Subhamay Ghosh

Carbon monoxide: Endogenous mediator, potential diagnostic and therapeutic target

Abstract The primary objectives of this article are to review the potential role of carbon monoxide (CO) as an endogenous mediator, diagnostic marker for pulmonary disorders, and therapeutic target in critical illness. The review will start by focusing on the importance of the heme oxygenase (HO)-CO axis as an endogenous system as it relates to the cardiovascular and pulmonary systems. It will elucidate the influence of HO gene expression on critical events like shock, sepsis, ischemia-reperfusion and others. Our focus will then shift and look at the potential diagnostic role of exhaled CO in major inflammatory states of the lung, and finally we will highlight the activities on inhaled CO being considered as a possible therapeutic tool and the controversies surrounding it.

Effect of glutamine in patients with esophagus resection.

UNLABELLED Glutamine is the most abundant amino-acid in the extra- and intracellular compartments of the human body, which accounts for over 50% of its free amino-acid content. Utilization of glutamine peptides is explicitly useful, resulting in a decrease in the number of postoperative infectious complications, period of hospitalization, and therapeutic costs. This article aims to study the effects of glutamine on systemic inflammatory response, morbidity, and mortality after esophagectomy. A prospective, randomized, double-blind, and controlled trial was used. Following sealed-envelope block randomization, the patients were divided into two groups. Members of the glutamine group (group G) received glutamine (Dipeptiven, Fresenius) as continuous infusion for 6 hours at 0.5 g/kg for 3 days prior to, and 7 days following surgery; while patients of the control group were given placebo. We examined 30 patients in group G, and 25 patients as controls. In both patient groups, the levels of total protein, albumin, pre-albumin, retinol binding protein, transferrin, transferring-saturation, C-reactive protein, procalcitonin, lymphocte, Interleukin-6, Interleukin-8, tumor necrosis factor alpha, and serum lactate were determined prior to surgery (t(0)), directly after surgery (t(u)), following surgery on day 1 (t(1)), day 2 (t(2)), and day 7 (t(7)). For statistical analysis Mann-Whitney U test and chi-square test were used. There was no significant difference between the two groups regarding age, male/female ratio, and SAPS II scores. Intensive care unit morbidity and mortality was similar in both groups (group G: 24 survivors/6 nonsurvivors; CONTROL 17 survivors/8 nonsurvivors; P= 0.607). Daily Multiple Organ Dysfunction Score did not differ significantly between the two groups. The observed inflammatory markers followed the pattern we described without significant difference. Based on our study, the glutamine supplementation that we used had no influence on morbidity, mortality, or postoperative inflammatory response after esophagectomy.

Time course of platelet aggregation during thrombolytic treatment of massive pulmonary embolism.

We studied changes in platelet aggregation and fibrinogen levels during thrombolysis with massive or submassive pulmonary embolism. Fifteen patients were randomized into ultrahigh-dose streptokinase (UH-SK n = 8) or alteplase (tPA n = 7) groups. Arterial blood samples were taken before and after thrombolysis every 4 h between 4 and 36 h, and once daily between 2 and 30 days. In-vitro platelet aggregation was examined as spontaneous (0.9% NaCl) and induced aggregation with adrenaline 10 μmol/l, collagen 2 μg/ml and ADP 10 μmol/l. D-dimer and fibrinogen were measured every 8 h on first day, and later as above. In the UH-SK group, adrenaline-induced platelet aggregation decreased at 4 and 8 h compared with baseline (P < 0.03). Adrenaline-induced platelet aggregation was significantly lower in the UH-SK group than in the tPA group at 36 h and on day 3 (P < 0.03). Platelet aggregation induced by ADP was lower at 4 h than at baseline in the UH-SK group (P < 0.05). Collagen-induced platelet aggregation was lower at 4 and 8 h than at baseline (P < 0.05) in the UH-SK group. Compared with baseline, fibrinogen levels decreased in both groups after thrombolysis. D-dimer levels were elevated in both groups at 8 h (tPA group, P < 0.0004; UH-SK group, P < 0.05). Spontaneous platelet aggregation, major bleeding or re-embolism was not documented. Platelet aggregation decreased after thrombolysis with UH-SK for 12 h, in comparison tPA caused an insignificant decrease. Fibrinogen level decreased with UH-SK treatment for 5 days but in case of tPA we could not measure significant changes. According to our findings, tPA is a more suitable drug but streptokinase is also effective because of its cost–benefit ratio.

Increases in circulating matrix metalloproteinase-9 levels following fibrinolysis for acute pulmonary embolism.

INTRODUCTION Fibrinolyis is one of the first line therapies in high risk pulmonary embolism (PE) according to current guidelines. Previous studies showed that fibrinolytic therapy with tPA (tissue plasminogen activator, or alteplase) upregulates the concentrations of matrix metalloproteinases (MMPs) and contributes to hemorrhagic transformation after cardioembolic stroke. However, no previous study has described the circulating MMPs levels following fibrinolysis for acute PE. MATERIALS AND METHODS We serially measured the circulating levels of MMPs (MMP-9 and MMP-2) and their endogenous inhibitors, the tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 in alteplase and in streptokinase-treated patients with acute PE by gelatin zymography and by enzyme-linked immunosorbent assays, respectively. RESULTS We found that therapy of PE streptokinase or with alteplase is associated increased pro-MMP-9, but not MMP-2, concentrations for up to 24hours, whereas no significant changes were found in TIMP-1 or TIMP-2 concentrations. This alteration returned to normal 3 to 5days after thrombolysis. This is the first study reporting on MMPs alterations following fibrinolysis for acute PE. CONCLUSIONS We found transient increases in circulating pro-MMP-9 levels following fibrinolysis for acute PE. Our findings support the hypothesis that increased MMP-9 levels may underlie the risk of intracerebral hemorrhage or other bleeding complication of thrombolysis for acute PE, and the use of MMP inhibitors may decrease such risk.

