Towards a standardized initial training program in experimental microsurgery for pediatric surgeons. / Hacia un programa inicial de formación estandarizadoen microcirugía experimental para cirujanos pediátricos.

OBJECTIVE: To describe a basic training program in microsurgery and to analyze the learning curve through the process, including improvement in operating times and functional outcome. MATERIALS AND METHODS: Our learning program included basic, transitional, and experimental models. The experimental model included tail vein cannulation, intestinal resection and anastomosis, dissection, division and anastomosis of the cava and aorta. Wistar rats (66.7% male; 406.9 ± 38.9 grams) were used. The program adhered to the 3R principle and obtained animal welfare committee approval. RESULTS: Mean tail vein cannulation time was 2.4 ± 1.2 minutes. Mean intestinal resection and jejunocolic anastomosis time was 14.8 ± 2.7 minutes and 10.4 ± 3 minutes, respectively. All anastomoses were functionally valid. Mean vessel dissection time was 22.9 ± 7.7 minutes, aortic artery anastomosis was 17.2 ± 7.1 minutes, and vena cava anastomosis was 25.9 ± 7.3 minutes. 66.7% of vena cava anastomoses were functionally valid vs. 88.9% for the aorta. The time required for all procedures decreased after the third attempt, except for vena cava anastomoses, which remained similar in all 9 procedures. CONCLUSIONS: Our model demonstrated that the procedures were suitable for trainer progression in terms of surgical time and functional outcome. Microsurgical training would benefit from standardized programs to optimize results.

OBJETIVO: Describimos un programa de formación básica en microcirugía y analizamos la curva de aprendizaje a través del proceso, incluyendo la mejora en los tiempos operatorios y en el resultado funcional del procedimiento. MATERIAL Y METODOS: Nuestro programa de aprendizaje incluye modelos básicos, de transición y experimentales. Dentro del modelo experimental se incluyeron: canulación de la vena de la cola, resección y anastomosis intestinal, disección, sección y anastomosis de la cava y la aorta. Se emplearon ratas Wistar (66,7% machos; 406,9 ± 38,9 gramos), el programa se adhirió al principio de las 3R y obtuvo la aprobación del comité de bienestar animal. RESULTADOS: El tiempo medio de canulación de la vena de la cola fue de 2.4 ± 1,2 minutos. El tiempo medio de resección intestinal y anastomosis yeyunocólica de 14.8 ± 2,7 minutos y 10.4 ± 3 minutos, respectivamente. Todas las anastomosis fueron funcionalmente válidas. El tiempo medio de la disección de vasos fue de 22,9 ± 7,7 minutos, la anastomosis de la arteria aorta de 17,2 ± 7,1 minutos, mientras que la anastomosis de la vena cava fue de 25,9 ± 7,3 minutos. El 66,7% de las anastomosis de la vena cava fueron funcionalmente válidas en comparación con el 88,9% de la aorta. El tiempo requerido para todos los procedimientos disminuyó después del tercer intento, excepto para las anastomosis de vena cava, que se mantuvo similar en los 9 procedimientos. CONCLUSIONES: Nuestro modelo demostró que los procedimientos eran adecuados para la progresión del entrenador en términos de tiempo quirúrgico y resultado funcional. La formación microquirúrgica se beneficiaría de programas estandarizados para optimizar los resultados.

[Pre-clinical validation of a turbine-based ventilator for invasive ventilation-The ACUTE-19 ventilator]. / Validación preclínica de un respirador de turbina para la ventilación invasiva: el respirador ACUTE-19.

Background: The severe acute respiratory syndrome-coronavirus 2 pandemic pressure on healthcare systems can exhaust ventilator resources, especially where resources are restricted. Our objective was a rapid preclinical evaluation of a newly developed turbine-based ventilator, named the ACUTE-19, for invasive ventilation. Methods: Validation consisted of (a) testing tidal volume delivery in 11 simulated models, with various resistances and compliances; (b) comparison with a commercial ventilator (VIVO-50) adapting the United Kingdom Medicines and Healthcare products Regulatory Agency-recommendations for rapidly manufactured ventilators; and (c) in vivo testing in a sheep before and after inducing acute respiratory distress syndrome by saline lavage. Results: Differences in tidal volume in the simulated models were marginally different (largest difference 33 ml [95% CI 31 to 36]; P < .001). Plateau pressure was not different (-0.3 cmH2O [95% CI -0.9 to 0.3]; P = .409), and positive end-expiratory pressure was marginally different (0.3 cmH2O [95% CI 0.2 to 0.3]; P < .001) between the ACUTE-19 and the commercial ventilator. Bland-Altman analyses showed good agreement (mean bias -0.29 [limits of agreement 0.82 to -1.42], and mean bias 0.56 [limits of agreement 1.94 to -0.81], at a plateau pressure of 15 and 30 cmH2O, respectively). The ACUTE-19 achieved optimal oxygenation and ventilation before and after acute respiratory distress syndrome induction. Conclusions: The ACUTE-19 performed accurately in simulated and animal models yielding a comparable performance with a VIVO-50 commercial device. The ACUTE-19 can provide the basis for the development of a future affordable commercial ventilator.

