Role of glutamine administration on cellular immunity after total parenteral nutrition enriched with glutamine in patients with systemic inflammatory response syndrome

Glutamine is an important substrate for enterocyte and other rapidly proliferating cells. Low plasma and tissue levels present in glutamine in critically ill patients suggest that demand may exceed endogenous supply. Because commercially available amino acid solutions do not contain glutamine because of its instability in aqueous solution, conventional total parenteral nutrition (TPN) does not prevent stress-induced glutamine depletion. In this study, we administered intravenous glutamine-supplemented TPN to patients with systemic inflammatory response syndrome (SIRS) to investigate the effect of glutamine supplementation on immune states. This study is a prospective, randomized clinical trial. All patients received TPN given continuously for 6 days. Thirty patients with SIRS were allocated to either a glutamine group (l-glutamine 0.4g/[kg d]) (n = 15) or a control group (n = 15). Blood samples were collected on day 1 and day 6 after admission for C-reactive protein, immunoglobulin (Ig) M, IgG, IgA, C₃, C4, and lymphocyte analysis. The Acute Physiologic and Chronic Health Evaluation II score and the Simplified Acute Physiologic II (SAPS II) score were used to evaluate the patients after admission. Although there was a tendency for decreased T cytotoxic cells and natural killer cells in the control group, no significant difference was observed between the 2 groups. However, an increase in lymphocyte and lymphocyte subgroups in the glutamine group was observed; but there was no difference between the groups. A low SAPS II score was observed on the sixth day in the glutamine group, whereas no difference in SAPS II and Acute Physiologic and Chronic Health Evaluation II scores was observed between the 2 groups. There was no difference in IgM, IgG, IgA, C₃, and C4 levels and numbers of B-lymphocytes between the groups. Glutamine-added TPN significantly decreases leukocyte and natural killer cell count and therefore suppresses inflammation. Furthermore, total lymphocyte count, B- and T-lymphocytes, and their subgroups (helper T-lymphocytes, cytotoxic T-lymphocytes) are increased; although not statistically significant, these increases might be playing a role in improving the immune system.     

Bestatin administration and the change in cellular immunity

The change in cellular immunity by Bestatin (ubenimex) treatment--30 mg/day orally--was investigated in 23 gastrointestinal cancer patients for: 1), functional T cell subsets; 2), IL-2 receptor; 3), PHA-induced blastogenesis; and 4), PPD skin reaction. The absolute number of helper T cells (Th) and cytotoxic T cells (Tc) increased in 74 and 79% of cases, respectively, compared with pretreatment values. On the other hand, the absolute number of suppressor T cells (Ts) decreased in 79% of cases. IL-2 receptor increased in 56% of patients, PHA blastogenesis increased in 67% of patients and PPD skin reaction was elevated in 75% of cases comparing to pretreatment values. These results suggest that Bestatin could increase cellular immunity in cancer patients.     

Catheter-associated UTIs in patients after major gynaecological surgery

A group of nurses undertook an audit across two hospitals comparing the incidence of catheter-related urinary tract infections in patients who had catheters inserted during major gynaecological surgery. The data suggests that using an anaesthetic lubricating gel for catheterisation reduces urinary tract infection rates for these patients.     

肝外胆管结石手术对人免疫缺陷病毒感染者细胞免疫的影响

目的观察肝外胆管结石外科手术对不同免疫缺陷程度的肝胆结石患者细胞免疫功能的影响。方法统计36例人免疫缺陷病毒(Human immunodeficiency virus,HIV)阳性(HIV+)与同期42例HIV阴性(HIV-)共78例需行外科手术的肝外胆管结石患者术后切口感染、术后肺部感染、术后新发机会性感染等指标。检测其术前1天(D0)、术后第7天(D7)、术后第30天(D30)外周静脉血白细胞计数、中性粒细胞率、淋巴细胞率、T淋巴细胞亚群CD4、CD8计数;各自计算D7、D30两次CD4计数相对于D0百分比D7/D0(%)、D30/D0(%).并根据D0的CD4计数分层(组)。结果各组三次检测白细胞计数、中性粒细胞率、淋巴细胞率、CD8计数差异无统计学意义(P>0.05);CD4计数两两比较差异有统计学意义(P<0.05);不同组别之间差异有统计学意义(F=402.410,P<0.05);时间和组别两个因素之间有交互效应(F=13.497,P<0.05)。结论肝外胆管结石外科手术对以CD4为主的细胞免疫功能有"先抑制后恢复"的影响过程,HIV感染者免疫缺陷程度越重,其免疫抑制越明显,免疫恢复也更缓慢。正确把握手术适应证以及恰当的围术期处理前提下,合并HIV感染的肝外胆管结石患者施行手术可以取得与非HIV感染者类似满意的临床疗效.     

