Intravenous glutamine decreases lung and distal organ injury in an experimental model of abdominal sepsis

Introduction

The protective effect of glutamine, as a pharmacological agent against lung injury, has been reported in experimental sepsis; however, its efficacy at improving oxygenation and lung mechanics, attenuating diaphragm and distal organ injury has to be better elucidated. In the present study, we tested the hypothesis that a single early intravenous dose of glutamine was associated not only with the improvement of lung morpho-function, but also the reduction of the inflammatory process and epithelial cell apoptosis in kidney, liver, and intestine villi.

Methods

Seventy-two Wistar rats were randomly assigned into four groups. Sepsis was induced by cecal ligation and puncture surgery (CLP), while a sham operated group was used as control (C). One hour after surgery, C and CLP groups were further randomized into subgroups receiving intravenous saline (1 ml, SAL) or glutamine (0.75 g/kg, Gln). At 48 hours, animals were anesthetized, and the following parameters were measured: arterial oxygenation, pulmonary mechanics, and diaphragm, lung, kidney, liver, and small intestine villi histology. At 18 and 48 hours, Cytokine-Induced Neutrophil Chemoattractant (CINC)-1, interleukin (IL)-6 and 10 were quantified in bronchoalveolar and peritoneal lavage fluids (BALF and PLF, respectively).

Results

CLP induced: a) deterioration of lung mechanics and gas exchange; b) ultrastructural changes of lung parenchyma and diaphragm; and c) lung and distal organ epithelial cell apoptosis. Glutamine improved survival rate, oxygenation and lung mechanics, minimized pulmonary and diaphragmatic changes, attenuating lung and distal organ epithelial cell apoptosis. Glutamine increased IL-10 in peritoneal lavage fluid at 18 hours and bronchoalveolar lavage fluid at 48 hours, but decreased CINC-1 and IL-6 in BALF and PLF only at 18 hours.

Conclusions

In an experimental model of abdominal sepsis, a single intravenous dose of glutamine administered after sepsis induction may modulate the inflammatory process reducing not only the risk of lung injury, but also distal organ impairment. These results suggest that intravenous glutamine may be a potentially beneficial therapy for abdominal sepsis.     

Wegener's Granuloma. A Series of 265 British Cases Seen Between 1975 and 1985. A Report by a Sub-committee of the British Thoracic Society Research Committee

In order to describe the British experience of Wegener's granuiomatosisHospital Activity Analysis was used to collect cases diagnosedin England, Wales and Scotland between 1975 and 1985. Wherepossible clinical details, histological material and chest radiographswere obtained. Two hundred and sixty five patients were consideredto have Wegener's granuiomatosis. In 109 a single pathologistconfirmed the diagnosis by finding both granulomas and vasculitisin biopsy material. The diagnosis was made on clinical groundsor clinical grounds together with histological diagnosis inthe local hospital in 156 patients. Wegener's granuiomatosiswas confined to the lung or upper respiratory tract in 22 percent of patients and renal disease occurred in 58 per cent.Laboratory tests showed a pattern of mild anaemia, polymorphleucocytosis, eosinophilia and an elevated ESR and hypergammaglobulinaemia,with no specific pattern of changes. Histological confirmation was most frequently obtained by examinationof nasal biopsy specimens, but multiple biopsies were oftenrequired. Renal biopsies showed focal proliferative glomerulonephritisbut granulomatous glomerulonephritis was uncommon. Of availablechest radiographs 61 per cent were abnormal, large opacitiesbeing most common. Small irregular opacities were found lessoften and other abnormalities were uncommon. Treatment varied widely and 10 per cent of patients receivedno drug therapy. This large series illustrates that even withoutspecific treatment, patients with Wegener's granuiomatosis cansurvive for several years and with modern treatment survivalfor more than a decade is possible. Conclusions about the effectivenessof the various therapies cannot be drawn from this restrospectivestudy. Renal failure and disseminated vasculities were the commonestcauses of death; death was considered to result from complicationsof treatment with cytotoxic drugs or prednisolone in 6 per centof patients.     

