Sirolimus and mycophenolate mofetil as calcineurin inhibitor-free immunosuppression in a cardiac transplant patient with chronic renal failure.

Chronic renal failure triggered by calcineurin inhibitor (CNI)-based immunosuppression is a common complication after cardiac transplantation. Sirolimus and mycophenolate mofetil (MMF) are 2 newer immunosuppressive agents with no documented nephrotoxic side effects. This case report describes a patient with ongoing chronic renal failure 10 months after cardiac transplantation on cyclosporine-based immunosuppressive therapy. Conversion of the immunosuppressive regimen from cyclosporine to sirolimus and MMF resulted in freedom from acute rejection, excellent cardiac graft function and consistently improved renal function. This case illustrates the beneficial potential of sirolimus and MMF as CNI-free and safe long-term immunosuppression in a patient with chronic renal failure after heart transplantation.     

Percutaneous transluminal coronary angioplasty in a patient with paroxysmal nocturnal hemoglobinuria

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired chronic hemolytic anemia associated with an unusual susceptibility to hemolytic crisis, infection, and venous thrombosis which would be aggravated by a number of factors including surgery. We report a case of PNH undergoing percutaneous transluminal coronary angioplasty and discuss the corresponding perioperative management.     

Rotational ablation of coronary artery lesions using single,large burrs

Previous clinical use of the Rotablator^(TM) In coronary artery disease has involved a sequential increase in burr sizes up to 2 mm in diameter and has often utilized balloon adjunct to achieve an optimal result. We report our experience and describe our technique using a single, large burr (2.25, 2.5, or 2.75 mm diameter) without balloon assistance. The burr size was selected to approximate 70–90 percent of the apparent normal lumen diameter. Thirty-one patients with 36 lesions of complex morphology (eccentric, irregular, calcified, ulcerated, at bends, at bifurcations, completely occluded, as well as balloon failures) were successfully treated with the Rotablator^(TM). Results were assessed by computerized quantitative angiography. The percent diameter stenosis (mean ± SD) for the group was reduced from 69.8 ± 11.3% to 30.9 ± 10% (p < 0.001). The mean absolute diameter stenosis increased from 0.9 ± 0.3 mm to 2.2 ± 0.3 mm (p < 0.001). Angiographically visible dissections were seen in 4 patients and were uncomplicated in 2. One patient had a non-Q-wave myocardial infarction. A fourth patient had a presumed acute occlusion 36 hr after the procedure, necessitating emergency bypass surgery, but without Q waves on the electrocardiogram or wall-motion abnormalities on the echocar-diogram. Nitroglycerin was infused through the Rotablator^(TM) catheter and has considerably lowered the degree and frequency of spasm. No other acute complications occurred. The mean procedure time using a single burr was shorter than when multiple burrs were used: 56.5 vs. 97.3 min, respectively (p < 0.05). The use of a single, large-size Rotablator^(TM) burr is an effective method of treating complex coronary stenoses without balloon assistance and has an encouragingly low complication rate and short procedure time. © 1992 Wiley-Liss, Inc.     

Infantile autism—fragile X: Molecular findings support genetic heterogeneity

Twenty-two members of 18 families with autism have been examined for the presence of mutations and abnormal methylation in the FMR-1 region at Xq27.3. All patients fulfilled diagnostic criteria of infantile autism. A characteristic pattern of insertion and methylation were detected after Southern blot analysis in 7 autistic individuals expressing the fragile site at Xq27.3. Normal DNA patterns were observed in 15 autistic boys cytogenetically negative for the fragile site. The results indicate a lack of involvement of the FMR-1 region in infantile autists negative for fragile X expression. © 1992 Wiley-Liss, Inc.     

A likelihood approach to HLA serology.

A likelihood approach to HLA serology has been developed in which the aim is not to define a recognition set for a serum but to describe the serum's ability to react with each and every antigen in the test cells, this ability being quantified in terms of the probability of a positive reaction. For a given set of probabilities, one for each antigen, it is possible to derive the probability of the observed set of reactions (the likelihood of the set of probabilities). The maximum possible value of the likelihood for any possible combination of the probability set can then be sought, but this requires a maximization of likelihood with respect to 60-100 independent parameters. Theoretical considerations of the shape of the likelihood surface prove that, in this particular case, this is a feasible proposition. This approach allows the recognition of three groups of antigens: those for which there is considerable evidence of a specificity, those for which there is either no specificity or a very weak specificity, and those for which there is insufficient evidence on which to base a conclusion. The existence of a specificity can be tested using a log likelihood ratio as a statistic, but the usual assumption of a chi 2 distribution of this statistic cannot automatically be made in this situation. Therefore, the distribution is estimated by simulation. A serologist using this approach would receive considerably more information as to the serum's reaction patterns and valid statistics for the existence, or not, of a specificity.     