Connective tissue response to major surgery and postoperative infection

Type I and type III collagen are components of a healing wound, and major structural proteins. According to our previous study, wound fluid concentrations of the liberated propeptide extensions of procollagens can be used to monitor collagen synthesis in the wound. Serum concentrations of the carboxyterminal propeptide of type I procollagen (PICP), and the aminoterminal propeptide of type III procollagen (PIIINP) were studied here for up to half a year in 102 patients, admitted for major abdominal surgery. In a frequent follow-up (n = 9), one minimum and two maxima were found for S-PICP, occurring 1 day, 7 days, and 2 months after surgery, respectively. S-PIIINP had a minimum at 1 day and a peak at 10 days. Relative changes (follow-up result/pre-operative concentration) of the propeptides in 50 uncomplicated patients were compared. The 1-day minimum of S-PICP was 0.60 (SD 0.18), and that of S-PIIINP 0.89 (0.27), (P less than 0.0001, 95% CI for the mean difference 0.21 to 0.36). The 7-day peak of S-PICP was 1.4 (0.5), and that of S-PIIINP 2.5 (1.2), (P less than 0.0001, CI 0.81 to 1.42). The 2-month-peak of S-PICP was 1.6 (0.3), and at the same time the relative S-PIIINP was still 1.7 (0.3) without any separate peak. Major infectious (n = 8) and other (12) complications, exploratory procedures (22) and patients with abnormal pre-operative propeptide levels (8) were studied separately. Two early deaths were excluded. Only major infection had a remarkable effect on the responses of S-PICP (3/8) and S-PIIINP (5/8).(ABSTRACT TRUNCATED AT 250 WORDS)     

Plasma concentrations but not serum concentrations of brain-derived neurotrophic factor are related to pro-inflammatory cytokines in patients undergoing major abdominal surgery

ObjectivesTo investigate peripheral brain-derived neurotrophic factor (BDNF) concentrations in the perioperative period, their relationship with transforming growth factor-β1 (TGF-β1 tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-6 genetics.Design and methodsProspective, observational study. BDNF, TGF-β1, IL-6 and TNF-α were analysed at baseline (T0), 5 h (T1), 24 h (T2) and 5 days (T3) after surgery, in 21 patients. The IL-6 ? 174 G/C polymorphism was genotyped.ResultsSerum BDNF concentrations decreased (P = 0.048), correlated with TGF-β1 (r = 0.610 at T1, r = 0.493 at T2, r = 0.554 at T3). Plasma BDNF concentrations raised (P = 0.049), correlated with IL-6 and TNF-α at T1 (r = 0.495 and r = 0.441, respectively). BDNF response was predictable from TNF-α and IL-6 concentrations and the IL-6 ? 174 G/C genotype.ConclusionSerum and plasma BDNF concentrations could relate to platelet activation and inflammatory response, respectively. IL-6 genetics played a role in the BDNF acute response.     

Hyaluronan-modified and regular multilamellar liposomes provide sub-cellular targeting to macrophages, without eliciting a pro-inflammatory response

Macrophages, pivotal cells in onset and progression of inflammation, can benefit from sub-cellular drug targeting to the molecular loci of drug action, whether cell membrane or cell interior. Postulating manipulation of liposome size and surface properties can provide sub-cellular targeting, we studied: thermodynamics of liposome-macrophage binding; liposome cellular localizations; liposome safety including pro-inflammatory cytokine production. We aimed at extending the body of knowledge on interactions of regular unilamellar (RL-ULV) and multilamellar (RL-MLV) liposomes with macrophages. We investigated, for the first time, the interactions of hyaluronan (HA) surface-modified liposomes (HA-ULV and HA-MLV) with macrophages, with respect to multiple equilibria binding combined with cellular localization. Macrophages bound all four liposome types, substantially-favoring the two MLV species over the two ULV species, and internalizing only RL-MLV. Three macrophage-internalization inhibitors (2-deoxyglucose, LY294002 and Wortmannin) reduced RL-MLV internalization but not binding affinity nor binding capacity. Both MLV types were not detrimental to cell proliferation, nor did they elicit TNF-α production in resting and in LPS-activated macrophages. Moreover, a 24-hour exposure of LPS-activated macrophages to HA-MLV reduced TNF-α production by 40%, indicating potential for anti-inflammatory activity. In conclusion RL-MLV and HA-MLV are the liposomes of choice for delivering anti-inflammatory drugs to the macrophage surface or its interior, according to the loci of drug action.     

