[Cerebral dural arteriovenous fistulas]. / Zerebrale durale arteriovenöse Fisteln.

CLINICAL ISSUE: The cerebral dural arteriovenous (AV) fistula is a rare cerebral vascular malformation. Clinical presentation varies from asymptomatic to acute intracranial bleeding. Classification is based on the venous drainage with a risk assessment of bleeding. The carotid-cavernous fistula is a subtype with its own classification and treatment approaches. PRACTICAL RECOMMENDATIONS: Nowadays, dural fistulas can be diagnosed using high-resolution and time-resolved tomographic methods. Catheter angiography with subsequent interdisciplinary discussion should be performed for precise classification and therapy planning. Both endovascular and surgical treatment methods are available.

Immunologic responses to pneumonia.

Pneumonia in the critically ill surgical patient often results from the bombardment of a previously normal pulmonary system with therapeutic foreign bodies, hospital pathogens, and impairment of the host defenses. Despite its long history as a significant clinical problem, a woefully inadequate amount of study has been directed toward therapy. We created an experimental model of a differential pulmonary infection using a strain of Klebsiella pneumoniae. We then compared the progressively affected pneumonic process versus the normal parenchyma. We measured neutrophil and monocyte complement antibody receptor expression and monocyte and macrophage class II major histocompatibility antigens (HLA-DR) via percent of cells and mean fluorescent intensity outcomes from flow cytometry. The main difference between infected versus noninfected tissues was monocyte DR expression, which was consistently depressed in cells from infected parenchyma. What follows is a discussion of the implications of this work as well as other work in the immunology of pneumonia and cytokine expression. Possible therapeutic modalities are included.

Immunologic responses to pneumonia.

Pneumonia in the critically ill surgical patient often results from the bombardment of a previously normal pulmonary system with therapeutic foreign bodies, hospital pathogens, and impairment of the host defenses. Despite its long history as a significant clinical problem, a woefully inadequate amount of study has been directed toward therapy. We created an experimental model of a differential pulmonary infection using a strain of Klebsiella pneumoniae. We then compared the progressively affected pneumonic process versus the normal parenchyma. We measured neutrophil and monocyte complement antibody receptor expression and monocyte and macrophage class II major histocompatibility antigens (HLA-DR) via percent of cells and mean fluorescent intensity outcomes from flow cytometry. The main difference between infected versus noninfected tissues was monocyte DR expression, which was consistently depressed in cells from infected parenchyma. What follows is a discussion of the implications of this work as well as other work in the immunology of pneumonia and cytokine expression. Possible therapeutic modalities are included.

Role of tumor necrosis factor-alpha in small intestinal microcirculation.

The systemic manifestations of sepsis are associated with increased cardiac output, peripheral vasodilatation, and mesenteric vasoconstriction. Our objective was to determine whether tumor necrosis factor (TNF)-alpha regulates small intestinal microcirculatory changes observed during sepsis. An intact loop of terminal ileum of an anesthetized rat was exteriorized into modified Krebs solution and then topically suffused with varying concentrations of TNF-alpha (10(-4) ng/ml to 10(2) ng/ml), norepinephrine (10(-4) M), and sodium nitroprusside (10(-5) M). Videomicroscopy was used to measure arteriolar (A1, A2, A3) and venular (V1, V2) diameter changes in response to topical TNF-alpha. First order vessel diameters did not change in response to TNF-alpha. However, second and third order arterioles dilated maximally by 35 +/- 16 and 52 +/- 12 per cent, respectively, in a dose dependent manner in response to TNF-alpha. Higher order vessels were more sensitive to TNF-alpha than lower order vessels. Norepinephrine (10(-4) M) produced vasoconstriction in all vessels tested (A2 18 +/- 3 per cent, p < 0.05; A3 6 +/- 6 per cent; V2 13 +/- 4 per cent, p < 0.05). Topical TNF-alpha caused dilation in preconstricted vessels as in the nonpreconstricted vessels. TNF-alpha induced vasodilation was prolonged and not reversed by removal of TNF-alpha. These data demonstrate statistically significant dilation in response to TNF-alpha in second and third order arterioles and venules of the small intestine. Persistent vasodilation suggests an induced mechanism of vasodilation in response to TNF-alpha that remains active even after removal of exogenous TNF-alpha. We, therefore, conclude that TNF-alpha causes persistent vasodilatation beyond the period of actual exposure to TNF-alpha in the small intestinal microcirculation. This effect is not altered by the presence of norepinephrine. These data suggest that small intestinal vasoconstriction observed during clinical conditions such as sepsis is unlikely to be mediated by TNF-alpha.

