Five-year follow-up of hepatitis C-naïve heart transplant recipients who received hepatitis C-positive donor hearts.

BACKGROUND: Due to the risk of transmission of hepatitis C virus, the use of hepatitis C seropositive donors in heart transplantation is controversial. The transmission rate of hepatitis C in this patient population is estimated to range from 67% to 80%. Long-term clinical outcomes of heart transplant recipients of hepatitis C-positive donor hearts are not well described. We report the 5-year long-term outcome of seven hepatitis C-naïve heart transplant recipients who received hepatitis C-positive donor hearts. METHODS: Retrospective analysis of clinical course, liver biochemistry, serology, and hepatitis C virology data. RESULTS: Seven hearts transplant recipients, six men and one woman were included in our study. After a mean follow-up of 63.3 +/- 20.4 months (range 28.2 to 85.9), four of seven (57.1%) patients are hepatitis C-negative, have normal liver function tests, and no clinical evidence of hepatitis. Three of seven (43%) have been diagnosed with hepatitis C by liver biopsy or the HCV-RNA reverse transcriptase polymerase chain reaction at a mean follow-up of 35.1 months (18.8 months posttransplantation). One had an accelerated course of hepatitis that was ultimately fatal, one was successfully treated with interferon, and the third died from other causes than liver injury. Overall, the 5-year survival was 71.4%. CONCLUSIONS: The 5-year survival of hepatitis C-naïve recipients of hearts from hepatitis C-positive donors is similar to heart transplant recipients with hepatitis-negative donor hearts. Nevertheless, the transmission rate is high and hepatitis C infection in this population can lead to considerable morbidity and accelerated, fatal hepatitis.

Molecular epidemiology of a nosocomial outbreak due to Enterobacter cloacae and Enterobacter agglomerans in Campinas, São Paulo, Brazil.

A total of 73 isolates (57 Enterobacter cloacae and 16 Enterobacter agglomerans), recovered during an outbreak of bacteremia in the Campinas area, São Paulo, Brazil, were studied. Of these isolates, 61 were from parenteral nutrition solutions, 9 from blood cultures, 2 from a sealed bottle of parenteral nutrition solution, and one was of unknown origin. Of the 57 E. cloacae isolates, 54 were biotype 26, two were biotype 66 and one was non-typable. Of 39 E. cloacae isolates submitted to ribotyping, 87.2% showed the same banding pattern after cleavage with EcoRI and BamHI. No important differences were observed in the antimicrobial susceptibility patterns among E. cloacae isolates exhibiting the same biotype, serotype and ribotype. All E. agglomerans isolates, irrespective of their origin, showed same patterns when cleaved with EcoRI and BamHI. The results of this investigation suggest an intrinsic contamination of parenteral nutrition solutions and incriminate these products as a vehicle of infection in this outbreak.

Plasmapheresis with intravenous immunoglobulin G is effective in patients with elevated panel reactive antibody prior to cardiac transplantation.

BACKGROUND: Patients with a PRA >10% are considered to be at greater risk for the development of not only acute cellular and humoral rejection but also increased mortality when compared to nonsensitized patients following transplantation. All patients with a PRA >10% at our institution are treated with plasmapheresis and intravenous immunoglobulin G immediately prior to cardiac transplantation. METHODS: Sixteen (Group 1) of 118 patients awaiting cardiac transplantation were found to be sensitized. These patients underwent plasmapheresis followed by 20 gm of intravenous immunoglobulin G (IVIG) immediately prior to cardiac transplantation. Group 1 was compared to the remaining 102 patients with a PRA <10% (Group 2). RESULTS: Despite more patients in Group 1 having a positive crossmatch, pulmonary hypertension, and requiring mechanical circulatory support, there was no statistically significant difference in length of stay or mortality at a mean follow-up of 21.6+/-15.0 months. There was no difference in the occurrence of mild, moderate or severe cellular rejection or humoral rejection in these sensitized patients when compared to Group 2. CONCLUSIONS: Pretransplant plasmapheresis followed by intravenous immunoglobulin G may be an effective therapy that obviates the need for a prospective crossmatch and allows sensitized patients to undergo cardiac transplantation. There is no increase in the post transplant length of stay, occurrence of rejection or short term mortality. Long term follow up is necessary to evaluate whether there is a difference in the development of late rejection, transplant vasculopathy and survival.

Inflammatory myocardial diseases and cardiomyopathies.

Inflammatory myocardial disease has been associated with a variety of infectious and noninfectious etiologies. It is associated with the development of dilated cardiomyopathy in some patients. Given its imprecise diagnosis, varied clinical presentation and undefined natural history, it is quite difficult to make broad generalizations regarding its evaluation and treatment. It is hoped continued application of new molecular biological and other techniques will shed further light on the pathophysiologic mechanisms of myocarditis in humans, thus pointing to therapeutic interventions.

Chemical characterization of the PM10 fraction of airborne particulate matter in the urban atmosphere.

