Mesna protects splanchnic organs from oxidative stress induced by pneumoperitoneum

Background  We investigated the potential beneficial effect of the antioxidant 2-mercaptoethane-sulfonate (mesna) against oxidative stress induced by pneumoperitoneum in splanchnic organs. Methods  Wistar rats were subjected to either (a) CO₂ pneumoperitoneum (15 mmHg for 60 min) (group P), (b) pretreatment with mesna (400 mg/kg, p.o.) followed by pneumoperitoneum with a 180 min interval (group MP), (c) sham operation (group S), or (d) administration of mesna only (group M). Forty-five minutes after desufflation (groups P and MP), 60 + 45 min after the induction of anesthesia (group S), or 180 min after mesna administration (group M), tissue specimens were excised from liver, kidneys, jejunum and stomach. Tissue oxidative state was assessed on the basis of glutathione-to-glutathione disulfide ratio, malondialdehyde concentration , and superoxide dismutase activity. Results  Pneumoperitoneum deteriorated all the oxidative stress markers in the organs studied. Mesna prevented the occurrence of oxidative stress following pneumoperitoneum in all the organs studied. In the absence of pneumoperitoneum, the administration of mesna caused mild enhancement of the oxidative state of liver, stomach, and kidneys compared to sham controls. Conclusions  Prophylaxis with mesna prevents oxidative stress induced by pneumoperitoneum in splanchnic organs.     

Absence of mutations in the <Emphasis Type="Italic">HOXA11</Emphasis> and <Emphasis Type="Italic">HOXD11</Emphasis> genes in children with congenital renal malformations

Experimental studies have shown that homeobox genes are essential for the development of the kidney and urinary tract. Hoxa11/Hoxd11 double mutant mice demonstrate renal agenesis or hypoplasia. Since, to our knowledge, these genes have never been examined for alterations in humans with congenital anomalies of the kidney and urinary tract (CAKUT), we investigated whether mutations of HOXA11/HOXD11 genes are associated with non-syndromal congenital renal parenchymal malformations. DNA samples from 26 unrelated children with unilateral renal agenesis (URA), 20 with renal hypodysplasia (RHD) and 13 with multicystic dysplastic kidney (MCDK) were included in the study. Exons 1 and 2 of the HOXA11/HOXD11 genes were amplified individually by polymerase chain reaction (PCR) using 12 unique oligonucleotide primers. Single-strand conformation polymorphism (SSCP) analysis of overlapping polymerase chain reaction products was performed. SSCP analysis revealed no variant band shifts in the samples of the amplified segments of the 59 patients, suggesting lack of either mutation or polymorphisms. Our findings do not support the hypothesis that mutations in the HOXA11/HOXD11 coding regions are involved in the pathogenesis of human non-syndromal congenital renal parenchymal malformations. Further studies are necessary, since other genes known to affect nephrogenesis, as well as genetic and environmental factors, may be involved.     

SIV-specific CD8+ T cells express high levels of PD1 and cytokines but have impaired proliferative capacity in acute and chronic SIVmac251 infection

Programmed death-1 (PD-1) is a critical mediator of virus-specific CD8+ T-cell exhaustion. Here, we examined the expression of PD-1 on simian immunodeficiency virus (SIV)-specific CD8+ T cells and its possible involvement in regulation of cytokine production, proliferation, and survival of these cells. The majority of SIV-specific CD8+ T cells expressed a PD-1(high) phenotype, independent of their differentiation status, in all tissues tested. PD-1 expression gradually declined on CD8+ T cells specific for SIV-derived epitopes that had undergone mutational escape, indicating that antigen-specific TCR stimulation is the primary determinant of PD-1 expression. SIV-specific PD-1(high)CD8+ T cells produced IFN-gamma, TNF-alpha, and IL-2 under cognate peptide stimulation. While CD8+ T cells that proliferated in response to antigen had a PD-1(high) phenotype, it was determined that there was a reduced proliferative capacity of PD-1(high) compared with PD-1(low) SIV-specific CD8+ T cells. PD-1(high) SIV-specific CD8+ T cells were highly susceptible to cell death leading to loss of such cells after in vitro stimulation. Thus, PD-1 is a negative regulator of SIV-specific CD8+ T cells, operating predominantly through the induction of cell death. Manipulation of the interaction of PD-1 with its ligands could thus potentially restore the CD8+ T-cell responses in SIV infection.     