Hemorrhagic shock-induced alterations in circulating and bronchoalveolar macrophage nitric oxide production.

Local and systemic host immune functions are markedly altered after trauma. Activated macrophages (M phi) are the major effector cells of protective immunity, mediated in part by nitric oxide (NO). This study was undertaken to determine the effects of hemorrhage (HEM) on M phi cytotoxic function as measured by NO production. Male Sprague-Dawley 350- to 400-g rats were studied. Sham animals only had their carotid artery exposed and ligated. Hemorrhaged animals had carotid artery cannulation followed by HEM to SBP of 40 mmHg, sustained for 45 min, followed by resuscitation with shed blood and crystalloid. Recovered animals were sacrificed (n = 5 each) at 6, 12, 24, and 72 hr after HEM; blood and alveolar M phi were then isolated and examined. A monolayer of adherent M phi was examined for NO production in resting state and after in vitro LPS stimulation. (1) HEM resulted in significantly reduced alveolar M phi yield at 12 and 24 hr. (2) HEM increased NO production by circulating M phi at 24 hr (P < 0.05), while alveolar M phi had significantly increased NO production at all time points after HEM (P < 0.05). (3) LPS stimulation significantly increased NO production in both circulating and alveolar M phi in sham animals and 6 hr after HEM but not at any other times. We therefore conclude that HEM causes early and prolonged activation of NO production by alveolar M phi and delayed and brief activation of circulating M phi. Alveolar and circulating M phi are unable to significantly increase NO production in response to LPS stimulation during the later phases of HEM.(ABSTRACT TRUNCATED AT 250 WORDS)

Hepatic cryotherapy for liver tumors. Development and clinical evaluation of a high-efficiency insulated multineedle probe system for open and laparoscopic use.

A high-efficiency hepatic cryosurgical unit has been developed and evaluated. It is capable of simultaneously driving three implantable insulated cryoneedle probes. The system has been used to treat 18 patients with secondary and 4 patients with primary liver cancer: open (n = 12), total laparoscopic (n = 6), laparoscopic assisted (n = 4). In three patient laparoscopic cryotherapy was repeated inside 6 months. Intraoperative bleeding was encountered in three patients undergoing high-volume hepatic freezing but the bleeding was easily controlled. A fall in the core body temperature was encountered in 10 out of 22 patients and averaged 0.4 degree C. There was one postoperative death from liver failure in an 80-year-old patient in whom a large hepatoma was frozen. The most consistent postoperative biochemical change was hyperbilirubinaemia (n = 3). A right-sided pleural effusion developed in two patients after freezing of lesions on the superior surface of the right lobe. A survival benefit was encountered in three patients, one with central cholangiocarcinoma and the other two with large solitary secondary deposits (melanoma, colon cancer). Seven patients with multiple metastases and two patients with large hepatomas developed recurrence at the frozen site or elsewhere in the liver inside 12 months of follow-up and no clinical benefit could be demonstrated by cryotherapy in this group. In nine patients, the follow-up has been too short (< 18 months) to permit any conclusion on outcome. The current limitations of hepatic cryotherapy are largely due to incomplete tumor destruction.(ABSTRACT TRUNCATED AT 250 WORDS)

Second place winner of the Conrad Jobst Award in the gold medal paper competition. Increased antibiotic effectiveness in a model of surgical infection through continuous infusion.