Theophylline-induced alterations in cellular immunity in asthmatic patients

Twenty patients with bronchial asthma, on long-term oral therapy with theophylline, demonstrated an increased number of suppressor T-cells and impaired graft vs host reaction. Ten asthmatics on other therapy, not including theophylline, as well as ten normal healthy controls, failed to show similar findings. Elimination of suppressor T-cells corrected the above immunological abnormalities in the theophylline-treated patients, while addition of serum from theophylline-treated asthmatic patients to lymphocytes from normal healthy controls, affected the graft vs host reaction of these lymphocytes. We conclude that theophylline induces quantitative as well as qualitative immunological alterations by increasing the number and activity of suppressor T-cells, which most probably secrete a serum factor, responsible for some of the abnormalities observed.     

Local cellular and humoral immunity in pneumonia patients

The paper reports a study of some local immunity factors in pneumonia aimed at specification of mechanisms inducing respiratory immunodeficiency and their effects on the disease course. Local cellular immunity of the lungs was studied by estimation of the total number of cells in the bronchoalveolar lavage, their viability, alveolar macrophages (AM), neutrophils, T- and B-lymphocytes, AM and neutrophil phagocytic index and number, receptor apparatus. The lavage IgA, IgM, IgG, lysozyme were estimated. It was found that local cellular and humoral immunity depend on clinicoetiological form of pneumonia. Cellular and humoral immunodeficiency was the greatest in staphylococcal infection. The role of cellular and humoral immunity dysfunction in the lungs in genesis of bronchoobstructive syndrome is specified. Recovery of cellular and humoral immunity in pneumonia reconvalescents is behind clinical recovery. Grave immunodeficiency in severe or lingering pneumonia may be a pathogenetic factor of chronic inflammation in the lungs. To evaluate functional condition of local immunity of the lungs it is valid to study cellular and humoral factors of local pulmonary immunity in bronchoalveolar lavage.     

门静脉置管注射中西药对慢性乙肝患者细胞免疫功能影响的探讨

目的探讨经门静脉注射药物治疗慢性乙型肝炎的可行性,观察门静脉置管注射中西药对慢性乙型肝炎患者细胞免疫功能的影响。方法8例肝癌术后的慢性乙型肝炎患者,于肝癌手术时皮下埋置药盒门静脉内置管,向药盒内注入胸腺肽40mg,黄芪注射液10ml。治疗前后用流式细胞术绝对计数T淋巴细胞及其亚群、自然杀伤细胞(NK),并观察其副反应。结果治疗前后CD3665.63±434.80个/μlvs1326.50±551.09个/μl,CD3 CD8 275.63±205.78个/μlvs513.50±231.00个/μl,CD3 CD4 515.88±329.75个/μlvs981.75±478.54个/μl,NK细胞130.86±176.58个/μlvs303.43±190.90个/μl,差异具有显著性意义(P<0.05),除1例中度发热、4例轻度发热外,无其他副反应。结论胸腺肽与黄芪合用可增强慢性乙肝患者的细胞免疫功能。经门脉注射药物可能成为乙肝治疗的新途径,应加大样本进一步研究。     

Massive transfusion without major complications after trauma

A case of massive degloving injury of the trunk, with open pelvic fracture, and evisceration of abdominal contents from blunt trauma is presented. The most significant aspect of this case was the transfusion of 173 units of packed cells and 176 units of fresh frozen plasma in the first thirty hours. The patient ultimately recovered and returned to work.     

The epidemiology of rapid response team activation amongst patients undergoing major gastrointestinal surgery

