannot be examined more than once. The aim of the study was the generation of a rabbit model of atherosclerosis, with morphological characteristics similar to human lipid-rich, soft atheromatous plaques, and the evaluation of the reliability of intravascular ultrasound (IVUS) technology in the study of the development of atherosclerotic lesions in this model. Briefly, New Zealand white rabbits undergo perivascular electrical injury at both common carotid arteries, together with a 1.5% cholesterol diet for up to 90 days. The lesioned arterial segments show progressive changes, from diffuse cellular mortality, to macrophage infiltration in the media, up to the final migration of macrophages to the neointima, resulting in bulky, eccentric, macrophage and lipid-rich lesions. At IVUS, the produced lesions clearly resemble those described as 'soft plaques' in the clinical setting, with minimal calcification and reduced echo-reflectivity versus the adventitial layer. Quantitative and morphometric analysis of plaques shows a significant correlation between histological and IVUS measurements at each time point. In conclusion, vascular injury in the common carotids of rabbits generates atherosclerotic lipid-rich, soft plaques, that can be properly assessed by the IVUS methodology. The easy accessibility of the arterial lesion allows serial IVUS investigations and the direct evaluation of a number of locally or generally delivered therapeutic agents.

Leukotriene D4-induced activation of smooth-muscle cells from human bronchi is partly Ca2+-independent.

Cysteine-containing leukotrienes (cysteinyl-LTs) are potent bronchoconstrictors and play a key role in asthma. We found that histamine and LTD4 markedly constrict strips of human bronchi (HB) with similar efficacy. However, in human airway smooth-muscle (HASM) cells, LTD4, at variance with histamine, elicited only a small, transient change in intracellular calcium ion concentration. HASM cells express both Ca2+-dependent and -independent isoforms of protein kinase C (PKC) (i.e., PKC-alpha and PKC-alpha ). Western blot analysis showed that PKC-alpha is activated by histamine and, to a lesser extent, by LTD4, whereas only LTD4 translocates PKC-alpha. This translocation was specifically inhibited by the LTD4 antagonist pobilukast. Phorbol-dibutyrate ester (PDBu) (a PKC activator) contracted HB strips to the same extent in the presence as in the absence of extra- and intracellular Ca2+. In the absence of Ca2+, LTD4 contracted HB strips to the same extent as did PDBu, suggesting the involvement of a Ca2+-independent PKC in LTD4-mediated signal transduction. PDBu-induced desensitization and the PKC inhibitor H7 abolished the slow and sustained LTD4-triggered contraction of HB strips in the absence of Ca2+, although H7 did not greatly affect the response in the presence of the ion. Thus, in human airways, we identified a novel LTD4 transduction mechanism linked to bronchial smooth-muscle contraction, which is partly independent of Ca2+ and involves the activation of PKC-alpha.

Effect of endogenous and exogenous prostaglandin E(2) on interleukin-1 beta-induced cyclooxygenase-2 expression in human airway smooth-muscle cells.

We studied the effect of endogenous and exogenous prostaglandin E(2) (PGE(2)), a metabolite of arachidonic acid through the cyclooxygenase (COX) pathway, on interleukin (IL)-1 beta-induced COX-2 expression, using primary cultures of human bronchial smooth-muscle cells (HBSMC). Treatment with exogenous PGE(2) resulted in enhanced expression of IL-1 beta-induced COX-2 protein and messenger RNA (mRNA) as compared with the effect of the cytokine per se. Inhibition of PGE(2) production with a nonselective COX inhibitor (flurbiprofen, 10 microM) resulted in a significant reduction in IL-1 beta- induced COX-2 expression, supporting a role of endogenous COX metabolites in the modulation of COX-2 expression. None of the experimental conditions used in the study affected the expression of constitutive cyclooxygenase (COX-1). Treatment with cycloheximide to inhibit translation, and with dexamethasone or actinomycin D to inhibit transcription, linked the effect of PGE(2) to the transcriptional level of COX-2 mRNA rather than to a potential effect on protein and/or mRNA stabilization. PGE(2) increased adenylate cyclase activity in a concentration dependent manner, and forskolin, a direct activator of adenylate cyclase, caused a marked increase in IL-1 beta-dependent COX-2, suggesting the existence of a causal relationship between the two events. The same results were observed with salbutamol, a bronchodilator that acts by increasing cyclic adenosine monophosphate. The effect of PGE(2) on COX-2 expression may contribute to the hypothesized antiinflammatory role of PGE(2) in human airways, providing a self-amplifying loop leading to increased biosynthesis of PGE(2) during an inflammatory event.

Liposome-delivered angiostatin strongly inhibits tumor growth and metastatization in a transgenic model of spontaneous breast cancer.

The possibility to inhibit tumor growth by interfering with the formation of new vessels, which most neoplasias depend on, has recently raised considerable interest. An angiogenic switch, in which proliferating cells acquire the ability to direct new vessel formation, is thought to be an early step in the natural history of solid tumors. Using a transgenic model of breast cancer, which shows many similarities to its human counterpart, including ability to metastasize, we targeted angiostatin production to an early stage of tumor formation. Liposome-delivered angiostatin considerably delayed primary tumor growth and, more importantly, inhibited the appearance of lung metastases. These findings can be relevant to the design of therapeutic intervention in humans.

[Percutaneous or surgical trachetomy. Prospective, randomized comparison of the incidence of early and late complications]. / Tracheotomia percutanea e chirurgica. Confronto prospettico, randomizzato dell'incidenza di complicanze precoci e tardive.

