Cardiac troponin I release and cytokine response during experimental human endotoxaemia

Objective To study the relationship between cytokine levels and cardiac troponin I (cTnI).Design Prospective experimental study.Setting Intensive care unit of a university hospital.Participants Six healthy male volunteers.Interventions Endotoxin, 4 ng/kg, was given as a 1-min intravenous infusion.Measurements and results Circulating cardiac troponin I levels and proinflammatory cytokines tumour necrosis factor- (TNF-), interleukin-6 (IL-6) and interleukin-8 (IL-8) were analysed at various time points during a 24-h period. TNF- appeared in the circulation 30 min after injection (T=0.5 h), reaching peak levels (5,665±1,910 pg/ml) 2 h after infusion. At T=24 h TNF- was still elevated in the circulation compared to T=0. None of the six volunteers had a cTnI value higher than 0.1 g/l at T=0, 6 h or 24 h.Conclusion The presence of significant amounts of TNF-, IL-6 and IL-8 in the systemic circulation does not lead to increased levels of cTnI in experimental human endotoxaemia.     

Intracavitary therapy of neoplastic effusions with cytokines: comparison among interferon α, β and interleukin-2

Preliminary studies have suggested that the intracavitary administration of cytokines may represent a new effective palliative therapy of malignant effusions. To define further the therapeutic role of cytokines in the treatment of neoplastic fluid accumulation, 70 cancer patients with pleural, pericardial or peritoneal cytologically proven neoplastic effusions were randomized to receive intracavitary cycles with interleukin-2 (IL-2; 6x10⁶ IU), interferon (IFN; 2x10⁷ U) or IFN (6x10⁶ U) every week for 2 or 3 weeks. A clinical control of fluid accumulation was obtained in 39/70 (56%) patients. In patients with mesothelioma, the response rate was significantly higher with IL-2 than with IFN or-, while there was no difference in patients with tumors other than mesothelioma. Moreover, the duration of the period during which drainage was not required was significantly longer in patients treated with Il-2 than in the other groups. Toxicity was low in all patients. According to preliminary data, this study demonstrates that intracavitary administration of cytokines, including IL-2, IFN and-, is a new well-tolerated palliative therapy for malignant effusions, with an efficacy substantially comparable to that described with the most commonly used treatments with tetracyclines or cytostatic agents.     

Cytokine and coagulation characteristics of retrieved blood after arthroplasty

Objectives To investigate cytokine and coagulation/fibrinolysis characteristics in blood retrieved from wounds using an autotransfusion system, and to compare the cytokine pattern in the retrieved blood with those in the systemic circulation and in the initial portion of drainage blood from the wound.Design Prospective controlled clinical study.Setting The postoperative ward of a University hospital.Patients and participants Blood retrieval was performed over a period of 4–6 h on patients who had just undergone arthroplasty (nine hips, one knee). In five other cases involving hip arthroplasties, the initial portion of drainage blood was studied.Measurements and results Coagulation/fibrinolysis parameters were analyzed in blood retrieved using the Stryker Consta Vac system. Concentrations of tumor necrosis factor (TNF), interleukin-1 (IL-1) and interleukin-6 (IL-6) were analyzed in the retrieved blood, in the systemic circulation of the patients at the beginning and at the end of blood retrieval and in the initial portion of drainage blood from the surgical area. In the retrieved blood, the activities of thrombin, kallikrein and plasmin were increased, antithrombin and free protein S were decreased, and in all samples IL-6 was >1000 pg/ml. Postoperative plasma concentrations of IL-6 rose from a median value of 0 to 116 pg/ml (p<0.01). Four patients had circulating TNF concentrations (range: <15–50 pg/ml). Plasma IL-1 was not detected. TNF and IL-1 were detected in all samples of initial blood from the surgical area and IL-6 in one sample.Conclusion Hypercoagulability and high concentrations of IL-6 were present in the retrieved blood. The cytokine pattern in the initial portion of blood from the surgical area differed from those in the retrieved blood and in the systemic circulation.     