BackgroundClinical deterioration requiring rapid response team (RRT) review is associated with increased morbidity amongst hospitalised patients. The frequency of and association with RRT calls in patients undergoing major gastrointestinal surgery is unknown. Understanding the epidemiology of RRT calls might identify areas for quality improvement in this cohort.ObjectivesThe objective of this study is to identify perioperative risks and outcome associations with RRT review following major gastrointestinal surgery.MethodsWe conducted a retrospective cohort study using electronic databases at a large Australian university hospital. We included adult patients admitted for major gastrointestinal surgery between 1 January 2015 and 31 March 2018.ResultsOf 7158 patients, 514 (7.4%) required RRT activation postoperatively. After adjustment, variables associated with RRT activation included the following: hemiplegia/paraplegia (odds ratio [OR]: 8.0, 95% confidence interval [CI]: 2.3 to 27.8, p = 0.001), heart failure (OR: 6.9, 95% CI: 3.3 to 14.6, p < 0.001), peripheral vascular disease (OR: 5.3, 95% CI: 2.7 to 10.4, p < 0.001), peptic ulcer disease (OR: 4.2, 95% CI: 2.2 to 8.0, p < 0.001), chronic obstructive pulmonary disease (OR: 4.0, 95% CI: 2.2 to 7.2, p < 0.001), and emergency admission status (OR: 2.6, 95% CI: 2.1 to 3.3, p < 0.001). Following the index operation, 46% of first RRT activations occurred within 24 h of surgery and 61% had occurred within 48 h. The most common triggers for RRT activation were tachycardia, hypotension, and tachypnoea. Postoperative RRT activation was associated with in-hospital mortality (OR: 6.7, 95% CI: 3.8 to 11.8, p < 0.001), critical care admission (incidence rate ratio: 8.18, 95% CI: 5.23 to 12.77, p < 0.001), and longer median length of hospital stay (12 days vs. 2 days, p < 0.001) compared to no RRT activation.ConclusionAfter major gastrointestinal surgery, one in 14 patients had an RRT activation, almost half within 24 h of surgery. Such activation was independently associated with increased morbidity and mortality. Identified associations may guide more pre-emptive management for those at an increased risk of RRT activation.     

Persistent cellular immunity to SARS-CoV-2 infection

SARS-CoV-2 is responsible for an ongoing pandemic that has affected millions of individuals around the globe. To gain further understanding of the immune response in recovered individuals, we measured T cell responses in paired samples obtained an average of 1.3 and 6.1 mo after infection from 41 individuals. The data indicate that recovered individuals show persistent polyfunctional SARS-CoV-2 antigen–specific memory that could contribute to rapid recall responses. Recovered individuals also show enduring alterations in relative overall numbers of CD4⁺ and CD8⁺ memory T cells, including expression of activation/exhaustion markers, and cell division.     

Clinical evaluation of alternative-site glucose measurements in patients after major cardiac surgery

OBJECTIVE: Tight glycemic control improves outcome in critically ill patients but requires frequent glucose measurements. Subcutaneous adipose tissue (SAT) has been characterized as promising for glucose monitoring in diabetes, but it remains unknown whether it can also be used as an alternative site in critically ill patients. The present study was performed to clinically evaluate the relation of glucose in SAT compared with arterial blood in patients after major cardiac surgery. RESEARCH DESIGN AND METHODS: Forty critically ill patients were investigated at two clinical centers after major cardiac surgery. Arterial blood and SAT microdialysis samples were taken in hourly intervals for a period of up to 48 h. The glucose concentration in dialysate was calibrated using a two-step approach, first using the ionic reference technique to calculate the SAT glucose concentration (SATg) and second using a one-point calibration procedure to obtain a glucose profile comparable to SAT-derived blood glucose (BgSAT). Clinical validation of the data was performed by introducing data analysis based on an insulin titration algorithm. RESULTS: Correlation between dialysate glucose and blood glucose (median 0.80 [interquartile range 0.68-0.88]) was significantly improved using the ionic reference calibration technique (SATg vs.blood glucose 0.90 [0.83-0.94]; P < 0.001). Clinical evaluation of the data indicated that 96.1% of glucose readings from SAT would allow acceptable treatment according to a well-established insulin titration protocol. CONCLUSIONS: The results indicate good correlation between SATg and blood glucose in patients after major cardiac surgery. Clinical evaluation of the data suggests that with minor limitations, glucose from SAT can be used to establish tight glycemic control in this patient group.     

Effects of prenalterol on renal function in patients after major vascular surgery

Hemodynamic and renal effects of prenalterol were studied in 13 mechanically ventilated patients on the first day after major vascular surgery. Prenalterol (1-[4-hydroxyphenoxy]-3-isopropylamino-2 propanol hydro-chloride), a partial beta-agonist with a predominant beta-1 and a weak beta-2-adrenoceptor activity, was infused into seven patients at rates of 0.5 and 1.0 microgram/kg.min (group A), and at a dose of 2.0 micrograms/kg.min in six patients (group B). Although no hemodynamic changes were observed in group A, systolic BP, mean BP, heart rate, and cardiac output increased significantly in group B. Catecholamine levels and plasma renin activity were unaltered in both groups, as was glomerular filtration rate. Renal blood flow did not change in group A but it increased by 25% in group B. Urine flow, fractional free water clearance, fractional sodium excretion, and fractional chloride excretion were unaltered in both groups. Fractional potassium excretion decreased by 20%, 22%, and 26% at the three infusion rates of prenalterol, respectively. We conclude that prenalterol does not directly influence renal function in the postoperative setting.