Initial clinical outcomes and prognostic variables in the implementation of a Code Sepsis in a high complexity University Hospital.

OBJECTIVE: To assess the impact of the first months of application of a Code Sepsis in a high complexity hospital, analyzing patient´s epidemiological and clinical characteristics and prognostic factors. METHODS: A long-term observational study was carried out throughout a consecutive period of seven months (February 2015 - September 2015). The relationship with mortality of risk factors, and analytic values was analyzed using uni- and multivariate analyses. RESULTS: A total of 237 patients were included. The in-hospital mortality was 24% at 30 days and 27% at 60 days. The mortality of patients admitted to Critical Care Units was 30%. Significant differences were found between the patients who died and those who survived in mean levels of creatinine (2.30 vs 1.46 mg/dL, p <0.05), lactic acid (6.10 vs 2.62 mmol/L, p <0.05) and procalcitonin (23.27 vs 12.73 mg/dL, p<0.05). A statistically significant linear trend was found between SOFA scale rating and mortality (p<0.05). In the multivariate analysis additional independent risk factors associated with death were identified: age > 65 years (OR 5.33, p <0.05), lactic acid > 3 mmol/L (OR 5,85, p <0,05), creatinine > 1,2 mgr /dL (OR 4,54, p <0,05) and shock (OR 6,57, P <0,05). CONCLUSIONS: The epidemiological, clinical and mortality characteristics of the patients in our series are similar to the best published in the literature. The study has identified several markers that could be useful at a local level to estimate risk of death in septic patients. Studies like this one are necessary to make improvements in the Code Sepsis programs.

Photosynthetically active radiation and carbon gain drives the southern orientation of Myrtillocactus geometrizans fruits.

The equatorial orientation of reproductive structures is known in some columnar cacti from extratropical deserts. It has been hypothesised that photosynthetically active radiation (PAR) interception is the main reason for this orientation, because of its key effect on nocturnal CO2 uptake. However, there are no studies addressing both the effect of PAR and its consequence, carbon gain, on fruit orientation. Accordingly, we tested whether PAR and carbon gain could explain the southern fruit orientation of Myrtillocactus geometrizans, an inter-tropical columnar cactus. We studied three populations of M. geometrizans in Mexico. For each population, azimuth of fruits, total daily PAR, nocturnal acid accumulation (NAA) and fruit production were measured. The relationships between rib orientation and number of fruits, as well as total daily PAR, were evaluated using periodic regressions. The effect of total daily PAR and NAA on number of fruits was assessed using generalised linear models. During spring, mean fruit orientation had a south azimuth for three populations. Likewise, rib orientation had a significant effect on fruit production, with the south-facing ribs having the maximum number of fruits. Total daily PAR was highest in the south-facing ribs, at least for those in the northern and central populations. Furthermore, during spring, there was a significant positive effect of total daily PAR and NAA on fruit production. Our results provide strong evidence that the higher carbon gain in equatorial ribs, through a highest interception of PAR, would be the responsible factor for equatorial orientation of fruits in an inter-tropical columnar cactus.

Abdominal cystic lymphangiomas in pediatrics: surgical approach and outcomes.

