Renal transplant function after ten years of cyclosporine.

Although the nephrotoxic side effects of cyclosporine are well known, the impact of long-term CsA on renal transplant function is uncertain. We studied 5-10-year renal function in 347 CsA-treated patients, and in 64 randomly selected non-CsA-treated patients who had a minimum of 55 months of graft function. Non-CsA patients had a lower creatinine (Cr) level at one year than CsA patients (P = .001), with no change in renal function over time (P = .6). In CsA-treated patients there was also no suggestion of progressive renal damage, as evidenced by no change in Cr or 1/Cr. Simple linear regression models of 1/Cr vs. time for the first 10 years posttransplant were fit to the data for each patient. Analysis of the Y-intercept estimates from these regressions showed that age (P = .001), sex (P = .001), cyclosporine toxicity (P = .024), and initial cyclosporine dosage (P = .016) significantly affected the one-year serum Cr. Variables not affecting one-year Cr included donor source, early rejection episodes, late rejection episodes, ATN, diabetes, transplant number, HLA ABDR mismatch (for cadaver transplants), maximum PRA, and PRA at transplant. Analysis of the slope estimates from the regressions revealed that only age (P = .001) and late rejection episodes (P = .001) significantly affected the rate of change in 1/Cr over time. We conclude that, in long-term renal transplant patients, there is no evidence of progressive deterioration in renal function due to CsA nephrotoxicity.     

Protective capacity of polyclonal and monoclonal antibodies directed against endotoxin during experimental sepsis

Both monoclonal antibody (MAb) and polyclonal antibody (PAb) directed against the shared core/lipid A region of lipopolysaccharide (LPS) (endotoxin) provide protection during experimental gram-negative bacterial sepsis. Although these preparations have not been compared, clinical trials administering either preparation to septic patients have been instituted. The core/lipid A region of LPS represents an antigenic domain common to many, if not all, gram-negative microbes, and thus represents an ideal target site for antibody binding. We sought to determine (1) the protective capacity of similarly reactive IgG anti-core LPS/lipid A MAbs and PAbs, (2) whether the timing of administration was important, and (3) whether either would act additively with antimicrobial agents. Antibody was administered intravenously to outbred mice, and Escherichia coli 0111:B4 was then administered intravenously or intraperitoneally with hemoglobin. Monoclonal antibodies and PAbs were equally protective, and protection was maximized by pretreatment, although the effect extended to four hours after bacterial challenge. Both MAbs and PAbs acted in concert with gentamicin hydrochloride to further reduce lethality. We concluded that MAbs and PAbs were equally protective and that clinical utility may eventually be dictated by ease and cost of antibody production.     

Calciphylaxis – a topical overview

'Calciphylaxis', a calcification syndrome associated with ischaemic cutaneous necrosis, is acquired naturally in humans in disease states. It is a life and limb-threatening complication, usually observed in patients with renal disease and secondary hyperparathyroidism, but known to occur in the absence of renal or parathyroid disease. The reported mortality rate, which ranges from 60-80%, relates to wound infection, sepsis and organ failure. It is a small-vessel vasculopathy, which is estimated to occur in about 4% of haemodialysis patients. Clinically, violaceous, reticulate areas of cutaneous necrosis and eschar may be evident, particularly in the extremities. In addition to the clinical picture, a raised calcium phosphorous product, an elevated parathyroid hormone level, radiographic evidence of vessel and soft-tissue calcification and the finding of mural calcification affecting small arteries and arterioles on histopathology help to confirm the diagnosis of this entity which generally has a poor prognosis. A high index of suspicion and an active multidisciplinary management approach, with rigorous attention to wound care and prevention of sepsis, are vital in the management of these patients. In this overview, we discuss the pathophysiology, clinical features and associations, risk factors, diagnosis and management issues relating to calciphylaxis.     

Status epilepticus in children: etiology, clinical features, and outcome

Between August 1984 and September 1986, data were gathered prospectively on 114 episodes of convulsive status epilepticus, defined as seizure duration longer than 30 minutes, affecting 97 children. Status epilepticus was symptomatic in 72% (chronic 59%, acute 13%) and idiopathic or febrile in 28%. We identified precipitating factors in 63% of episodes. The most common factors were inadequate blood levels of anticonvulsants (32 of 60 episodes in children with prior seizures) and febrile illnesses, excluding meningitis or encephalitis (38 of 114 episodes). There was an elevated peripheral white blood cell count in 60%, acidosis with a pH of less than 7.0 in 12.5%, and cerebrospinal fluid pleocytosis not due to meningitis or encephalitis in 8 of 64 episodes. Eight children died, three with severe pre-existing brain damage, two with meningitis, and two with a poorly defined encephalopathy. Eighteen children developed a new neurologic deficit. Outcome was associated with the etiology and duration of status epilepticus, with age at the time of status a minor factor. A permanent deficit occurred in only five children with idiopathic or febrile status epilepticus.     

Endotoxin promotes synergistic lethality during concurrent Escherichia coli and Candida albicans infection.

Previous studies have suggested that the lipopolysaccharide (LPS, endotoxin) component of the gram-negative bacterial cell wall is a key virulence factor that serves to enhance mortality during infections in which fungi and gram-negative bacteria are copathogens. To test this hypothesis, mice were challenged ip with Escherichia coli 0111:B4, Candida albicans, or both, and the effect of administration of anti-E. coli 0111:B4 LPS monoclonal antibody (mAb) 8G9 on endotoxemia, bacteremia, and mortality was assessed. E. coli (2 x 10(7) colony-forming units (CFU)) plus C. albicans (6 x 10(7) CFU) infection produced 100% mortality at 7 days, compared to the relatively low mortality caused by infection with either E. coli or C. albicans alone (20 and 3%, respectively, P less than 0.01). Administration of mAb 8G9 to animals receiving both pathogens reduced mortality (100% versus 14%, P less than 0.05), endotoxemia (3653 +/- 3187 versus 2 +/- 2 endotoxin units (EU), P less than 0.01), and bacteremia (4.2 +/- 2.3 versus 1.1 +/- 2.1 log(CFU/ml), P less than 0.01) compared to animals receiving saline alone. In a separate series of experiments, purified E. coli 0111:B4 LPS was administered in place of viable E. coli. The simultaneous injection of 200 micrograms E. coli LPS and C. albicans (6 x 10(7) CFU) produced 93% mortality at 7 days, compared to the low mortality that occurred following injection with either E. coli 0111:B4 LPS or C. albicans alone (21 and 3% respectively, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)