The association of circulating endotoxin with the development of the adult respiratory distress syndrome

Despite extensive investigation, the pathogenesis of the adult respiratory distress syndrome (ARDS) remains uncertain. As yet, there is no clear explanation of why some patients at risk for ARDS develop the syndrome, whereas others do not. Neutrophils and complement fragments have been implicated in the acute lung injury, but it is clear from published data that evidence of complement activation alone predicts neither the development nor the severity of ARDS. We investigated whether the combination of endotoxin, a leukocyte-priming agent, and complement fragments, leukocyte-stimulating agents, was associated with the development of ARDS. Ninety-eight patients were identified as being either at risk for the development of ARDS or having ARDS, and serial blood samples were obtained. There was no correlation between C5 fragments and the development of ARDS. C3 fragment levels were increased in 89% of the patients with ARDS, but they were also increased in 62% of patients at risk. Endotoxin was detected in 74% of the plasma samples obtained from patients at risk who subsequent developed ARDS and in 64% of the plasma samples obtained from the patients with ARDS. In contrast, only 22% of the plasma samples obtained from the patients at risk who did not develop ARDS had measurable endotoxin. We suggest that the combination of endotoxin and complement fragments may be one mechanism involved in the development of ARDS.     

Balanced analgesia after hysterectomy: the effect on outcomes.

Balanced analgesia (an opioid and a nonsteroidal anti-inflammatory agent) after hysterectomy often leads to better postoperative pain outcomes. Researchers compared post-hysterectomy patients who received balanced analgesia with those who received only morphine patient-controlled analgesia, and their relationship with pain scores, ambulation, and hospital length of stay.     

New areas for therapeutic intervention in the treatment of rheumatic disease.

Anti-rheumatic therapy has been targeted against the symptoms arising from chronic inflammation of the joint. This has resulted in the extensive use of non-steroidal anti-inflammatory drugs. It is now becoming apparent that these agents have no beneficial effect on disease progression. This mini review concentrates on the formation and maintenance of pannus, the granulomatous tissue responsible for cartilage and bone erosion. This reveals a number of possible therapeutic targets. Protease inhibitors could be used to interfere with the degradatory processes. The diverse functions of endothelial cells suggest oedema formation, cell accumulation and supply of nutrients to the granulomatous tissue could all be targeted by appropriate therapy. Alternatively the immune processes that control pannus formation and state of activation could be regulated by interfering with antigen presentation and the cytokine network.     

Chronic lower extremity ischemia: a human model of ischemic tolerance.

BACKGROUND: Ischemic preconditioning (IPC) has been found in animals to have a protective effect against future ischemic injury to muscle tissue. Such injury is unavoidable during some surgical procedures. To determine whether chronic ischemia in the lower extremities would imitate IPC and reduce ischemic injury during vascular surgery, we designed a controlled clinical study. PATIENTS AND METHODS: Two groups of patients at a university-affiliated medical centre with chronic lower-extremity ischemia served as models of IPC: 6 patients awaiting femoral distal bypass (FDB) and 4 scheduled for aortobifemoral (ABF) bypass grafting for aortoiliac occlusive disease. Seven patients undergoing elective open repair of an infrarenal abdominal aortic aneurysm (AAA) were chosen as non-IPC controls. Three hematologic indicators of skeletal-muscle injury, lactate dehydrogenase (LDH), creatine kinase (CK) and myoglobin, were measured before placement of the proximal clamp, during surgical ischemia, immediately upon reperfusion, 15 minutes after and 1 hour after reperfusion, and during the first, second and third postoperative days. RESULTS: Baseline markers of skeletal-muscle injury were similar in all groups. In postreperfusion samples, concentrations of muscle-injury markers were significantly lower in the 2 PC groups than in the control group. For example, at day 2, LDH levels were increased by about 30% over baseline measures in the elective AAA (control) group, whereas levels in the FDB and ABF groups remained statistically unchanged from baseline. Myoglobin in controls had increased by 977%, but only by 160% in the FDB and 528% in the ABF groups. CK levels, in a similar trend, were 1432% higher in the control group and only 111% (FDB) and 1029% (ABF) in the study groups. Taken together, these data represent a significant level of protection. CONCLUSIONS: Patients with chronic lower-extremity ischemia suffered less severe ischemic injury after a period of acute ischemia than those with acute ischemia alone. Ischemic preconditioning is one proposed mechanism to help explain this protective effect.     

Kidney Transplantation in Patients with Antibodies against Donor HLA Class II

The immunologic risk associated with donor-specific antibodies (DSA) against Class II human leukocyte antigens (HLA) in kidney transplant (KTx) recipients is unclear. The aim of this study was to determine the outcome of KTx when DSA was detected only against HLA Class II. To isolate the impact of anti-Class II DSA, we retrospectively analyzed 12 KTx recipients who at baseline had a positive B-cell flow cytometric crossmatch (FXM) and a negative T-cell FXM. Using alloantibody specification analysis, 58.3% (7/12) had DSA against donor Class II and 41.7% had no demonstrable DSA. Biopsy-proven AMR occurred in 57% (4/7) in the Class II(+) group and 0% in the Class II(-) group (p > 0.05). Peritubular capillaries stained positive for C4d in 86% (6/7) of the Class II(+) patients and in 40% (2/5) of the Class II(-) patients (p > 0.05). One patient in the Class II(+) group lost their graft at 3 months to accelerated transplant glomerulopathy, while all other grafts were functioning 3-37 months posttransplant despite the persistence of anti-Class II DSA. We conclude that KTx recipients with clearly defined anti-Class II DSA are at risk for humoral rejection suggesting that desensitization and/or close posttransplant monitoring may be needed to prevent AMR.