A Gastroesophageal Electrode for Atrial and Ventricular Pacing

Temporary transvenous cardiac pacing requires technical expertise and access to fluoroscopy. We have developed a gastroesophageal electrode capable of atrial and ventricular pacing. The flexible polythene gastroesophageal electrode is passed into the stomach under light sedation. Five ring electrodes, now positioned in the lower esophagus, are used for atrial pacing. A point source (cathode) on the distal tip of the electrode, now positioned in the gastric fundus. is used for ventricular pacing. Two configurations of atrial and ventricular pacing were compared: unipolar and bipolar. During unipolar ventricular pacing the indifferent electrode (anode) was a high impedance chest pad. For bipolar ventricular pacing the indifferent electrode was a ring electrode placed 2 cm proximal to the tip. Unipolar atrial pacing was performed with 1 of 5 proximal ring electrodes acting as cathode ("cathodic") or as anode ("anodic") in conjunction with a chest pad. Bipolar atrial pacing was performed using combinations of 2 of 5 ring electrodes. Atrial capture was obtained in all 55 subjects attempted. When all electrode combinations were compared, atrial capture was significantly more frequent using the bipolar approach (153/210 bipolar, 65/210 unipolar; t = 7.37, P < 0.001). For unipolar atrial pacing, cathodic stimulation (from esophagus) was more successful than anodic stimulation (cathodic 62/105, anodic 20/105; t = 5.81, P < 0.001). In 43 subjects attempted unipolar ventricular pacing resulted in a higher frequency of capture than the bipolar approach (unipolar 41/43 (95.3%), bipolar 19/43 (44.2%); P < 0.001). In conclusion, atrial pacing was optimal using pairs of ring electrodes ("bipolar") while ventricular pacing was optimal using the distal electrode tip (cathode) in conjunction with a chest pad electrode ("unipolar"). This gastroesophageal electrode may be useful in the emergency management of acute bradyarrhythmias and for elective electrophysiological studies.     

The impact of balloon angioplasty of coronary artery and/or vein bypass graft lesion(s) upon the survival of patients >= 5 years after their last bypass surgery

Data analyses of angioplasty patients, whose operative and angioplasty(PTCA) intervalwas 5 years, were performed to determine ifthe site of PTCA (coronary artery (CA) and/or vein bypass graft(VG)) influenced longevity. PTCA was successful in 677/768 lesions(88%) (377/432 CA (87%), and 294/327 VGs (90%)) and resultedin clinical improvement in 280/322 patients (87%). Patientswere stratified into those who underwent PTCA of a lesion(s)in a coronary artery only, a vein graft only, or in both a coronaryartery and a vein graft. Survival, at 60 months, was adverselyaffected (P<0.05) for VG (59%) in comparison to CA (86%)or CA $ VG (86%) cohorts, which was reaffirmed by a Cox proportionalhazard model. PTCA was effective in opening lesions in coronary arteries orvein grafts in patients whose last bypass surgery had occurredover 5 years previously; however, PTCA patients who only hada vein graft had a significantly diminished 5-year survivalin comparison to the cohorts, who had a coronary artery lesiondilated, with or without an accompanying vein graft PTCA. Therefore,PTCA of isolated vein graft lesions may not be the best long-termtherapeutic option for these patients; however, it may bestserve patients, acutely and long-term, who have an emenablesignificant arterial lesion, whether or not an accompanyingvein graft lesion is dilated.     

Postoperative Heart Block in Children with Common Forms of Congenital Heart Disease: Results from the KID Database

Postoperative Heart Block in Congenital Heart Disease. Introduction: Cardiac conduction system injury is a cause of postoperative cardiac morbidity following repair of congenital heart disease (CHD). The national occurrence of postoperative complete heart block (CHB) following surgical repair of CHD is unknown. We sought to describe the occurrence of and costs related to postoperative CHB following surgical repair of common forms of CHD using a large national database. Methods and Results: Retrospective, observational analysis performed over a 10‐year period (2000–2009) using the Kids’ Inpatient Database (KID). Visits for patients ≤24 months of age were identified who underwent surgical repair of ventricular septal defects (VSD), atrioventricular canal defects (AVC), and tetralogy of Fallot (TOF). Patients were identified who were diagnosed with postoperative CHB, further identifying those requiring a new pacemaker placement during the same hospitalization. Costs associated with visits were calculated. There were 16,105 surgical visits: 7,146 VSD, 3,480 AVC, and 5,480 TOF. There was a decrease in postoperative mortality (P = 0.0001) with no significant change in postoperative CHB. Hospital stay and cost were higher with CHB and placement of a permanent pacemaker. Repair of AVC (OR 1.77; [1.32–2.38]) was associated with a higher rate of postoperative CHB. Length of hospital stay and total cost were significantly increased with the development of postoperative CHB and increased further with placement of a permanent pacemaker. Conclusion: There has been little change over time in the frequency of postoperative CHB in patients undergoing repair of VSD, AVC, and TOF. Postoperative CHB results in major added cost to the healthcare system. (J Cardiovasc Electrophysiol, Vol. 23, pp. 1349‐1354, December 2012)     

