Double patch closure of ventricular septal defect with increased pulmonary vascular resistance

BACKGROUND: Closure of a large ventricular septal defect (VSD) in children with elevated pulmonary vascular resistance is associated with significant morbidity and mortality. Pulmonary hypertensive episodes continue to be a major cause of postoperative morbidity and mortality. We designed a fenestrated flap valve double VSD patch in an effort to decrease the morbidity and mortality associated with the closure of a large VSD with elevated pulmonary vascular resistance. METHODS: Eighteen children (mean age, 5.7 years) with a large VSD and elevated pulmonary vascular resistance (mean, 11.4 Wood units) underwent double patch VSD closure using moderately hypothermic cardiopulmonary bypass and cardioplegic arrest. The routine VSD patch was fenestrated (4 to 6 mm) and on the left ventricular side of the patch, a second, smaller patch was attached to the fenestration along its superior margin before closure of the VSD. RESULTS: All children survived operation and were weaned from inotropic and ventilator support within 48 hours postoperatively. Postoperative pulmonary artery pressures were significantly lower than preoperative values. One child died 9 months postoperatively. CONCLUSIONS: Closure of a large VSD in children with elevated pulmonary vascular resistance can be performed with low morbidity and mortality when a flap valve double VSD patch is used.     

Transgenic models in renal tubular physiology

Animal transgenesis has proven to be useful for physiological as well as physiopathological studies. Besides the classical approach based on the random integration of a DNA construct in the mouse genome, gene targeting can be achieved using totipotent embryonic stem (ES) cells for targeted transgenesis. Transgenic mice are then derived from the transgenic ES cells. This allows the introduction of null mutations in the genome (so-called knock-out) or the control of the transgene expression by the endogenous regulatory sequences of the gene of interest (so-called knock-in). Development of these transgenic animals leads to a better understanding of the cellular function of many genes or to the generation of animal models for human diseases. The purpose of this short review is to describe animal models in renal tubular physiopathology. Recent progresses will allow the generation of animal models with conditional expression of the transgene of interest or with a conditional gene mutation. This permits spatial and temporal control of the expression of the transgene or of the mutation. This should allow the generation of models suitable for physiological analysis or closer to disease state.     

Enteropathogenicity markers in Escherichia coli isolated from infants with acute diarrhoea and healthy controls in Rio de Janeiro, Brazil

Faeces from urban children < 2 years old with acute diarrhoeal illness and from non-diarrhoeal infants (controls) were examined for Escherichia coli and other enteropathogens. A total of 990 E. coli isolates from 100 patients and 50 controls was tested for enteropathogenic E. coli (EPEC) serotype (O:H), adherence to HEp-2 cells after incubation for 3 and 6 h, fluorescent actin staining (FAS), DNA hybridisation with EAF, eaeA, STh, STp and EAggEC probes and production of heat-labile enterotoxin (LT) and verocytotoxin (VT) with Y1 and Vero cells. EPEC were the most prevalent enteropathogens in patients (32.7%; and 14% in controls). Enteroinvasive E. coli (EIEC) and Vero cytotoxin-producing E. coli (VTEC) were not detected. The rate of isolation of enterotoxigenic E. coli (ETEC) was identical in both groups. Among the EPEC isolates the prevalent serotypes were O111:H2, O55:NM and O119:H6. Localised adherence (LA) was found significantly more frequently in isolates from patients (19.6%) than controls (2.1%). All LA-positive EPEC isolates were FAS+ and eaeA+, but only 75.2% of them hybridised with the EAF probe. Diffusely adhering E. coli (DAEC) and enteroaggregative E. coli (EAggEC) were found with equal frequency in patients and controls. Twenty-seven E. coli isolates were negative for EAF but positive for eaeA and FAS and produced LA in 6-h adherence tests. These EAF-/eaeA+ strains were the only putative enteropathogen identified in seven patients and were not found in controls. The ability of these strains to elicit ultrastructural cell alterations and cell-signalling events was evaluated in Caco-2 cells (human colon carcinoma cell line) by the gentamicin invasion assay and by transmission electron microscopy. The numbers of intracellular bacteria in cell invasion tests varied from 0.4% to 1.6% of the cell-associated bacteria after a 6-h incubation period. Tyrosine phosphorylation of host cell proteins was assessed in HEp-2 cells by immunofluorescence microscopy and all strains gave positive results. EAF-/eaeA+ E. coli strains express most of the virulence properties found among true EPEC strains and can be a relevant cause of infant diarrhoea in developing countries.     

Partial liquid ventilation reduces pulmonary neutrophil accumulation in an experimental model of systemic endotoxemia and acute lung injury

