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Biomedical subjects

S Kusne

Publications and source records attributed to S Kusne.

At least 73 records · Page 4Linked to original sources

Successful therapy for cerebral phaeohyphomycosis due to Dactylaria gallopava in a liver transplant recipient.

A 68-year-old liver transplant recipient who was being treated with FK 506 and immunosuppressive steroid therapy was admitted to our medical center because of a tonic-clonic seizure. Computed tomography of the head revealed multiple discrete cerebral abscesses, and culture of fluid drained intraoperatively yielded a dematiaceous fungus. The isolate was susceptible to amphotericin B and itraconazole but was resistant to flucytosine and fluconazole. The patient was successfully treated with a prolonged course of amphotericin B colloidal dispersion and itraconazole, as evidenced by both clinical and radiographic resolution of disease over a 2-year follow-up.

Aged↗

Candida carriage in the alimentary tract of liver transplant candidates.

Thirty randomly selected patients with advanced chronic liver disease, which had been evaluated for possible liver transplantation, were sampled endoscopically at 7 alimentary tract locations to assess the frequency and amount of Candida carriage. Eighty-one percent (127/156) of the samples obtained contained Candida and 53% (82/156) yielded high counts (> 300 CFU/ml). The most predominant Candida species isolated at each site was Candida albicans, which accounted for 103 (64%) of the 160 fungal isolates. The other Candida species isolated included C tropicalis 30 (19%), C krusei 16 (10%), and C glabrata 11 (7%). Although the number of sites at which yeast was present and the quantities of yeast at each site varied widely among the patients studied, 100% of the patients had Candida in at least one site of the gastrointestinal tract. Eighty-six percent (24/28) of the duodenal aspirates contained Candida and 50% (14/28) of the duodenal samples contained greater than 300 CFU/ml. A positive culture from the stomach was a reliable predictor of the presence of Candida in the duodenum (P = 0.0001), but a positive culture at no other site readily predicted the presence of Candida at yet another site. Importantly, there was no correlation between the presence or absence of Candida in either oral or rectal swabs and colonization at other anatomic sites within the gastrointestinal tract. These findings are important in liver transplantation, particularly in those cases in which the bowel has been opened to create a choledochojejunostomy anastomosis. The operative attempts to reduce gastrointestinal fungal carriage using oral antifungal agents may be justified before liver transplantation in an effort to lower the risk of posttransplantation fungal infections, particularly in those patients expected to have a Roux-en-Y choledochojejunostomy biliary reconstruction.

Body Fluids↗

Factors associated with the development of post-transplant lymphoproliferative disease (PTLD) in Epstein-Barr virus (EBV)-seronegative adult liver transplant recipients.

Epstein-Barr virus (EBV) infection is recognized as the principal aetiological factor in the pathogenesis of post-transplant lymphoproliferative disease (PTLD), particularly when primary EBV infection occurs after transplantation. We analysed, using a time-dependent proportional hazards model, the factors associated with development of PTLD in 40 adult liver transplant recipients who were seronegative for EBV prior to transplantation. Of 40 patients, 13 (33%) had a tissue diagnosis of PTLD at a median time of 126 days after transplantation. The multivariate analysis showed that prior CMV disease, the number of steroid boluses given and the number of units of RBC and FFP transfused were significant risk factors for development of PTLD.

Adult↗

Diagnosis of cytomegalovirus infections by shell vial assay and conventional cell culture during antiviral prophylaxis.

A total of 3,552 specimens for conventional cytomegalovirus (CMV) culture and shell vial assay for CMV immediate-early antigen were obtained during a prospective randomized trial for prophylaxis of CMV disease after liver transplantation. Prophylaxis with ganciclovir for 2 weeks and then high-dose acyclovir for 2.5 months was compared with high-dose acyclovir alone for 3 months. During the first 12 weeks after transplantation, when the patients were on prophylaxis, there were significantly more clinical samples positive by the shell vial assay and negative by standard culture in comparison with the number of samples obtained from weeks 13 to 24, after prophylaxis was discontinued, that were positive by the shell vial assay and negative by standard culture. In contrast, significantly fewer samples were positive by both the shell vial assay and standard culture during the first 12 weeks compared with the number obtained 13 to 24 weeks after transplantation that were positive by both methods. Samples positive by the shell vial assay only were obtained significantly more frequently from patients with asymptomatic than symptomatic CMV infections, while samples positive by both methods were obtained significantly more often from patients with symptomatic CMV infection. It was concluded that antiviral prophylaxis with high-dose acyclovir or ganciclovir and then high-dose acyclovir and asymptomatic CMV infection are associated with a decrease in the level of CMV isolation by standard cell culture in comparison with that by the shell vial assay.

Acyclovir↗

Detection of cytomegalovirus in formalin-fixed paraffin-embedded donor, native and allograft liver tissue using a multiplex polymerase chain reaction-liquid hybridization assay.