Time-dependent changes in the expression of thyroid hormone receptor alpha 1 in the myocardium after acute myocardial infarction: possible implications in cardiac remodelling

The present study investigated whether changes in thyroid hormone (TH) signalling can occur after acute myocardial infarction (AMI) with possible physiological consequences on myocardial performance. TH may regulate several genes encoding important structural and regulatory proteins particularly through the TR alpha 1 receptor which is predominant in the myocardium. AMI was induced in rats by ligating the left coronary artery while sham-operated animals served as controls. This resulted in impaired cardiac function in AMI animals after 2 and 13 weeks accompanied by a shift in myosin isoforms expression towards a fetal phenotype in the non-infarcted area. Cardiac hypertrophy was evident in AMI hearts after 13 weeks but not at 2 weeks. This response was associated with a differential pattern of TH changes at 2 and 13 weeks; T(3) and T(4) levels in plasma were not changed at 2 weeks but T(3) was significantly lower and T(4) remained unchanged at 13 weeks. A twofold increase in TR alpha 1 expression was observed after 13 weeks in the non-infarcted area, P<0.05 versus sham operated, while TR alpha 1 expression remained unchanged at 2 weeks. A 2.2-fold decrease in TR beta 1 expression was found in the non-infarcted area at 13 weeks, P<0.05, while no change in TR beta 1 expression was seen at 2 weeks. Parallel studies with neonatal cardiomyocytes showed that phenylephrine (PE) administration resulted in 4.5-fold increase in the expression of TR alpha 1 and 1.6-fold decrease in TR beta 1 expression versus untreated, P<0.05. In conclusion, cardiac dysfunction which occurs at late stages after AMI is associated with increased expression of TR alpha 1 receptor and lower circulating tri-iodothyronine levels. Thus, apo-TR alpha 1 receptor state may prevail contributing to cardiac fetal phenotype. Furthermore, down-regulation of TR beta 1 also contributes to fetal phenotypic changes. alpha1-adrenergic signalling is, at least in part, involved in this response.     

Clinical considerations and therapeutic strategy for sigmoid volvulus in the elderly： A study of 33 cases

AIM: To evaluate different types of treatment for sigmoid volvulus and clarify the role of endoscopic intervention versus surgery. METHODS: A retrospective review of the clinical presentation and imaging characteristics of 33 sigmoid volvulus patients was presented, as well as their diagnosis and treatment, in combination with a literature review. RESULTS: In 26 patients endoscopic detorsion was achieved after the first attempt and one patient died because of uncontrollable sepsis despite prompt operative treatment. Seven patients had unsuccessful endoscopic derotation and were operated on. On two patients with gangrenous sigmoid, Hartmann's procedure was performed. In five patients with viable colon, a sigmoid resection and primary anastomosis was carried out. Three patients had a lavage "on table" prior to anastomosis, while in the remaining 2 patients a diverting stoma was performed according to the procedure of the first author. Ten patients were operated on during their first hospital stay (3 to 8 d after the deflation). All patients had viable colon; 7 patients had a sigmoid resection and primary anastomosis, 2 patients had sigmoidopexy and one patient underwent a near-total colectomy. Two patients (sigmoidectomy-sigmoidopexy) had recurrences of volvulus 43 and 28 mo after the initial surgery. Among 15 patients who were discharged from the hospital after non-operative deflation, 3 patients were lost to follow-up. Of the remaining 12 patients, 5 had a recurrence of volvulus at a time in between 23 d and 14 mo. All the five patients had been operated on and in four a gangrenous sigmoid was found. Three patients died during the 30 d postoperative course. The remaining seven patients were admitted to our department for elective surgery. In these patients, 2 subtotal colectomies, 3 sigmoid resections and 2 sigmoidopexies were carried out. One patient with subtotal colectomy died. Taken together of the results, it is evident that after 17 elective operations we had only one death (5.9%), whereas after 15 emergency operations 6 patients died, which means a mortality rate of 40%. CONCLUSION: Although sigmoid volvulus causing intestinal obstruction is frequently successfully encountered by endoscopic decompression, however, the principal therapy of this condition is surgery. Only occasionally in patients with advanced age, lack of bowel symptoms and multiple co-morbidities might surgical repair not be considered.     

Circumflex femoral vein thrombosis misinterpreted as acute hamstring strain

The case of a 24-year-old female professional, long-distance runner who presented with acute proximal posterior thigh pain is reported. History and clinical findings were consistent with acute hamstring strain but MRI demonstrated circumflex femoral vein thrombosis. This is the first case of proximal posterior thigh pain caused by circumflex femoral vein thrombosis reported in the literature. Doctors dealing with sports injuries should be aware of this clinical entity that mimics hamstring strain.     