OBJECTIVE: To determine whether pulmonary neutrophil sequestration and lung injury are affected by partial liquid ventilation with perfluorocarbon in a model of acute lung injury (ALI). DESIGN: A prospective, controlled, in vivo animal laboratory study. SETTING: An animal research facility of a health sciences university. SUBJECTS: Forty-one New Zealand White rabbits. INTERVENTIONS: Mature New Zealand White rabbits were anesthetized and instrumented with a tracheostomy and vascular catheters. Animals were assigned to receive partial liquid ventilation (PLV, n = 15) with perflubron (18 mL/kg via endotracheal tube), conventional mechanical ventilation (CMV, n = 15) or high-frequency oscillatory ventilation (HFOV, n = 5). Animals were ventilated, using an FIO2 of 1.0, and ventilatory settings were required to achieve a normal PaCO2. Animals were then given 0.9 mg/kg of Escherichia coli endotoxin intravenously over 30 mins. Partial liquid ventilation, conventional mechanical ventilation, or high-frequency oscillatory ventilation was continued for an additional 4 hrs before the animals were killed. A group of animals not challenged with endotoxin underwent conventional ventilation for 4.5 hrs, serving as the control group (control, n = 6). Lungs were removed and samples were frozen at -70 degrees C. Representative samples were stained for histology. A visual count of neutrophils per high-power field (hpf) was performed in five randomly selected fields per sample in a blinded fashion by light microscopy. Lung samples were homogenized in triplicate in phosphate buffer, ultrasonified, freeze-thawed, and clarified by centrifugation. Supernatants were analyzed for myeloperoxidase (MPO) activity by spectrophotometry with o-dianisidine dihydrochloride and hydrogen peroxide at 460 nm. MEASUREMENTS AND MAIN RESULTS: Histologic analysis of lung tissue obtained from control animals showed normal lung architecture. Specimens from the PLV and HFOV groups showed a marked decrease in alveolar proteinaceous fluid, pulmonary vascular congestion, edema, necrotic cell debris, and gross inflammatory infiltration when compared with the CMV group. Light microscopy of lung samples of animals supported with PLV and HFOV had significantly lower neutrophil counts when compared with CMV (PLV, 4 +/- 0.3 neutrophils/hpf; HFOV, 4 +/- 0.5 neutrophils/hpf; CMV, 10 +/- 0.9 neutrophils/hpf; p < .01). In addition, MPO activity from lung extracts of PLV and HFOV animals was significantly lower than that of CMV animals (PLV, 61 +/- 13.3 units of MPO activity/lung/kg; HFOV, 43.3 +/- 6.8 units of MPO activity/lung/kg; CMV, 140 +/- 28.5 units of MPO activity/lung/kg; p < .01). MPO activity from lungs of uninjured control animals was significantly lower than that of animals in the PLV, HFOV, and CMV groups (control, 2.2 +/- 2 units of MPO activity/lung/kg; p < .001). CONCLUSIONS: Partial liquid ventilation decreases pulmonary neutrophil accumulation, as shown by decreased neutrophil counts and MPO activity, in an experimental animal model of ALI induced by systemic endotoxemia. The attenuation in pulmonary leukostasis in animals treated with PLV is equivalent to that obtained by a ventilation strategy that targets lung recruitment, such as HFOV.     

Nonsurgical infarctectomy in acute experimental myocardial infarction

This study examines whether a catheter mounted left intraventricular balloon may prevent left ventricular (LV) dysfunction following acute experimental myocardial infarction. In 10 anesthetized pigs, multiple coronary arterial ligations were applied around the apex of the heart. LV end-diastolic pressure (LVEDP), aortic flow (AF), and LV long and short axis fractional shortening (FS) were measured before and at 15 min intervals after ligations. At the 60th min after ligation, the LV long axis FS and AF decreased by 7.2 +/- 2.6% (p < 0.05) and 13.25 +/- 2.68% (p < 0.01), respectively, and the LVEDP increased by 4.3 +/- 1.1 mm Hg (p < 0.01) while no change was noted in the LV short axis FS. An intraventricular catheter mounted nonpulsating balloon was positioned over the endocardium of the infarcted area at the LV apex. Inflation of the nonpulsating balloon to an optimal volume, which was found to be equal to 8-10% of the LV end-diastolic volume, resulted in a reduction (by 3.8 +/- 1.2 mm Hg, p < 0.01) of the already increased LVEDP and in an increase (by 6.6 +/- 2.1%, p < 0.05) in the LV short axis FS while no statistically significant change was noted in the AF and LV long axis FS. It is concluded that an intraventricular catheter mounted balloon patch positioned over the endocardium of the infarcted area may ameliorate early LV dysfunction, possibly by interfering with the functional geometry of the LV contraction.     

Patterns of serial CEA assays and their clinical use in management of colorectal cancer

Through persistent clinical research efforts, the CEA test has developed into a useful although complex disease monitor for colorectal cancer. Although improved or prolonged survival from its use has not been demonstrated, CEA monitoring may allow more knowledgeable patient management. Several reports indicate that postoperative serial CEA assays may identify patients with early recurrence, especially when assays are done frequently. Patients with elevated pretreatment CEA levels usually showed progressively rising titers before other objective evidence of recurrence was apparent. A progressively rising CEA titer correlated well with recurrent cancer, but a normal CEA could not be used as proof of its absence. Persistently elevated CEA titers post-treatment was caused either by persistent disease or by nontumor-related factors. The CEA assay was not a substitute for clinical follow-up but was an adjunct in the diagnosis of eary recurrence. Patients with elevated CEA levels caused by localized disease treated by radiation therapy demonstrated a marked fall in serial CEA levels if all CEA-producing tumor was localized within the radiation portal. The use of pretreatment CEA values plus the pattern of CEA reponse to irradiation may help in the selection of fulguration versus abdominoperineal resection as primary treatment for rectal cancer. Persistently low serial CEA titers after irradiation therapy correlated with disease control. The use of frequent serial CEA assays in patients treated with chemotherapy compared well with other parameters as a monitor of disease progression or regression. When used with other clinical parameters, serial CEA trends appeared to be a useful adjunct in assessing the effectiveness of chemotherapy. A fall in circulating CEA or the stabilization of a rising titer after starting chemotherapy usually indicated an effective regimen, whereas a rising CEA titer may signal may signal the need to initiate or to change chemotherapy.