BACKGROUND: Abdominal Cystic lymphangiomas (ACL) are uncommon benign masses usually presented during infancy. Although extremely rare, they may cause complications; therefore, the recommended therapy is surgical excision. The purpose of this study is to report our experience with the diagnosis and surgical treatment of ACL in pediatric population. MATERIAL AND METHODS: From January 1994 to December 2009, 10 patients (6 females; 4 males) with diagnostic confirmation of ACL were retrospectively included in study. Children's age ranged between 9 months and 8 years (mean age at diagnosis was 2.5 years). Clinical presentation, cyst location, imaging studies employed, surgical approach and pathologic features were analyzed. RESULTS: The most common symptom was abdominal pain but three cases were incidentally detected. One case had presented with acute abdomen after traumatic haemorrhage of the tumor. All patients were diagnosed with ultrasonography as first-line radiological study. MRI was used in last three cases. At surgery, concomitant bowel resection was necessary in 3 children. Location of the lesion (omentum, mesentery) did not influence the outcome but surgery was more difficult (operative time over three hours) in patients with lymphangioma affecting mesentery of the jejunum. Mean hospital stay after surgery was 6.7 days. Mean follow-up was 5.1 years. No recurrence of the cystic lymphangioma was noticed during follow-up. One case developed an intestinal occlusion due to bowel adhesions 1 year after surgery. CONCLUSIONS: ACL usually affect infants and young children and may present with spectrum of symptoms from an incidental finding to an acute life-threatening abdominal obstruction. Complete excision of the tumor is a safe and effective method in the management of ACL in pediatric population. Surgery is mandatory to avoid potential complications.

Prognostic value of serum CA125 levels in diffuse large B-cell lymphoma: potential role of a new sex- and age-adjusted reference value.

CA125, a tumor marker normally used to follow the clinical course of ovarian cancer, also may have a role in lymphoma. All available series were analyzed using the standard reference value 35 U/ml, but age and sex may influence serum CA125 (sCA125) levels. We aim to study the prognostic value of serum CA125 (sCA125) levels in diffuse large B-cell lymphoma (DLBCL), considering the influence of age and sex on sCA125 levels. We investigated the relationship between sCA125 and clinical outcome after treatment in 42 patients with DLBCL, comparing both the standard (35 U/ml) and a new age and sex adjusted (sex/age-adjusted) reference value proposed by our group. We found that patients with elevated sCA125 levels had significantly more adverse prognostic factors at diagnosis, lower CR rates, higher relapse rates and worse survival. In the low-risk IPI categories, the presence of elevated sCA125 defined a particularly high-risk subgroup with poorer 3-year PFS when compared with patients with normal sCA125 levels. The use of a sex/age-adjusted reference value for sCA125 may increase the sensitivity to identify those patients with elevated sCA125 levels truly related to DLBCL activity.

Photoacclimation in a tropical population of Cladophora glomerata (L.) Kützing 1843 (Chlorophyta) from southeastern Brazil

Photoacclimation of photosynthesis was investigated in a tropical population of C. glomerata (São Paulo State, southeastern Brazil, 20º 48’ 24" S and 49º 22’ 24" W) by chlorophyll fluorescence parameters and chlorophyll a content. Plants were acclimated to two levels of irradiance: low (65 ± 5 µmol.m-2.s-1) and high (300 ± 10 µmol.m-2.s-1) and exposed short-term (4 days) and long-term (28 days) under a light-dark cycle of 12:12 hours. Photosynthesis-irradiance (PI) curves revealed distinct strategies of photoacclimation. In long-term exposure, plants acclimated by altering the photosynthetic units (PSU) number and keeping fixed the PSU size, revealed by increased rates of maximum photosynthesis (Pmax), lower photosynthetic efficiency (alpha) and higher values of the saturation parameter (Ik) under high irradiance. The short-term acclimation strategy consisted of changing the PSU size, with a fixed number of PSUs, as revealed by similar Pmax but higher alpha and lower Ik under low irradiance. Chlorophyll a contents followed the general pattern reported in green algae of higher concentrations under lower irradiance. Dark/light induction curves revealed consistently higher values of potential quantum yield under low irradiance. Initial and final values showed a higher recovery capacity in the short (84.4-90.6 percent) term exposure than in the long-term case (81.4-81.5 percent). ETR (electron transport rate) and NPQ (non-photochemical quenching) values were consistently higher under low irradiance. ETR showed a continuous and steady increase along the light exposure period in the short and long-term experiments, whereas NPQ values revealed a rapid increase after 15 seconds of light exposure, kept a slightly increasing trend and stabilized in most treatments. Lower photosynthetic performance (ETR) and recovery capacity of potential quantum yield were observed, particularly in long-term exposure, suggesting that this population...

