Forty-three cases of accessory nerve injury referred to the Peripheral Nerve Injury Unit have been reviewed. Accessory nerve injury results in a characteristic group of symptoms and signs. Referral for treatment is usually delayed, the average time being 11.3 months. Surgical treatment resulted in improvement of symptoms in almost all cases.
Sixty-seven patients were treated with moxalactam in a noncomparative trial of hospitalized patients; 32 had endometritis or chorioamnionitis, 12 had skin and soft tissue infections, 5 had osteomyelitis, 5 had pneumonia, 5 had urinary tract infections, 4 had arthritis, 2 had sepsis from an unknown source, 1 had endocarditis, and 1 had peritonitis. Bacteremia was present in 12 of these patients. Patients were given 3 to 12 g of moxalactam per day (mean, 6.24 g/day) in divided doses every 6 to 8 h. Seven patients were given intramuscular treatment for 3 to 20 days for part or all of their therapy. The rest were given intravenous treatment exclusively. Treatment was continued for 2 to 42 days (mean, 10 days). The dose and the duration of therapy were determined by the type of infection and the response of each patient. There were four treatment failures and one enterococcal-clostridial superinfection. Moxalactam was well tolerated. Allergic reactions led to the discontinuation of the antibiotic in three patients. Prolonged prothrombin and partial thromboplastin times were observed in 2 of 11 patients tested; in both instances in patients had severe underlying diseases, including malnutrition and alcoholism. Pain on intramuscular injection was noted in two patients receiving 1,500 mg, but not in five receiving a lower dose; in one case the pain forced the use of intravenous therapy after one dose, and in the other case the pain was mild and the patient was treated for 20 days. We concluded that moxalactam was effective in the treatment of the types of infections included in this study and produced few adverse reactions.
Studies in the rat have pointed to a role for intercellular adhesion molecule-1 (ICAM-1) in the pathogenesis of acute tubular necrosis. These studies used antibodies, which may have nonspecific effects. We report that renal ICAM-1 mRNA levels and systemic levels of the cytokines IL-1 and TNF-alpha increase 1 h after ischemia/ reperfusion in the mouse. We sought direct proof for a critical role for ICAM-1 in the pathophysiology of ischemic renal failure using mutant mice genetically deficient in ICAM-1. ICAM-1 is undetectable in mutant mice in contrast with normal mice, in which ICAM-1 is prominent in the endothelium of the vasa recta. Mutant mice are protected from acute renal ischemic injury as judged by serum creatinine, renal histology, and animal survival . Renal leukocyte infiltration, quantitated morphologically and by measuring tissue myeloperoxidase, was markedly less in ICAM-1-deficient than control mice. To evaluate whether prevention of neutrophil infiltration could be responsible for the protection observed in the mutant mice, we treated normal mice with antineutrophil serum to reduce absolute neutrophil counts to < 100 cells/mm3. These neutrophil-depleted animals were protected against ischemic renal failure. Anti-1CAm-1 antibody protected normal mice against renal ischemic injury but did not provide additional protection to neutrophil-depleted animals. Thus, ICAM-1 is a key mediator of ischemic acute renal failure likely acting via potentiation of neutrophilendothelial interactions.
155 Background: OKT3 monoclonal antibody therapy results in an acute clinical syndrome (ACS) associated with the release of cytokines such as tumor necrosis factor (TNF) and sequestration of neutrophils in the lungs. We have previously shown that inhibition of TNF does not eliminate OKT3-ACS, suggesting that other factors also contribute to the ACS. We analyzed the mechanisms of complement (C) activation in vivo, during the first hour following OKT3 administration. Methods: Renal transplant (Tx) recipients (n=4) with steroid-resistant rejection and lung Tx recipients (n=4) received OKT3 as treatment for rejection and induction therapy, respectively. Blood samples were obtained in Nafamostat-EDTA tubes. C activation products C4d (classical pathway), Bb (alternative pathway), iC3b (C3 cleavage product) and SC5b-9 (terminal pathway) were measured using ELISA kits (QUIDEL Corporation, San Diego, CA). Hemodynamic parameters were monitored using a Swan-Ganz catheter in lung Tx recipients in the ICU. Neutrophil CD11a, CD11b, and CD18 were monitored in two patients by flow cytometry. Controls included patients receiving 500mg i.v. methylprenisolone (MP) pulses for rejection, adults with acute respiratory distress syndrome who received extracorporeal membrane oxygenation (ECMO) in the ICU and normal individuals. Data were analyzed using the student's t-test and correlated by regression analysis. Results: An increase in the levels of C4d, Bb, iC3b, and SC5b-9 was observed in 7/8 OKT3-treated patients. No significant differences in C activation were found between lung and Table kidney Tx recipients. Total WBC and neutrophil counts at 60 minutes were 65% and 70% of their pre-OKT3 values. A marked increase in the expression of CD11b and CD18 and a decrease of CD11a on neutrophils in parallel with C activation was observed. In lung Tx recipients C4d and iC3b production correlated with increases in central venous pressure (p = 0.023, p = 0.003) and iC3b production correlated with increases in mean pulmonary arterial pressure (p = 0.024). As compared to ECMO (silicone membrane), OKT3 induced activation of C occurred predominantly by the classical pathway, whereas ECMO activated C by the alternative pathway and MP pulses did not activate C.TableConclusions: C activation is an early event after OKT3 administration and is associated with activation of neutrophils and pulmonary hemodynamic changes. In addition to cytokine production, C activation should be studied to delineate potential side-effects of new monoclonal antibodies used in organ transplantation.
The role of platelet-activating factor (PAF) in ischemic acute renal failure was evaluated by administering an oral PAF antagonist (Ro-24-4736) to rats prior to or after interruption of blood flow to both kidneys for 30 min. In animals treated with the PAF antagonist prior to ischemia, renal function was less impaired and histological abnormalities was less pronounced when compared with postischemic kidneys from vehicle-treated animals. Serum creatinine (mg/ dl) 24 h following renal ischemia was 1.58 +/- 0.17 in the PAF antagonist-treated rats compared with 2.19 +/- 0.15 in rats given placebo (P < 0.01). There was less necrosis in the outer medulla of kidneys of PAF antagonist-treated animals (P < 0.01). Tissue myeloperoxidase activity at 48 and 72 h postischemia was lower in kidneys of PAF antagonist-treated rats (P < 0.05). The PAF antagonist was also protective when administered 30 min but not 2 h following the ischemic insult. The coincident use of anti-intercellular adhesion molecule-1 monoclonal antibody did not confer additional protection over that observed with the oral PAF antagonist alone. These data suggest that PAF contributes to the pathophysiology of renal ischemic injury, perhaps by its effects on leukocyte-endothelial interactions. An orally active PAF antagonist can protect against the development of ischemic acute renal failure.
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