Anesthetics impact on cancer recurrence: What do we know?

Surgery is an important component of treatment in cancer patients. However, surgical stress, anesthesia, and perioperative analgesia interfere with the host immune defense mechanisms and may contribute to metastatic dissemination of malignant tumors and cancer progression. Little is known about the effects of anesthesia on tumor recurrence. In vivo studies and clinical data show some evidence that regional anesthesia is beneficial for cancer patients as it may decrease the risk of metastasis. This short review summarizes the clinical data on the possible association between anesthesia, perioperative analgesia, and the risk of cancer recurrence. Most of the clinical reports are based on retrospective studies, and properly designed prospective trials including a sufficient number of patients is required to reveal the interaction of various anesthetic drugs and methods and cancer progression.

Kinetics of inflammatory markers following cancer-related bowel and liver resection.

Abstract Background. Macrophage migration inhibitory factor (MIF) was originally described as a cytokine that inhibits migration of macrophages at the site of inflammation. Subsequently it was also identified as a stress-induced hormone released from the anterior pituitary lobe in response to some pro-inflammatory stimuli like endotoxins and tumour necrosis factor (TNF-α). Aim. To compare postoperative changes in serum MIF levels of patients undergoing bowel and liver resections. It has clinical relevance to describe the kinetics of this crucial mediator of systemic inflammation in surgery. Methods. A total of 58 patients were studied over 4 years. Group A (28 patients) underwent only hepatic resection without enterotomy. Group B (30 patients) had bowel resection with enterotomy. MIF, IL-1β, IL-8, prealbumin, albumin, α1-glycoprotein, fibrinogen, and C-reactive protein levels were measured preoperatively, immediately following surgery, and postoperatively for three consecutive days. To evaluate organ functions, multiple organ dysfunction score was used. Results. A significantly higher level of MIF (4,505 pg/mL) was found in group A when compared to that of group B immediately following surgery. Other parameters monitored in this study were not statistically different between the two groups. Conclusion. Higher elevations in MIF levels with liver resections, compared to bowel resections, might be attributable to MIF release from damaged liver cells. The presumably minimal endotoxin exposure during bowel surgery was either insufficient or inefficient to induce relevant MIF elevations in our patients. To fully delineate implications of this finding further studies are needed.

Anaesthetic Considerations for Patients with Severe Aortic Stenosis

Valvular heart disease has significant effect on the outcome of practically any kind of surgical procedure involving general or regional anaesthesia. The most frequently encountered cardiac valve lesions produce pressure overload (mitral stenosis, aortic stenosis) or volume load (mitral regurgitation, aortic regurgitation) on the left atrium or left ventricle. Anaesthetic management during the perioperative period is based on the likely effects of drug induced changes in cardiac rhythm, heart rate, preload, afterload, myocardial contractility, systemic blood pressure, systemic vascular resistance and pulmonary vascular resistance relative to the pathophysiology of the heart disease.[1]

Pathophysiology, Diagnosis and Treatment of Pulmonary Embolism Focusing on Thrombolysis - New approaches

1.1 Incidence and mortality of pulmonary embolism Pulmonary embolism (PE) is not a disease by itself but may have a venous thrombotic source and is therefore more precise if classified as venous thromboembolism (VTE). According to the international registry, the frequency of VTE is 150-200 new cases diagnosed per 100,000 inhabitants per year. Out of this, one third is diagnosed as primary PE (Oger, 2000; Walther et al., 2009). Following the diagnosis the average mortality is 11% in the first two months (Goldhaber et al., 1999). In the ICOPER study, the total mortality of PE in the first 3 months was 17.5%. However, in the long run the recurrent embolic episodes and lack of revascularisation caused progressive pulmonary hypertension (Goldhaber et al., 1999). The mortality of untreated PE is 30% and with adequate treatment can be reduced to 2-8% (Goldhaber, 1998). The hospital mortality of haemodynamically stable PE patients is overall 10% in general, 4% in the first 24 hours (Kline et al., 2003). Mortality of PE with respiratory and cardiovascular failure on hospital admission can be up to 95%. Hospital mortality is 80% in patients requiring mechanical ventilation and 77% in those who need cardiopulmonary resuscitation in the first 24 hours (Janata et al., 2002). Only 29% of fatal PE cases (verified at hospital autopsies) were previously diagnosed clinically. Based on these facts, the primary goal in PE management is a rapid and clear diagnosis followed by the appropriate treatment (S. Buchner & Th. Hachenberg, 2005).

Direct Effects of Chemoradiotherapy following Esophagectomy

Background: Esophageal cancer is a major cause of morbidity and mortality, but despite continuing research, few effective therapies have been identified. In recent years, surgical resection following chemoradiotherapy has been associated with improved survival in several clinical models. Aim: In a prospective, observational study, we evaluated the direct effects of chemoradiotherapy on postoperative mortality, morbidity, and inflammatory response in patients following esophagectomy. Methods: The study cohort was divided into two groups: the first group received preoperative chemoradiotherapy, while the second group had surgical intervention without prior treatment. Nutritional status was evaluated for the members of both patient groups at various time points. Results: Preoperative chemoradiotherapy did not influence morbidity or organ function, and the postoperative inflammatory response did not show immunosuppressive side effects directly after surgery. Conclusion: Preoperative chemoradiotherapy does not improve postoperative organ function, inflammatory response or nutritional status in the patients. These findings may help to improve outcome in patients with esophageal cancer in the future.