Influence of surgical intervention in the immune response of severely injured patients

Objective Primary events such as severe injury and elective surgery cause a deterioration of the immune response measurable by reduction of expression of HLA-DR on monocytes or ex vivo LPS-induced TNF production. The further influence of secondary surgery after severe injury on the immune response remains unresolved.Design Prospective observation study.Setting Surgical intensive care unit of an university hospital.Patients Sixteen severely injured patients with an ISS >25 points.Measurements and results On day 1 after trauma and immediately before secondary surgery, mean fluorescence intensity (MFI) of HLA-DR expression on monocytes and TNF ex vivo synthesis was significantly reduced compared to healthy donors. Overall, surgical intervention during the second week after trauma caused no further reduction of HLA-DR expression on monocytes and of the ex vivo TNF-synthesis. However, major surgery such as intramedullary nailing or pelvic osteosynthesis caused reduction of the HLA-DR expression and TNF-synthesis, whereas, minor surgical interventions such as osteosynthesis on peripheral joints exhibited no significant effects on the immune response. Surgical intervention performed to clear septic foci normalised immune response by elevating HLA-DR expression on monocytes and ex vivo TNF synthesis. Severe injury caused elevated serum IL-10 levels, whereas secondary surgery did not induce a further increase in serum IL-10 levels.Conclusion This study shows that initial trauma as well as major secondary surgery causes a suppression of immune functions, whereas minor secondary surgery does not cause significant immune disturbance.     

Immune monitoring of patients with septic shock by measurement of intraleukocyte cytokines

Objective To assess the immune competence of patients presenting with septic shock by measuring on-line the production of intracellular cytokines by circulating leukocytes.Design and setting Prospective study in a 18-bed medical intensive care unit of a university hospital.Patients and participants 21 patients with septic shock, and 11 volunteers.Interventions Single-step isolation of leukocytes from whole blood obtained within the first 24 h after admission. Leukocytes were fixed immediately or after treatment with lipopolysaccharide (LPS) and/or heterologous plasma.Measurements and results Leukocytes were permeabilized, and the intracellular cytokine expression of TNF- and IL-10 was quantified by immunostaining and flow cytometry. LPS treatment significantly increased monocyte intracellular cytokine TNF- and IL-10 as well as lymphocyte intracellular cytokine IL-10 in normal leukocytes. Septic monocytes and granulocytes had nonstimulated intracellular cytokine TNF- concentrations lower than those measured in volunteers and were severely hyporesponsive to LPS. These phenotypic changes were correlated with disease severity and could be reproduced by treatment of normal leukocytes with plasma from patients with septic shock.Conclusions Intracellular cytokine staining is a simple and rapid method to assess in situ and on-line the inflammatory balance and responsiveness of leukocyte subpopulations and could therefore represent a useful monitoring tool to assess the immune competence of critically ill patients. This study identifies the cellular source of cytokines in whole blood and confirms prior reports showing that septic phagocytes are characterized by a predominant anti-inflammatory phenotype, with hyporesponsiveness to LPS, depending on a plasma deactivation factor.     

Opsonophagocytic dysfunction in patients with liver cirrhosis and low responses to tumor necrosis factor-α and lipopolysaccharide in patients’ blood

To evaluate their defense level against bacterial infection of patients with liver cirrhosis, we compared the luminol-dependent chemiluminescence (CL) response of peripheral blood from 40 patients with that from 40 healthy volunteers. Small quantities of heparinized whole blood (100µl; final dilution, 1:10) were used for phagocytes, and CL was measured on addition of nonopsonized zymosan or Escherichia coli without special opsonization. Whole blood CL in cirrhotic patients was significantly lower than that in the healthy controls. The incidence of lower CL response in patients increased as disease stage advanced. Polymorphonuclear leukocytes (PMN) from cirrhotic patients exibited a slightly lower CL response than those from controls, but this was not statistically significant. In contrast, the CL response of monocytes in patients was significantly lower than that of controls. The opsonizing capacity of the patients sera and ascitic fluid was also decreased. In fact, the levels of opsonins such as complement in the patients sera and both immunoglobulins and complement in the ascitic fluids were found to be lower in cirrhotic patients. On the basis of these findings, defect of opsonophagocytic function seems to participate in the increased susceptibility to infection in cirrhotic patients. Furthermore, whole blood CL induced by nonopsonized zymosan at the onset of relatively severe bacterial infections such as sepsis, pneumonia, or spontaneous bacterial infection was less augmented in the blood of cirrhotic patients than that in noncirrhotic patients. To clarify the reason why whole blood exhibits a lower CL response in the acute phase of bacterial infections, we investigated the priming effects of lipopolysaccharide (LPS) or tumor necrosis factor- (TNF-), well-known CL activators, on the CL response of whole blood obtained from cirrhotic patients in comparison with that from healthy persons. The priming effects were significantly decreased in patients blood when compared with that of healthy persons. These low responses of patients blood to LPS or TNF- support our finding that phagocytes are not fully activated when gram-negative bacterial infections occur.     