A fotoaclimatação da fotossíntese foi investigada numa população tropical de Cladophora glomerata (Estado de São Paulo, sudeste do Brasil, 20º 48’ 24" S e 49º 22’ 24" W) através de parâmetros de fluorescência da clorofila e conteúdo de clorofila a. As plantas foram aclimatadas a dois níveis de irradiância: baixa (65 ± 5 µmol.m-2.s-1) e alta (300 ± 10 :mol.m-2.s-1) e expostas a curto período (4 dias) e longo período (28 dias) em fotoperíodo de 12 horas. Curvas de fotossíntese-irradiância (FI) revelaram estratégias distintas de fotoaclimatação. Plantas expostas a longo período aclimataram pela alteração do número de unidades fotossintéticas (UF) e mantiveram fixo o tamanho das UF. Estas características foram reveladas por menores taxas de fotossíntese máxima (Fmax), menor eficiência fotossintética (alfa) e valores mais altos do parâmetro de saturação (Ik) em alta irradiância. A estratégia de aclimatação em curto período consistiu em mudança no tamanho das UF, com número fixo de UF, conforme revelado por taxas semelhantes de fotossíntese máxima (Fmax), maiores valores de alfa e menores de Ik em baixa irradiância. Os conteúdos de clorofila a seguiram o padrão geral reportado para algas verdes de maiores concentrações em baixa irradiância. Curvas de indução escuro/luz revelaram valores consistentemente mais elevados de rendimento quântico potencial em baixa irradiância. Valores iniciais e finais mostraram capacidade de recuperação mais elevada em curto período (84,4-90,6 por cento) do que em longo período (81,4-81,5 por cento). Os valores da taxa de transporte de elétrons (ETR) e extinção não-fotoquímica (NPQ) foram consistentemente mais elevados em baixa irradiância. Os valores de ETR tiveram aumento contínuo e estável ao longo do período de exposição luminosa em curto e longo períodos, enquanto que os de NPQ revelaram aumento rápido após 15 seconds de exposição à luz, mantiveram leve tendência de aumento e então estabilizaram...

[Haloperidol or droperidol with dexamethasone for antiemetic prophylaxis in laparoscopic cholecystectomy]. / Haloperidol o droperidol asociados a dexametasona como profilaxis antiemética en colecistectomías laparoscópicas.

OBJECTIVES: To compare haloperidol to droperidol, both with dexamethasone, for antiemetic prophylaxis in elective laparoscopic cholecystectomy. MATERIAL AND METHODS: Prospective, randomized double-blind trial enrolling 75 ASA 1-2 patients who received anesthesia with propofol and remifentanil. After induction, 8 mg of intravenous dexamethasone was administered. After surgery, depending on group assignment, patients received 10 microg x kg(-1) of intravenous haloperidol (n = 25), 10 microg x kg(-1) of droperidol (n = 25), or physiologic saline solution (n = 25). Outcomes recorded were episodes of nausea or vomiting in the postoperative period (first 6 hours and/or 6-24 hours), requirement for antiemetic agents, morphine consumption, pain assessed on a visual analog scale, level of sedation, and adverse effects. RESULTS: Five patients in the haloperidol group, 6 in the droperidol group, and 13 in the control group experienced an episode of nausea or vomiting in the 24-hour postoperative period (P < .05 between the active treatment groups and the control group). One patient in the haloperidol group, 6 in the droperidol group, and 8 in the control group reported nausea in the first 6 hours (P < .05). Three patients in the haloperidol group, 1 in the droperidol group, and 8 in the control group reported nausea in the later postoperative period (6-24 hours) (P < .05, droperidol vs control). Three patients in the haloperidol group, 1 in the droperidol group, and 7 in the control group experienced late vomiting (P < .05, droperidol vs control). CONCLUSIONS: Either haloperidol or droperidol in combination with dexamethasone is more effective than dexamethasone alone for antiemetic prophylaxis after laparoscopic cholecystectomy.

Less postoperative nausea and vomiting after propofol + remifentanil versus propofol + fentanyl anaesthesia during plastic surgery.