Piperacillin-Tazobactam Pharmacokinetics in Patients With Intraabdominal Infections

Study Objective . To determine the appropriate compartmental and noncompartmental pharmacokinetic parameters for intravenous piperacillin and tazobactam. Design . Sequential selection of patients entered into a randomized, open-label clinical efficacy trial. Setting . Los Angeles County-University of Southern California Medical Center. Participants . Sequential sample of 18 patients admitted for intraabdominal infections and consented into a comparative antibiotic trial. Interventions . Patients received piperacillin 4 g plus tazobactam 500 mg by intravenous intermittent infusion every 8 hours. Measurements and Main Results . The estimated noncompartmental pharmacokinetic parameters (mean ± SD) for piperacillin and tazobactam, respectively, were as follows: maximum concentration in plasma 218.7 ± 48.9 μg/ml and 27.8 ± 9.1 μg/ml; half-life 1.07 ± 0.22 hours and 1.00 ± 0.27 hours; elimination rate constant 0.67 ± 0.13 hr⁻¹ and 0.73 ± 0.18 hr⁻¹; area under the concentration-time curve from zero hour to infinity 288.5 ± 71.25 mg·hr/L and 36.3 ± 9.55 mg·hr/L; total plasma clearance 14.75 ± 3.93 L/hour and 14.78 ± 4.39 L/hour; renal clearance 5.69 ± 1.94 L/hour and 7.85 ± 3.37 L/hour; volume of distribution at steady state 21.00 ± 4.18 L and 22.47 ± 8.27 L; and mean residence time 1.72 ± 0.29 hours and 1.79 ± 0.35 hours. Conclusion . Our findings were similar to those in other surgical patient models. The two-compartmental model best described piperacillin and tazobactam disposition in our patients. Bayesian analyses of the two-compartment models of piperacillin and tazobactam were able to predict trough, peak, and 2-hour postadministration levels without bias.     

Oral session 1: General neurology

Oral session 1: General neurology     

Effects of prolactin on secretion and synthesis of human chorionic gonadotropin in human term placentas in vitro: short-term increase in secretion, followed by medium-term suppression of synthesis and secretion.

We studied the influence of human prolactin on the secretion and de novo synthesis of human chorionic gonadotropin (hCG) in the human term placenta in culture. Placental tissue from 14 patients with uncomplicated pregnancies and deliveries was prepared mechanically, with addition of a Percoll gradient step. hCG levels were determined in the culture media and in the cytosolic fraction of cells by means of an enzyme immunoassay with coated beads. The amount of newly synthesized hCG was measured by the extent of incorporation of 35S-methionine into the hCG molecule. Our results showed that human prolactin had two different effects in vitro: between 1/2 and 1 h, prolactin slightly increased secretion of hCG into the culture medium without affecting de novo synthesis; after 2 h, prolactin began to cause a significant decrease in both secretion and de novo synthesis of hCG over several hours. It appears that both effects are receptor mediated, for ovine prolactin failed to produce any response. We conclude that prolactin is one of the main factors regulating the synthesis and secretion of hCG in the human trophoblast at term.     

Human spumaretrovirus antibody reactivity in multiple sclerosis

The role of human spumaretrovirus (HSRV) infections in the pathogenesis of multiple sclerosis (MS) was investigated with recombinant HSRV env-specific enzyme-linked immunosorbent assay. The presence of HSRV antibodies was determined in pairs of serum and cerebrospinal fluid (CSF) samples from 60 MS patients. In 7 of these patients serial serum and CSF samples were obtained in relation to the clinical activity of the disease during a period of 2 years. No increased antibody reactivity was demonstrable in the MS population compared with 14 aseptic meningitis patients, 50 blood donors and 16 healthy controls. Slightly elevated levels of antibodies were demonstrable in serum and/or CSF in 4 MS patients but also in 1 patient with aseptic meningitis, 1 blood donor and 1 child. No marked serum or CSF HSRV antibody fluctuation was observed in the MS patients followed longitudinally. Thus, this study does not support the involvement of HSRV in the pathogenesis of MS.