Antibiotic-mediated release of tumour necrosis factor alpha and norharman in patients with hospital-acquired pneumonia and septic encephalopathy

Objective To investigate antibiotic-mediated release of tumour necrosis factor (TNF)- and norharman in patients with hospital-acquired pneumonia with and without additional septic encephalopathy.Design Prospective observational study with a retrospective post hoc analysis.Setting Surgical intensive care unit (ICU) at a university hospital.Patients Thirty-seven patients were consecutively included (9 patients with hospital-acquired pneumonia, 11 patients with hospital-acquired pneumonia and septic encephalopathy, 17 control patients) in the study. Pneumonia was defined according to the criteria of the American Thoracic Society.Interventions Patients received cephalosporins for antibiotic treatment of hospital-acquired pneumonia. Blood samples were taken before, immediately after and 4 h after application of cephalosporins.Measurements and results Of the pneumonia patients, 55% developed septic encephalopathy. ICU stay, complications and mortality were significantly increased. An increased release of TNF- was immediately seen in all pneumonia patients after antibiotics compared to controls, whereas the level did not differ between patients with and without septic encephalopathy. Norharman was significantly increased in pneumonia patients 4 h after antibiotic treatment, in tendency more enhanced in the pneumonia patients without encephalopathy.Conclusions Patients with hospital-acquired pneumonia and septic encephalopathy had a significantly longer ICU stay with higher mortality rate compared to patients with hospital-acquired pneumonia alone. Antibiotic-mediated TNF- release may induce the kynurenine pathway. TNF- activates indolamine-2,3-dioxygenase with neurotoxic quinolinic acid as the end product. Norharman seems to counteract this mechanism and seems to play a role in neuroprotection. The worse outcome of patients with encephalopathy expresses the need to investigate protective factors and mechanisms.     

Human leukocyte antigen-DR expression in peripheral blood mononuclear cells from healthy donors influenced by the sera of injured patients prone to severe sepsis

Objective To study the influence of sera from severely injured patients on the human leukocyte antigen (HLA)-DR expression of normal peripheral blood mononuclear cells (PBMC).Design In vitro study.Setting University hospital.Patients and participants Sera from 34 patients were obtained within 8 h after trauma. Seventeen of these patients developed posttraumatic sepsis (sepsis group) and 17 recovered without infectious complications. Sera from ten healthy individuals served as controls. Phytohemagglutinin (PHA)-activated PBMC from 44 healthy donors were used to study the effects of a patient's serum.Measurements and results Medium containing 5% of serum from the sepsis group significantly (p<0.05) reduced the HLA-DR expression (channels, mean ± standard error of the mean) on monocytes (patients 883±22, controls 962±15), B (patients 922±14, controls 972±7) and T cells (patients 932±13, controls 968±5) of PHA-activated PBMC. Significantly increased accumulation of TNF on (1.8±0.4% of PBMC) and within T cells (0.98±0.26% of PBMC) was observed by flow cytometry after incubation with medium containing sera of the sepsis group compared with controls (on 0.5±0.1%, within 0.27±0.05% of PBMC). A significant negative correlation between relative cell counts of intracellular TNF-positive T cells with HLA-DR expression was observed for monocytes (r= –0.61), B cells (r= –0.57) and proliferation (r= –0.68) as estimated by ³H-thymidine uptake [patients 139,971±12,844 counts per minute (cpm), controls 198,973±19,347 cpm, p<0.05] in the presence of sera from the sepsis group.Conclusions Reduced cellular immunity and, therefore, immunodeficiency after trauma appears to be caused by soluble factors influencing T cell function in particular.     