As long as infection remains the most common cause of morbidity and mortality in severely ill patients, there exists the need for more effective anti-infective therapy. The current study was undertaken to determine whether continuous infusion (CONT) is superior to intermittent administration (INT) of an equal amount of cefazolin (CEF) in a model of surgical infection. The thigh suture model consists of the surgical placement of 1 cm of cotton suture with absorbed K. pneumoniae into the thigh muscle of mice. The experimental groups were: 1) controls (n = 20) with thigh suture inoculation and treatment with intraperitoneal (IP) sterile saline; 2) CONT infusion group that received CEF at 60 mg/kg IP 30 minutes before inoculation followed by CONT IP infusion at 180 mg/kg/day (n = 22) for 3 days; and 3) INT injection group that received CEF at 60 mg/kg IP 30 minutes before inoculation followed by INT IP injections every 8 hours at 180 mg/kg/day (n = 20) for 3 days. All CEF treated animals received identical quantities of total CEF, and all groups were followed for 10 days. The control and INT CEF groups had 20% survival, whereas the CONT CEF group had 81% survival, (P < 0.001). Continuous CEF yielded constant serum levels of 19 +/- 1 micrograms/mL, whereas INT injections resulted in peak serum level of 74 +/- 12 micrograms/mL at one minute but declined to 3.9 +/- 0.9 micrograms/mL in 2 hours. Although there was statistically significant tissue bacterial growth in the INT injection group, there was extensive tissue bacterial clearance in the CONT infusion group.(ABSTRACT TRUNCATED AT 250 WORDS)

Improved survival in simulated surgical infection with combined cytokine, antibiotic and immunostimulant therapy.

A study was performed to find an ideal combination and sequence of cytokines, antibiotics and immunorestorative agents to enhance survival from serious infection. The effects of combinations of granulocyte-macrophage colony-stimulating factor (GM-CSF), tumour necrosis factor (TNF) alpha, the immune adjuvant muramyl dipeptide (MDP) and two systemic antibiotics were studied in a validated murine model of surgical infection. A single cotton suture containing absorbed Klebsiella pneumoniae was placed into the thighs of mice to produce local and systemic infection. Control mice received a volume of subcutaneous saline equal to that of the therapeutic agent; only 18 per cent survived 9 days after infection. The survival time of mice treated with any single agent was similar to that of controls. The group given maximal combined therapy (65 mice) received GM-CSF, TNF-alpha, MDP, and ampicillin-sulbactam or cefoxitin for 6 days. The survival rate in this group 9 days after the introduction of infection was 84-90 per cent (P < 0.0001), suggesting that specific combinations of cytokines, immunostimulants and antibiotics may be useful in combating lethal infection.

Pneumonia in the surgical intensive care unit. Immunologic keys to the silent epidemic.

OBJECTIVE: The authors undertook a prospective study of trauma victims in the intensive care unit (ICU) to investigate the clinical course of pneumonia and the local and systemic immune responses to the pneumonia. SUMMARY BACKGROUND DATA: The silent epidemic of pneumonia has been an "unappreciated killer" in terms of being overlooked in surgical ICUs for the past 5 years, and specifically, the most common major infection after severe trauma. Little is known about the immune response to an acute pulmonary infection. METHODS: The authors studied 50 consecutive, critically ill trauma patients, with a mean injury severity score of 28 +/- 2, who developed pneumonia while ventilated mechanically. Patients were observed clinically, and specific immunologic parameters, including major histocompatibility antigen HLA-DR, complement receptor (CR3), and Fc receptor (FcRIII), were measured in circulating and local alveolar leukocytes for up to 30 days. Eleven patients provided unique clinical data via bronchoscopy for unilateral pneumonia, with collection of bronchoalveolar lavage (BAL) fluid from both the infected and uninfected sides. RESULTS: Patients developed clinical pneumonia 5.3 +/- 0.4 days after admission to the ICU. At diagnosis, mean temperature was 101.4 F, white blood cell count was 16,000/mm3, arterial oxygen tension was 104 +/- 14, fraction of inspired oxygen was 0.47, and positive end-expiratory pressure was 5. Thirty patients (Group A) recovered relatively promptly; 20 patients had prolonged illnesses (Group B), 15 of whom ultimately survived, and five of whom died. Patients with poor outcomes had greater leukocytosis (p < 0.05) and temperature elevation (p < 0.05) after 5 days of pneumonia. Immunologically, peripheral leukocyte expression of HLA-DR, FcRIII, and CR3 was equivalent in both groups. However, the expression of all three antigens on local alveolar leukocytes was decreased to a greater extent in the poor outcome group compared to the good outcome group, evident before any clinical differentiation between the two outcome groups. CONCLUSIONS: Pneumonia prolonged duration of mechanical ventilation, ICU and hospital stay, and overall infectious morbidity. Although immune suppression has been recognized as a result of initial injury, the development of pneumonia coincided with the nadir of immune function. Poor outcome patients were clinically identifiable 5 days after pneumonia and immunologically identifiable within 2 days. Moreover, there was localized suppression of pulmonary leukocytes at the site of the infiltrate compared to the uninfected lobes. This same alteration was noted in experimental Klebsiella pneumoniae pneumonia. This evidence suggests that there is active immune participation within the respiratory system. It also suggests that there are predispositions to pulmonary infections, and it may allow immune modulation targeted to pulmonary leukocytes to hasten clinical recovery and minimize pulmonary dysfunction.