Damage control surgery in the abdomen: an approach for the management of severe injured patients

Damage control is well established as a potentially life-saving procedure in a few selected critically injured patients. In these patients the 'lethal triad' of hypothermia, acidosis, and coagulopathy is presented as a vicious cycle that often can not be interrupted and which marks the limit of the patient's ability to cope with the physiological consequences of injury. The principles of damage control have led to improved survival and to stopped bleeding until the physiologic derangement has been restored and the patient could undergo a prolong operation for definitive repair. Although morbidity is remaining high, it is acceptable if it comes in exchange for improved survival. There are five critical decision-making stages of damage control: I, patient selection and decision to perform damage control; II, operation and intraoperative reassessment of laparotomy; III, resuscitation in the intensive care unit; IV, definitive procedures after returning to the operating room; and V, abdominal wall reconstruction. The purpose of this article is to review the physiology of the components of the 'lethal triad', the indication and principles of abdominal damage control of trauma patients, the reoperation time, and the pathophysiology of abdominal compartment syndrome.     

The contribution of conventional nuclear molecular imaging in characterising the nature of a growing solitary pulmonary nodule. Report of a case

The solitary pulmonary nodule (SPN) is a relatively common imaging finding, often representing a diagnostic challenge. Radiological appearance, growth rate calculation during follow up and probability of malignancy assessment by the Bayes' theorem are widely used for identifying the nature of a SPN. Molecular imaging by fluoro-18 deoxy glucose positron emission tomography has revolutionised non-invasive diagnosis of lung cancer, but the low-cost, widely available conventional nuclear imaging modalities still remain valid in the field. We present a case of a growing SPN in a middle-aged male smoker. Growth rate assessment by sequential computed tomography scans, over a follow up period of five years, was suggestive of benign histology, while Bayesian analysis warranted histological confirmation of the nodule's nature. Imaging by both labelled somatostatin analogue technetium 99m-depreotide ((99m)Tc-depreotide) and thallium 201-chloride was almost exclusive of malignancy. The nodule was excised and histology showed a pulmonary hamartoma. We briefly discuss the relative role of invasive and non-invasive methods, with emphasis in conventional radionuclide molecular imaging, for the identification of the nature of SPN.     

The contribution of acute cholecystitis, obesity, and previous abdominal surgery on the outcome of laparoscopic cholecystectomy

The aim of this study was to evaluate the impact of acute cholecystitis (AC), obesity, and previous abdominal surgery on laparoscopic cholecystectomy (LC) outcomes. Records of 1940 patients undergoing LC in 1992 and 2004 were reviewed in order to assess the independent and joint effects of the above risk factors on conversion, morbidity, operation time, and hospital stay. In multivariate regression analysis, adjusting for sex and age, AC alone and in combination with obesity or previous abdominal surgery increased the risk of conversion and complications and was associated with prolonged operation time and hospital stay compared with the patients without any of the risk factors (reference group). The independent and joint effects of obesity and previous abdominal surgery were significant only on operation time. On the contrary, previous upper abdominal surgery alone and in combination with AC was associated with 3- and 17-fold relative odds of conversion, respectively. The combined presence of AC, obesity, and previous abdominal surgery yielded an odds ratio for conversion of 7.5 and for complications of 10.7, as well as a longer operation time and hospital stay. The presence of previous upper abdominal surgery with AC and obesity had a substantial effect on conversion, with an odds ratio of 87.1 compared with the reference group. LC is safe in patients with AC, previous abdominal surgery, or obesity. However, the presence of inflammation alone or in combination with obesity and/or previous (especially upper) abdominal surgery is the main factor that influences the adverse outcomes of LC.     

Diagnosis and management of substernal Goiter at the University of Crete

The objective of this work was to evaluate the diagnosis and management of patients with substernal goiter (SSG) on the basis of our experience. We conducted a retrospective study of all SSGs within a series of 591 thyroidectomies performed in a tertiary referral center over a period of 14 years, analyzing epidemiological data, diagnostic criteria, and surgical results. There were 37 (6%) patients with descending goiter: 28 women (mean age 57.1 years) and 9 men (mean age 61 years). All 37 patients underwent successful surgical treatment without any major postoperative complications. A postoperative histological examination revealed a 16.6% incidence of malignancy. Despite the size and close proximity to vital organs in the mediastinum, all of the SSGs were managed successfully. A neck approach was used in all except for one patient who was operated on via sternotomy. A thorough preoperative evaluation including computed tomography scan of the neck and mediastinum, and an appropriate surgical technique ensure a positive outcome for most patients with an SSG.