<Emphasis Type="Italic">CYP2C19</Emphasis> and <Emphasis Type="Italic">ABCB1</Emphasis>gene polymorphisms are differently distributed according to ethnicity in the Brazilian general population

Background  

Recent studies have reported the clinical importance of CYP2C19 and ABCB1 polymorphisms in an individualized approach to clopidogrel treatment. The aims of this study were to evaluate the frequencies of CYP2C19 and ABCB1 polymorphisms and to identify the clopidogrel-predicted metabolic phenotypes according to ethnic groups in a sample of individuals representative of a highly admixtured population.     

DOES TESTOSTERONE AFFECT THE NORMAL MENSTRUAL CYCLE?

In order to throw further light on the role of androgens in the aetiology of the polycystic ovary syndrome (PCO) we have examined the effect of artificially increasing serum testosterone levels on menstrual function in a group of ovulating women. Six women were studied who had either severe premenstrual syndrome or loss of libido for which they were treated with 100 mg testosterone by s.c. implantation. All had regular menstrual cycles. For 1 month before implantation serum LH, FSH, oestradiol (E2), progesterone and testosterone were measured three times per week. All women showed normal cyclical variation of LH, FSH, E2 and progesterone. Following implantation, three times weekly blood samples were taken during the first and third cycles. No patient had any disturbance of menstrual pattern. All continued to show cyclical changes of LH, FSH, E2 and progesterone. Serum E2 and progesterone were lower but not significantly so in the luteal phase of the treated cycles. This was despite a mean serum testosterone which rose from 1.3 to 7.1 nmol/l at the end of the third week following implantation and to 4.1 nmol/l at the end of the third month. Sex hormone binding globulin levels fell as expected by 18.5% during the first cycle. The lack of significant effect of a markedly elevated serum testosterone level on cyclical hormone changes is indirect evidence that in PCO the primary cause of the menstrual disturbance is not excessive production of ovarian or adrenal testosterone.     

IgMs produced by two acquired immune deficiency syndrome lymphoma cell lines: Ig binding specificity and VH-gene putative somatic mutation analysis [published erratum appears in Blood 1994 Aug 1;84(3):995]

Two B-cell lines, 2F7 and 10C9, were established by single cell cloning from biopsies obtained from two acquired immune deficiency syndrome patients with Burkitt's lymphoma. Representation of the original tumors was verified by demonstration of (1) identical biallelic rearrangement of Ig genes for 2F7 and (2) shared idiotype for 10C9. Both cell lines displayed cell-surface Ig and secreted Ig (IgM lambda for 2F7, IgM kappa for 10C9). IgMs from both cell lines immunoprecipitated actin; in addition, 2F7 IgM lambda immunoprecipitated recombinant human immunodeficiency virus type 1 (HIV-1) gp 160. 2F7 IgM lambda did not react with other autoantigens (double-stranded and single-stranded DNA, actin, bovine serum albumin, IgG), whereas 10C9 IgM kappa reacted with human IgG. The 2F7 IgM heavy-chain variable region (VH) showed a 95% nucleotide homology with a previously sequenced VHIII germline gene, hv3019b9, whereas the 10C9 IgM VH showed a 95% homology with a previously sequenced VHIV germline gene, VH4.21. Use of minimally modified VH genes and demonstration of reactivity with chronically present antigens (ie, actin, HIV-1 gp 160, or human IgG) suggests that B cells in HIV-1-infected individuals proliferating in response to chronic antigenic stimulation may be at increased risk for lymphomagenesis.