Prevention of cytokine-induced hypotension in cancer patients by the pineal hormone melatonin

Hypotension is a frequent side-effect of cancer biotherapies with cytokines. Cytokine-induced hypotension would mainly depend on the stimulation of nitric oxide (NO) production, which represents the most effective endogenous vasodilator. Moreover, it has been proven that both biological activity and toxicity of cytokines are influenced by the psychoneuroendocrine system, in particular by the pineal hormone melatonin. To investigate the possible modulatory effect of melatonin on cytokine cardiovascular toxicity, we evaluated the influence of a concomitant melatonin administration on interleukin-2(IL-2)- and tumour-necrosis-factor-(TNF)-induced hypotension in advanced cancer patients. The study included 116 patients with advanced solid tumour, for whom no effective standard anticancer therapy was available, who underwent cancer biotherapy with IL-2 (3 × 10⁶ IU/day s.c. every day, 6 days/week for 4 weeks) or with TNF (0.75 mg/day i.v. for 5 days) as compassionate treatment for their disease. Patients were randomized to be treated with or without a concomitant melatonin administration (40 mg/day orally in the evening, starting 7 days prior to cytokine injection). The occurrence of hypotension was significantly less frequent in patients concomitantly treated by melatonin than in those who received the cytokine alone, during either IL-2 or TNF immunotherapy (IL-2: 11/45 versus 2/46,P<0.05; TNF: 10/23 versus 1/12,P<0.01). This study shows that melatonin may prevent hypotension occurring during cancer immunotherapy with IL-2 or TNF. Since the pineal hormone has appeared to inhibit the activity of NO synthase from the endothelial cells, we suggest that melatonin may prevent cytokine-induced hypotension by inhibiting NO production, which plays an essential role in inducing hypotension during IL-2 and TNF biotherapies.     

Reversible “locked-in” syndromes

Two young patients are described who made good recoveries from a locked-in syndrome presumed to be due to ventral pontine ischemia. The first patient recovered completely from quadriplegia and mutism. In the second patient the only permanent sequellae were slight dysarthria and mild spasticity. Since patients may recover nearly completely from a locked-in syndrome, aggressive supportive therapy seems justified during the initial weeks or months.     

Antral and esophageal rimple: A normal variation

The occurrence of fine antral and esophageal rimpling appears to be the result of contractions of the muscularis mucosa. The lack of persistence during distention is compatible with this conclusion. The folds have no pathologic significance.     

Serum MIP-1α and IL-8 in septic patients

We studied blood MIP-1 and IL-8 in 38 septic patients and 5 healthy volunteers. Both chemokines were undetectable in the healthy volunteers. In sepsis, serum MIP-1 was detected in 45% of the patients and IL-8 in 84%. The levels of MIP-1, but not of IL-8, correlated with CRP, IL-6 and TNF levels. Complication, including various organ failures and mortality, showed no correlation with serum MIP-1 levels. In contrast, we found increased levels of serum IL-8 in septic patients with disseminated intravascular coagulation, central nervous system (CNS) dysfunction or renal failure, and the mortality rate was higher in the IL-8-detectable group than in the IL-8 undetectable group (50% vs 0%,p<0.05). In conclusion, the production of both MIP-1 and IL-8 was increased and initially detectable levels of circulating IL-8 predicted high mortality in sepsis.Objective To determine the significance of the C-C chemokine MIP-1 and the C-X-C chemokine IL-8 in sepsis.Design Prospective study.Setting Clinical investigation, emergency department and general intensive care unit of university hospital.Patients and participants 38 septic patients and 5 healthy volunteers were studied. Sepsis was diagnosed following the criteria formulated by ACCP/SCCM.Interventions 10–20 ml of blood was drawn from each patient at the time of initial diagnosis of sepsis.Measurements and results MIP-1 and IL-8 were determined by sand-wich ELISA. Both chemokines were undetectable in the healthy volunteers. In sepsis, serum MIP-1 was detected in 45% of the patients and IL-8 was detected in 84%. The levels of MIP-1, but not of IL-8, correlated with CRP, IL-6 and TNF levels. Complications, including various organ failures and mortality, showed no correlation with serum MIP-1 levels. In contrast, we found increased levels of serum IL-8 in patients with disseminated intravascular coagulation (DIC) (p<0.05), central nervous system (CNS) dysfunction (p<0.05), renal failure (p<0.01) and the mortality rates were higher in the IL-8 detectable group than in the IL-8 undetectable group (50% vs 0%,p<0.05).Conclusions The production of MIP-1 and IL-8 was increased in sepsis. Furthermore, an initially detectable level of circulating IL-8, but not MIP-1, predicted a high mortality in sepsis diagnosed according to the ACCP/SCCM criteria.This study was supported in part by a Grant-in-Aid from the Japanese Ministry of Education, Science and Culture, the Waxman Institute Research Fund and the Keio Fukuzawa Fund     

Dilemma of an inverted cecal diverticulum simulating a pedunculated polyp: CT appearance

The computed tomographic (CT) appearance of an intussuscepting cecal diverticulum is described. Some features on CT suggest that the term inverted may not be accurate.     