BACKGROUND: The effect of different opioids on postoperative nausea and vomiting (PONV) has not been conclusively determined yet, thus the aim of this study was to compare the incidence of PONV in propofol-anaesthetized patients receiving either fentanyl or remifentanil as opioid supplement. METHODS: Sixty ASA physical status I and II patients scheduled for plastic surgery gave their written informed consent for this prospective, randomized, double-blind study. Anaesthesia was induced with propofol, rocuronium and fentanyl (n = 30; 2 microg kg(-1)) or remifentanil (n = 30; 1 microg kg(-1)). After tracheal intubation, anaesthesia was maintained with propofol, oxygen in air and an infusion of the opioid studied, which was modified according to clinical criteria. Baseline postoperative analgesia was achieved with intravenous propacetamol + metamizol. Intravenous morphine was given if visual analogic scale (VAS) for pain was > or = 4 (scale 0-10) and metoclopramide was administered if a patient presented > or = 2 PONV episodes (nausea or vomiting) in less than 30 min. Postoperatively (2, 12 and 24 h), we registered VAS, rescue morphine consumption, number of patients with episodes of PONV and number of patients requiring metoclopramide. P < 0.05 was considered significant. RESULTS: There were no significant differences between groups in the demographic parameters, ASA physical status, propofol dose, VAS, and rescue morphine requirements. Fourteen patients in the fentanyl group and four in the remifentanil group presented PONV episodes 2-12 h postoperative hours' interval; (P < 0.05). Ten patients in the fentanyl group and four in the remifentanil group presented vomiting episodes in the same period (P < 0.05); and eight patients in the fentanyl group and one in the remifentanil group required metoclopramide; (P < 0.05). The number of postoperative PONV episodes were low, both in the 0-2-h period (n = 2 vs. n = 1, fentanyl and remifentanil, respectively) and in the 12-24-h period (n = 3 vs. n = 1). CONCLUSION: Propofol + fentanyl anaesthesia resulted in a higher incidence of PONV and requirements of antiemetic drugs in the period between 2 and 12 postoperative hours compared with propofol + remifentanil, in patients undergoing plastic surgery.

Chronic ethanol intoxication enhances the production of cytokine-induced neutrophil chemoattractant and macrophage inflammatory protein-2 by hepatocytes after human immunodeficiency virus-1 glycoprotein 120 vaccination.

Chemokines are implicated in the pathogenesis of alcoholic liver disease and human immunodeficiency virus-1 (HIV-1) infection. Thus, this work examined the regulation of chemokines --i.e., cytokine-induced neutrophil chemoattractant (CINC) and macrophage inflammatory protein-2 (MIP-2)--produced by hepatocytes after HIV-1 glycoprotein 120 (gp120) vaccination in Wistar rats fed with ethanol for 30 weeks. HIV-1 gp120 in complete Freund's adjuvant was given by intrainguinal route at a dose of 5 g/kg, followed by two booster shots in incomplete Freund's adjuvant at a weekly interval. Samples were taken 1 week after the last injection was given. Results show that anti-HIV-1 gp120 antibody titer was suppressed by 40% in the ethanol-fed rats, compared with findings in the parallel controls. However, serum CINC and MIP-2 levels were more elevated in the ethanol-fed rats than in the pair-fed group. The likely sources of these chemokines are the hepatocytes. After HIV-1 gp120 treatment, isolated hepatocytes obtained from the ethanol-fed group produced more CINC and MIP-2 than did those of pair-fed rats. Concomitantly, mRNA expression for these two chemokines and hepatic sequestration of neutrophils were upregulated. Ethanol feeding alone suppressed chemokine release, but it did not alter mRNA expression in isolated hepatocytes. Administration of Freund's adjuvant (without HIV-1 gp120) did not induce chemokine release in vivo and did not prime isolated hepatocytes for enhanced chemokine production in vitro. These results show that chronic ethanol intoxication affects the ability of the host to respond to HIV-1 gp120 vaccination.

Effects of endotoxin on neutrophil-mediated I/R injury in isolated perfused rat hearts.

With the use of a syngeneic model, we demonstrate that rat polymorphonuclear neutrophils (PMNs) exacerbate ischemia-reperfusion injury in the isolated rat heart. However, PMNs (19 x 10(6) cells) from lipopolysaccharide (LPS)-treated rats (LPS-PMNs; 100 mg/kg administered 7 h before exsanguination) induce less reperfusion injury in the isolated heart. Average recovery of left ventricular developed pressure after 20 min of ischemia and 60 min of reperfusion was 51 +/- 4% in hearts receiving PMNs from saline-treated control rats (saline-PMNs) versus 78 +/- 2% in hearts receiving LPS-PMNs. Ischemic hearts reperfused with LPS-PMNs recovered to the same extent as did hearts reperfused with Krebs buffer only. LPS-PMNs and saline-PMNs showed no difference in basal or phorbol ester-induced superoxide production. Whereas twice the number of LPS-PMNs was positive for nitroblue tetrazolium, the percent positive for L-selectin, a receptor integral in PMN-adhesion to endothelium, was 50% less in LPS-PMNs than in controls. After reperfusion, three-fourths of the saline-PMNs remained within the hearts, whereas only one-fourth of LPS-PMNs were trapped. These data suggest that PMNs from LPS-treated rats do not exacerbate ischemia-reperfusion injury as do control PMNs, possibly, due to impaired PMN adhesion to endothelium as a result of decreased L-selectin receptors.