BACKGROUND: To compare early and late complications after either conventional surgical or percutaneous dilatational tracheostomy. DESIGN: Prospective, randomized study. SETTING: General intensive care unit and neuro-surgical intensive care unit in a university hospital. PATIENTS: 50 consecutive patients, requiring tracheostomy for prolonged mechanical ventilation. INTERVENTIONS AND MEASUREMENTS: Patients were randomly allocated to receive either surgical (surgical group, n = 25) or percutaneous dilatational tracheostomy (percutaneous group, n = 25). Occurrence of perioperative complication were carefully evaluated during ICU stay. Late complications were evaluated with both physical and endoscopic examination at 1, 3 to 6 months after tracheostomy. RESULTS: All surgical and percutaneous tracheostomies were successfully completed and no deaths directly related to the tracheostomy procedures were reported. Completion of the procedure required 41 +/- 14 min in the surgical group and 14 +/- 6 min in the percutaneous one (p < 0.0001). The incidence of early perioperative complications was higher in the surgical group (36%) than in percutaneous one (12%), (p < 0.05). The endoscopic follow-up demonstrated one segmental malacia and one stenosis of the trachea in the percutaneous group only (p = n.s.). Skin repair was better after percutaneous tracheostomy than in the surgical group (p < 0.01). CONCLUSIONS: In experienced hands, percutaneous dilatational tracheostomy is as safe and effective as the conventional surgical tracheostomy. The percutaneous technique is less time-consuming and has a lower rate of early infectious complications with better cosmetic results than the surgical technique.

Improvement of pulmonary function after lobectomy for non-small cell lung cancer in emphysematous patients.

OBJECTIVE: Pulmonary emphysema is frequently associated with lung cancer and, because of the impaired pulmonary function involved, it may contraindicate surgical treatment. However, improvement of pulmonary function has been observed after surgical resection in patients with advanced emphysema. The aim of this study was to evaluate whether pulmonary emphysema, as assessed by pulmonary function tests and radiological evaluation, can influence postoperative respiratory function after lobectomy for non-small cell lung cancer (NSCLC). METHODS: Respiratory function was evaluated before and after lobectomy for NSCLC. Radiological evaluation of emphysema was performed on chest X-ray and CT scan. Patients that had undergone chemo- or radiotherapy or had segmental or lobar atelectasis were excluded from the study. RESULTS: Thirty-five patients entered the study. A decrease in static lung volumes was observed after surgery. Total lung capacity (TLC) decreased from 6.58+/-0.92 to 5.46+/-0.77 l; functional residual capacity (FRC) from 3.70+/-0.88 to 2.96+/-0.73 1 and residual volume (RV) from 2.93+/-0.78 to 2.2+/-0.53 l. However, in a subgroup of 10 patients (Group 1), dynamic volumes after surgery were unchanged or slightly increased (forced vital capacity (FVC) from 3.23+/-0.65 to 3.3+/-0.68 l; forced expiratory volume in 1 s (FEV1) from 2.14+/-0.51 to 2.25+/-0.54 l), and airway resistances (sRaw) decreased from 15.58+/-5.18 to 11.42+/-5.25 cm H2O/s. Preoperative data showed that these patients had a greater obstruction, with FEV1 changing from 69+/-12.42 to 72.70+/-13.72% of predicted, as compared with a change from 87+/-12.7 to 72.08+/-13.10% in the other group of 25 patients (Group 2). Correlation analysis reached statistical significance between FEV1% variation (deltaFEV1%) and preoperative FEV1 and FVC% (r = -0.49, P = 0.002 and r = -0.5, P = 0.001, respectively) and between delta (FEV1)% and radiological scores for 3-level CT (r = 0.39, P = 0.04) and the sum of chest X-ray, single and 3-level CT scores (r = 0.49, P = 0.01). CONCLUSIONS: Pulmonary function may remain unchanged or even increase after lobectomy in patients with a pronounced emphysematous component of airway obstruction. The identification of preoperative parameters that identify this group of patients could extend the indications for the treatment of lung cancer in patients with pulmonary emphysema.

Transgenic mice expressing a human apolipoprotein[a] allele.

The most important determinant of plasma levels of Lp[a] are sequence differences at the highly polymorphic apolipoprotein[a] (apo[a]) locus. To define the sequences that mediate the regulation of apo[a] expression, we cloned a 370 kb DNA fragment that included a 130 kb apo[a] gene, and 40 kb 5'- and 200 kb 3'-flanking region from an individual with high plasma levels of Lp[a] using a YAC vector. This genomic clone was used to generate transgenic mice. In the YAC-apo[a] transgenic mouse, apo[a] was only expressed in the liver, as it is in humans. The mean serum level of apo[a] in 4-week-old YAC-apo[a] transgenic mice was 20 mg/dl. In the female mice the levels of apo[a] varied over a 1.5-fold range during the 4-day estrus cycle and the levels correlated directly with serum progesterone levels. The serum levels of apo[a] decreased to almost undetectable level in male mice after puberty and this decrease was reversed by castration. Ingestion of a high-fat diet resulted in a approximately 100-fold fall in hepatic apo[a] mRNA levels and >60-fold decrease in serum apo[a] levels. To delimit the control elements that mediate tissue-specific and sex hormone-responsive apo[a] transcription, we derived a reporter YAC in which 40 kb of 5' flanking sequences from the cloned apo[a] allele were linked to a luciferase reporter gene. Analysis of four independent transgenic lines revealed no hepatic luciferase expression, suggesting that important cis -acting elements located outside the apo[a] 5'-flanking region are necessary for in vivo expression of apo[a].