Promising immunotherapies with Th1-related cytokines against infectious diseases

In recent years, there has been an increase in the number of individuals with compromised immune systems. This is due to the rise in the numbers of aging people, patients receiving immunosuppressive treatment after organ transplantation, patients with hematological malignancies, and patients with AIDS. These individuals frequently fall into helper T cell (Th)1–Th2 cytokine imbalance due to a shift towards a Th2-dominant condition. Such a pathological condition puts them at a high risk for developing infectious diseases caused by a variety of microbial pathogens which are often refractory to conventional chemotherapy. Therefore, the administration of Th1-related cytokines is expected to be promising immunotherapy against these intractable infectious diseases. In a series of investigations, we have demonstrated the effectiveness of treatment with Th1-related cytokines, such as interferon (IFN)-, interleukin (IL)-12, and IL-18, in protecting animals from experimental infectious diseases caused by Mycobacterium tuberculosis and Cryptococcus neoformans. Recently, several investigators reported successful clinical treatment with IFN- or IL-12 in patients with intractable tuberculous and nontuberculous mycobacteriosis. Thus, now is an appropriate time for scientific evaluation to clinically confirm the effectiveness of these novel immunotherapies.     

Plaidoyer pour la tisane médicinale

Résumé: La tisane nest pas uniquement un apport deau. Il sagit dune préparation médicinale utile en médecine et en phytothérapie. Elle doit obéir à certains critères pour être de qualité : qualité de la plante, temps dinfusion, conditions dutilisation, correction du goût. La teneur en principe actif est variable, mais elle est effective, quoiquelle dépende de plusieurs facteurs qui en déterminent lefficacité. Des exemples de tisanes pour la pédiatrie sont donnés.     

Pretreatment with peroxysome proliferator-activated receptor α agonist fenofibrate protects endothelium in rabbit Escherichia coli endotoxin-induced shock

Objective To investigate the effects of fenofibrate, an activator of peroxysome proliferator activated receptor (PPAR) , on vascular endothelium and on hemostasis in a rabbit endotoxic shock model.Design and setting Prospective laboratory study in a university laboratory.Subjects 36 male New Zealand rabbits weighing 2.5–3 kg.Interventions We determined in vitro vascular reactivity, endothelium CD31–platelet/endothelial cell adhesion molecule (PECAM) 1 immunohistochemistry, plasma coagulation factors, and monocyte tissue factor expression 5 days after onset of endotoxic shock (0.5 mg/kg intravenous bolus, Escherichia coli lipopolysaccharide) with or without treatment by fenofibrate (mixed in the chow at a concentration of 0.5%) for 15 days before lipopolysaccharide injection and 5 days afterward.Measurements and results Metabolic acidosis and coagulation activation confirmed presence of shock. Fenofibrate decreased monocyte tissue factor expression. It improved endothelial-dependent relaxation at 5 days (Emax=68.2±3.3%, vs. 44.2±2.5% in the non-treated group). Endotoxin-induced deendothelialization was significantly decreased by fenofibrate at 5 days (8.5±1.3% vs. 19.2±3.1% in the nontreated group).Conclusions These data indicate for the first time that fenofibrate, an activator of PPAR-, inhibits monocyte tissue factor expression and protects against endothelial dysfunction and histological injury in endotoxin-induced shock.     

Rapidly progressive dysphagia caused by Forestier’s disease: a case report

Summary Forestiers disease is a systemic rheumatologic abnormality of unknown etiology, characterized by a flowing ossification of the anterior ligament of the spine. In this case study we report on an atypical appearance of Forestiers disease in a 72-year-old woman. This patient had a one-month history of rapidly progressing dysphonia and dyspnea and at the time of admission was unable to eat. She had been operated for gastric and colon carcinoma seventeen months earlier. Total body CT scans showed a flowing ossification of the anterior ligament between levels C2 and C7 and an osteophyte protruding in the ventral direction at level C2. Before the osteophytes removal, a tumor screening was conducted to exclude the presence of distant metastases or occult malignancy. Resection of the large osteophyte was performed via a typical ventral-cervical approach with horizontal skin incision. Six months after the procedure, the patient experienced distinct improvement of her condition and was able to eat both pulpy and solid foods again. In this case example, a rapidly progressive dysphagia was not caused by secondary malignancy, as initially speculated, but resulted from a ventral-cervical osteophyte, considered a rare cause for acute development of severe dysphagia. Early diagnosis of Forestiers disease in this patient led to immediate surgical intervention, which proved to be adequate treatment and enabled the patient to make a good recovery.