Orthotopic human lung carcinoma xenografts in BALB/c mice immunosuppressed with anti-CD4 monoclonal antibodies and chronic alcohol consumption.

BACKGROUND: The role of the immune system in the surveillance of the body for cancer cells is well established. Human tumor cells do not survive in mice with intact immune systems, but they propagate in athymic nude mice. Presumably, the lack of a thymus gland and consequent loss of T lymphocytes results in a seriously compromised immune system without adequate cell-mediated immunity and tumor surveillance. In patients infected with the human immunodeficiency virus (HIV), a progressive loss of cell-mediated immunity is associated with the development of malignancies and opportunistic infections. This effect may be exacerbated in patients who chronically consume alcohol. METHODS: Normal and alcoholic BALB/c mice were treated with a monoclonal antibody to deplete CD4(+) lymphocytes before orthotopic implantation of human lung adenocarcinoma xenografts. Tumor volume and weight were measured and compared between groups. RESULTS: The authors' data show that a single treatment of anti-CD4 antibody causes almost complete depletion of CD4(+) lymphocytes and permits the formation of large intrapulmonary human nonsmall lung carcinoma xenografts in 100% of treated mice. All control animals injected with heat-denatured antibody failed to produce tumors. Chronic alcohol consumption by CD4-depleted mice resulted in larger tumors, compared with mice that did not receive ethanol in their diet (P = 0.05). CONCLUSIONS: Depletion of CD4(+) lymphocytes allows for the orthotopic growth of human lung adenocarcinoma xenografts in BALB/c mice. Furthermore, the consumption of alcohol reduces the ability of the impaired immune system to reject tumors.

[The treatment of rectorrhagia secondary to postradiation proctitis with 4% formalin]. / Tratamiento de la rectorragia secundaria a proctitis postradiación con formalina al 4%.

Radiation proctitis is a common complication of radiotherapy for pelvic malignancies. In the chronic form it might lead to intractable or massive hemorrhage unresponsive to conventional therapy. In these cases surgery is associated with a high morbidity. Seven female patients previously treated with external beam radiation for carcinoma of the uterus and cervix were included. They had required multiple blood transfusions (median 2), and still had low hemoglobin rates and active hemorrhagic radiation proctitis, were treated. Therapy was accomplished by direct application of gauzes soaked in 4% formalin through the rigid sigmoidoscope or the Pratt anoscope, with the patients under peridural anesthesia. Gauzes were laid in contact with the hemorrhagic surface during 4 minutes and repeated until the bleeding ceased (median total exposure time was 26 minutes). Bleeding ceased immediately in 6 patients, one continued with minor bleeding after formalin treatment, two patients had fever during the first 24 hours which was controlled with physical measures, three patients required repeat formalin application (in external bases), after that six patients had no further bleeding nor was any blood transfusion needed, one patient presented unsuspected sigmoid bleeding stenosis. The formalin therapy is an effective, safe, simple and inexpensive treatment for rectal bleeding caused by radiation proctitis.

Role of Kupffer cells in the ethanol-induced oxidative stress in the liver.