This study examines the chemical composition of PM10, the thoracic fraction of atmospheric particulate matter. This fraction is characterized by a very complex composition and is able to penetrate the human organism corresponding to a "cut point" at the level of the larynx. We used a sampling device to separate the PM10 from other fractions with different aerodynamic behavior. The high volume sampler collected large amounts of material, making it easier to study the micropollutants. Furthermore, it met EPA performance specifications for the measurement of suspended PM10 fraction. We collected the samples during different metereological conditions in the urban area of the town of Leghorn in Tuscany, Italy. Two sites, characterized by different settings, were chosen in the city. Both sites were marked by intense motor vehicle traffic. A better chemical characterization of the collected material became possible using different analytical techniques. The use of large-size cellulose or glass fiber filters allowed us to subdivide the sample and to submit each portion to a different investigative technique. The PAH content of the PM10 fraction was examined, particularly for those compounds of toxicological interest. The concentrations of the compounds were evaluated by HPLC with diode array UV detection. We further determined the contents of various heavy metals from anthropic or telluric sources (Pb, Cu, Fe, Cr, Cd, Mn, V, and Ni) by means of an HGA Graphite Furnace AAS-Zeeman-Effect technique or AA-Flame spectrophotometry. The results of our experiment show that motor vehicle traffic is the prevailing pollution source. The metereological conditions also play a significant role. The samples taken closer to the industrial area of the town showed a slightly higher mean content of PM10 fraction. The concentrations of both heavy metals and PM10 were lower compared with equivalent data from other European cities.

An epidemiological study of the clinical impact of pharmacokinetic anticonvulsant drug interactions based on serum drug level analysis.

The impact of pharmacokinetic anticonvulsant drug interactions on prescribing patterns and serum drug level distribution in a routine clinical setting was evaluated in a population of 848 patients chronically treated with phenytoin, phenobarbital, carbamazepine and valproic acid (either alone or as two-drug combinations) and referred for therapeutic drug monitoring for the first time. While dosages of each drug did not differ significantly between monotherapy and polytherapy patients, significant differences in serum level distribution were found. The proportion of patients with suboptimal serum carbamazepine and valproic acid levels (less than 4 and less than 50 micrograms/ml, respectively) was much greater in the polytherapy than in the monotherapy groups, probably as a consequence of induction of carbamazepine and valproic acid metabolism by combined anticonvulsants. Conversely, the proportion of phenobarbital levels above the upper limit of the optimal range (40 micrograms/ml) was greater among patients receiving phenytoin in combination than among patients taking phenobarbital alone, presumably as a result of phenytoin-induced inhibition of barbiturate metabolism. The therapeutic implications of these findings are discussed.

Carbamazepine-viloxazine interaction in patients with epilepsy.

In six depressed epileptic patients stabilised on carbamazepine therapy, addition of the antidepressant agent viloxazine (300 mg/day for three weeks) induced a marked (average 55%) increase in steady-state plasma carbamazepine concentration. The concentration of the active metabolite carbamazepine-10,11-epoxide also increased during viloxazine therapy, but to a lesser extent (16%). In three patients, these effects were associated with symptoms of carbamazepine intoxication, which regressed rapidly when plasma carbamazepine and carbamazepine-10,11-epoxide levels returned to baseline values after discontinuation of viloxazine. In a seventh patient, viloxazine had to be discontinued after only two weeks because of severe side effects associated with a striking elevation of carbamazepine and carbamazepine 10,11-epoxide levels (by 197% and 137% respectively). Although viloxazine appears to be one of the few antidepressants which can be used safely in patients with epilepsy these results indicate that the drug should be prescribed with great caution in subjects treated with carbamazepine. The mechanism of the interaction probably involves inhibition of the metabolism of both carbamazepine and its active epoxide metabolite.

Pharmacokinetics of the antidepressant drug viloxazine in normal subjects and in epileptic patients receiving chronic anticonvulsant treatment.

In order to evaluate the influence of chronic antiepileptic drug treatment on the kinetics of the antidepressant viloxazine (VLX), six drug-free control subjects and six epileptic patients treated with one or two anticonvulsants (phenobarbital, carbamazepine or phenytoin) were given a single oral dose of VLX (200 mg). On a separate occasion, the patients were also given 200 mg VLX by IV infusion. Plasma VLX levels were determined by GLC. Following oral dosing, VLX was rapidly absorbed from the gastrointestinal tract (peak levels at 0.5-4 h); plasma level profiles showed a considerable interindividual variability but did not differ significantly between patients and controls. Terminal half-lives were 4.3 +/- 1.5 h in the patients and 4.3 +/- 1.8 h in the controls. Clearance and volume of distribution calculated after IV dosing in the patients were 124 +/- 11 ml h-1 kg-1 and 0.73 +/- 0.28 l/kg, respectively. The absolute oral availability was 85 +/- 14%. At variance with findings reported for other antidepressants, VLX kinetics do not appear to be significantly altered by concurrent treatment with enzyme-inducing antiepileptic drugs.

The childbearing center: an alternative birth setting.

A number of reports have noted the trend toward home deliveries. With the aim of providing an alternative to unattended home delivery, an out-of-hospital unit for women at low medical risk was opened in New York City in October 1975. Physical care is provided by a team of nurse-midwives, obstetricians, pediatricians, and ancillary health personnel. Childbirth education is an integral part of the program. Women are carefully screened both initially and during the course of pregnancy, and transfers are made to hospital services when required. In the first 31 months of the program, 244 births were managed in the unit. No life-threatening emergencies have occurred. Experience to date indicates that a unit of this kind can safely offer care to a low-risk obstetric population.