The contribution of open extremity fractures to infection in multiply injured patients.

We sought to determine whether a contaminated open fracture was a reliable component for calculating the Outcome Predictive Score in patients with multiple injuries. We studied 41 patients whose primary source of contamination was open extremity fractures. Only one of the 41 patients developed osteomyelitis. The rate of infection from an open fracture is minimal in the multiply injured patient. Inclusion of patients with open fractures in studies that assess the likelihood of infection and the value of anti-infective agents incorrectly identified patients for clinical trials and results in an overestimation of survival based on the Outcome Predictive Score. These findings suggest that open fractures should be excluded as an entry criterion in future clinical trials.

Alteration of mononuclear cell immune-associated antigen expression, interleukin-1 expression, and antigen presentation during intra-abdominal infection.

Intact peritoneal macrophage (M phi) function is critical to successful localization of intra-abdominal infection. Peritoneal macrophage antigen presentation capacity (APC), interleukin-1 (IL-1) expression, and immune-associated (Ia) antigen expression and abscess formation were determined following cecal ligation and puncture. APC and IL-1 expression were measured by coculture with a T-helper cell clone and by measuring subsequent proliferation. Ia expression was determined in blood, peritoneal M phi, and splenocytes using anti-Ia monoclonal antibody stain and flow cytometric analysis. Significant reductions in both Ia expression and APC were found 1 and 4 days after CLP with no change in IL-1 expression. Muramyl dipeptide, which enhances M phi phagocytosis, partially abrogated the depression in antigen presentation but did not affect Ia expression. Peritoneal M phi Ia expression and APC, but not IL-1 expression, were depressed after experimental peritonitis. The recovery of M phi function by day 14 coincides with clinical recovery and abscess formation, and restoration of early M phi depression may improve outcome.

Regional and systemic immune responses in a murine model of empyema.

The extent to which circulating leukocytes reflect functional capacity at the site of infection is unclear despite a century of debate. We conducted experiments designed to clarify those relationships as well as the relationship of pleural and peritoneal responses to infection. Empyema was established in inbred CBA/J mice by introducing Escherichia coli and Bacteroides fragilis into the thoracic cavity through a limited thoracotomy. Walled off abscesses appeared seven days after the introduction of infection. Cell surface expression of murine class II major histocompatibility antigen was measured in peripheral leukocytes, thoracic and peritoneal cavity exudate leukocytes and abscess cells for 60 days after the introduction of infection. The peripheral antibody response was determined by measuring immunoglobulin M (IgM) and immunoglobulin G (IgG) specific for the two organisms. The results demonstrated that, after introduction of infection into the thoracic cavity, mice mounted a specific systemic humoral immune response by producing IgM and IgG. There was a pronounced concomitant cellular response in thoracic and peritoneal cavity exudate cells. However, there was no evidence of a systemic cellular response in circulating lymphocytes or monocytes and polymorphonuclear leukocytes measured as a single group. We conclude from these experiments that measurements of peripheral immune parameters may adequately reveal the humoral response to infection, but it does not reflect the local immune cellular response. Furthermore, a special relationship exists between the peritoneal and the thoracic cavities, whereby an inflammatory process in the thoracic cavity leads to a marked activation of inflammatory process in the peritoneal cavity without affecting peripheral circulating cells to the same extent.