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Rasch progrediente Dysphagie durch Morbus Forestier: ein Fallbericht

Zusammenfassung Der Morbus Forestier ist eine rheumatologische Systemerkrankung unbekannter Ätiologie, welche durch eine langstreckige Verkalkung des vorderen Längsbandes der Wirbelsäule gekennzeichnet ist. Im Folgenden wird eine atypische Manifestation des Morbus Forestier in einer 72-jährigen Patientin beschrieben. Die Patientin wurde bei seit einem Monat bestehender Dysphonie, Dyspnoe und völliger Unfähigkeit zu schlucken stationär aufgenommen. Siebzehn Monate zuvor wurde die Patientin an einem Magen- und Kolonkarzinom operiert. Das durchgeführte Ganzkörper-CT zeigte eine ausgedehnte Verkalkung des vorderen Längsbandes von C2–C7 mit einem nach ventral ragenden Osteophyten auf Höhe C2. Vor dessen chirurgischer Entfernung wurden mittels eines Tumorscreenings Fernmetastasen oder Lokalrezidive ausgeschlossen. Die Resektion des prominenten Osteophyten erfolgte über einen typischen ventralen Zugang zur Halswirbelsäule. Sechs Monate nach der Operation konnte die Patientin wieder feste und breiige Nahrung aufnehmen. In diesem Fallbeispiel war die rasch progrediente Dysphagie nicht durch sekundäre Absiedelungen, wie initial vermutet, verursacht, sondern durch einen massiven ventralen zervikalen Osteophyten, welcher an sich selten als Ursache für eine akut progrediente komplette Dysphagie vorkommt. Die frühzeitige Diagnose des Morbus Forestier führte unmittelbar zur operativen Dekompression und erwies sich in diesem Fall als adäquate Behandlung mit guter Remission.

     

Expectations of patients attending a combined headache clinic

Abstract We audited the expectations of patients referred to a combined headache clinic from a specialist headache clinic and a pain relief unit due to the intractable nature of their headache. Our aim was to assess the expectations of definitive diagnosis for the cause of headache, as well as the acceptance of its symptomatic management. We reviewed the notes of all patients referred to the combined clinic over a 2-year period from January 1998 to January 2000. It has been standard practice in the clinic to document patients expectations of definitive diagnosis for the cause of their headache and for its symptomatic treatment. Fifty-two patients (29 women, 23 men; mean age, 40.5 years; range, 15–76 years) were referred to the combined clinic over the two years. These patients had been selected from a total of 460 new patients seen in the specialist headache clinic over this period. All patients had been reviewed by at least one consultant neurologist. Nearly all suffered chronic daily headache of mean duration 8.25 years (range, 1–40 years). Only three patients suffered from migraine as well. Forty patients (77%) were still concerned about the cause of their headaches; 13 (33%) of these wanted further investigations. Fourteen (27%) of the original 52 patients were discharged from the clinic, 9 (17%) were satisfied and accepted symptomatic management of their headache, 5 patients (10%) were unsatisfied and were still looking for a cause for their pain. Five more patients (10%) who demanded further investigations failed to keep follow-up appointments. The remaining 33 patients (64%) accepted symptomatic management within the clinic. One in five patients (20%) attending a tertiary referral clinic for symptomatic treatment of chronic headache did not want symptomatic treatment. They wanted to know the cause of the headache and be provided with a cure. This observation is important when one is assessing outcome measures, because 20% of these patients did not want symptomatic management, the only treatment on offer.     

Shock and the kidney: Pathophysiology and pharmacological support

This article reviews current knowledge as to the physiological mechanisms that control renal vascular resistence. The contribution of both extrinsic and intrinsic neuro-humoral regulation of both blood flow and glomerular filtration rate are described. The changes that occur both to the renal blood flow and glomerular filtration rate in the pathophysiological situation of pre-renal uraemia as well as acute tubular necrosis are described. Within this setting pharmacological manoeuvres that may improve both renal blood flow and glomerular filtration rate are discussed. In addition, the indications for and general principles of haemo- and peritoneal dialysis are described.