These studies test the hypothesis that acute and chronic alcohol intoxication stimulate the release of oxygen-derived radicals in the liver. Male Sprague-Dawley rats received an intravenous bolus followed by continuous infusion of ethanol to maintain blood alcohol level at about 175 mg/dl for 0-18 hr. They were then allowed to recover from this "alcohol binge" and the release of free radicals during the recovery phase was monitored. In the chronic alcohol intoxication model, rats were fed with 40% ethanol in agar blocks for 16 weeks. Acute ethanol intoxication induced two phases of hepatic superoxide release. The first phase peaked during the first 3 hr of alcohol intoxication, while the second phase reached its maximum at 6 hr of recovery following a 12 hr binge. The recovery period was also associated with elevated serum transaminase activity. Kupffer cells were largely responsible for hepatic superoxide release during the first phase, while both Kupffer and hepatic sinusoidal endothelial cells contributed to the second phase of free radical formation. Acute ethanol intoxication did not induce endotoxemia. During chronic alcohol intoxication, increased levels of serum endotoxin, TNF, IL-1, and transaminase were observed and hepatic superoxide anion release was present. Superoxide release by isolated Kupffer cells, blood and hepatic PMNs of alcoholic rats was also significantly enhanced in the chronic alcoholic rats. These data indicate that acute alcohol intoxication may directly stimulate the release of reactive oxygen intermediates, whereas chronic alcohol may elicit free radical generation through enhanced endotoxin influx and cytokine release. These studies further demonstrate that free radicals produced by hepatic non-parenchymal cells are likely to play an important role in the pathogenesis of hepatic injury in susceptible individuals with alcohol-related liver disorders.

Anti-P30-52 monoclonal antibody cross-reacted to Env V3 and inhibited the viral multiplication of HIV-1-infected MT-4 cells.

It is well known that the anti-p17 antibody titer decreases with the disease progression among human immunodeficiency virus type 1 (HIV-1) carriers. We previously established several murine anti-p17 monoclonal antibodies (MAbs) to investigate the immunological role of p17, and to further characterize these MAbs, we examined the anti-p17 antibody titer in serum of a patient who was a long-term nonprogressor with hemophilia, and found that the antibody for the p17-derivative peptide from amino acid residues 30 to 52 (P30-52) cross-reacted to the third variable region of the envelope glycoprotein of HIV-1, Env V3. In the present study, we primed mice with P30-52 to establish anti-P30-52 MAbs (P30-52 MAbs), and examined their affinity and whether they suppressed the viral multiplication of HIV-1-infected MT-4 (HTLV-1-transformed CD4+ T-cell line) cells, in a TCID50 assay. At the same time, an anti-Env V3 MAb (Env V3 MAb) was also established and examined as above. The IgM-type P30-52 MAb and Env V3 MAb showed heteroclitic binding, and the IgM-type P30-52 MAb inhibited the viral multiplication. We also found that an increase of fragmented DNA of HIV-1-infected MT-4 cells co-cultured with P30-52 MAbs. Because DNA fragmentation is one of the features of programmed cell death, the viral multiplication may be suppressed by the apoptosis of HIV-1-infected MT-4 cells co-cultured with P30-52 MAbs. Though the relationship between cross-reactivity and the inhibition mechanism of multiplication of HIV-1 is unclear, P30-52 of p17 may well be a useful region of viral proteins for the development of therapeutic and vaccination strategies.

[Maze technique for the treatment of auricular fibrillation: initial experience]. / Técnica de MAZE para el tratamiento de la fibrilacion auricular: experiencia inicial.

INTRODUCTION AND OBJECTIVES: The MAZE procedure was developed as a surgical approach to the management of patients with atrial fibrillation refractory to medical treatment. This study seeks to identify the risk and benefits of adding the MAZE procedure in patients with atrial fibrillation undergoing surgery for underlying organic cardiac disorders. MATERIAL AND METHODS: Since november 1993, we have performed 10 interventions with the MAZE procedure, for the treatment of refractory atrial fibrillation. The indication to perform the technique was systemic embolism in 5 patients, contraindication for the anticoagulant treatment in two cases and no response to antiarrhythmic treatment in 5 cases. Two patients had more than one indication. In all the cases another surgical procedure was performed, 5 replacements of mitral valve, a mitral repair, one tricuspid repair and tree repairs of an atrial septal defect. RESULTS: Soon after surgery 9 patients were in sinus rhythm, and one in atrial fibrillation. Four patients needed atrial pacing during the first days. One patient required a pacemaker due to symptomatic sinus bradycardia. During the first 3 months, 4 patients had episodes of paroxysmal atrial fibrillation and flutter. One patient died suddenly one month after surgery. Seven patients have completed two years of follow-up, and are in stable sinus rhythm, in functional class I and free of antiarrhythmic drugs. All of them have echocardiographic evidence of mechanical activity in both atria. Left atrium had been reduced from 5.3 +/- 0.7 cm to 4.5 +/- 0.7 cm (p < 0.05). No patient has presented new embolic events. CONCLUSIONS: The MAZE procedure is a good choice in selected patients with atrial fibrillation refractory to medical treatment, or a precedent of systemic embolism. However, several problems can complicate the patient's course.