A multiplex polymerase chain reaction (PCR)-liquid hybridization assay detecting a minimum 10 fg of cytomegaloviral (CMV) DNA has been developed. This assay successfully detected viral nucleic acids in 25/26 (96.2%) routinely embedded allograft liver biopsies with CMV hepatitis. No CMV DNA was detected in 15 native and 12 donor liver tissues sampled at the time of liver transplantation. These results indicate that archived formalin-fixed, paraffin-embedded liver tissues obtained from patients with significant liver disease can be successfully analyzed for CMV by PCR, retrospectively. Failure to detect CMV in native and donor livers implies that any latent virus present within these tissues is very focally distributed, or is below the threshold of detection applicable to PCR.

Base Sequence↗

The impact of blood transfusion on the occurrence of pneumonitis in primary cytomegalovirus infection after liver transplantation.

The influence of blood transfusion, and particularly the transfusion of blood from cytomegalovirus (CMV)-seropositive donors, on the incidence of primary CMV infection following liver transplantation was studied prospectively in 29 consecutive CMV-seronegative adult liver transplant recipients. Fourteen patients received a liver graft from a CMV-seropositive donor (Group A), whereas for 15 patients, the donor was CMV seronegative (Group B). Eleven patients (79%) in Group A but only two (13%) in Group B developed CMV infection (odds ratio, 23.8; 95% confidence interval, 3.5-169.4). In five Group A patients, primary CMV infection resulted in pneumonitis. There was no statistical difference in the total number of blood units and the number of units of CMV-seropositive blood given to patients who did or did not develop CMV infection in both Groups A and B (odds ratio for unit of CMV-seropositive blood transfused, 1.07; 95% confidence interval, 0.96-1.19). However, Group A patients who developed CMV pneumonitis received a higher total number of blood units (median, 44) and of CMV-seropositive blood units (median, 18) than did patients who developed other CMV infections (asymptomatic CMV, CMV syndrome, or CMV hepatitis), who received a median of 9 total units of blood and 5 units of CMV-seropositive blood (p = 0.004). It is concluded that the total number of blood units and of CMV-seropositive blood units transfused does not have an effect on the incidence of primary CMV infection after liver transplantation, but it does have an impact on the severity of the infection in recipients of a CMV-seropositive allograft.

Blood Transfusion↗

The influence of HLA matching on cytomegalovirus hepatitis and chronic rejection after liver transplantation.

Previous findings in liver transplantation patients have raised the concept that HLA plays a dualistic role. HLA matching will reduce rejection but may augment MHC restricted cellular immune mechanisms of liver allograft injury. To evaluate this concept, we studied CMV hepatitis in 399 FK506-treated liver transplant patients, including 355 cases for which complete HLA-A,B,DR,DQ typing information was available. CMV hepatitis developed in 25 patients, and 17 of them (or 68%) showed a one or two HLA-DR antigen match with the donor. In contrast, HLA-DR matches were found in only 35% of 330 patients without CMV hepatitis (P = 0.005). No significant associations were seen for HLA-A, HLA-B, and HLA-DQ antigens. In pretransplant CMV-seronegative patients with seropositive grafts (n = 39), the frequency of CMV hepatitis was 44% for HLA-DR-matched livers but 14% for HLA-DR-unmatched livers. In seropositive recipients (n = 187), these frequencies were 12% and 2% for HLA-DR-matched and unmatched liver grafts. Chronic rejection developed in 29 patients (or 8%) during a follow-up between 10 and 24 months after transplantation. Its incidence was higher in the CMV hepatitis group (24% vs. 6%) (P = 0.007). Although no associations were found between HLA matching and the incidence of chronic rejection, there was an earlier onset of chronic rejection of HLA-DR-matched livers irrespective of CMV hepatitis. These findings suggest that an HLA-DR match between donor and recipient increases the incidence of CMV hepatitis in both primary and secondary CMV infections. Although HLA compatibility leads to less acute cellular rejection, it is suggested that DR matching may accelerate chronic rejection of liver transplants, perhaps through HLA-DR-restricted immunological mechanisms toward viral antigens, including CMV.

Chronic Disease↗

Constitutively vancomycin-resistant Enterococcus faecium resistant to synergistic beta-lactam combinations.

Vancomycin resistance among enterococci has recently been recognized. Synergy between vancomycin and penicillin has been shown in vitro for isolates of Enterococcus faecium resistant to both of these antibiotics. We describe three isolates of vancomycin-resistant E. faecium which demonstrate unique phenotypic characteristics. The isolates exhibited high-level resistance to both vancomycin and teicoplanin, consistent with the VanA phenotype. However, resistance in these isolates could not be induced or cured, and mating experiments failed to detect a transfer of resistance. The combination of vancomycin and penicillin did not significantly change the MIC of penicillin for any of the three isolates. Immunoblotting with polyclonal anti-VanB antibody showed no reaction with the cellular proteins of these strains. Probing with a vanA oligonucleotide revealed hybridization with chromosomal but not plasmid DNA. The mechanism of constitutive resistance of those strains remains unclear. A second mutational change, perhaps involving PBP 5, may explain the presence of resistance to synergistic combination penicillin-vancomycin therapy. In vitro evaluation of penicillin-vancomycin should be carried out in all clinical cases where this therapeutic regimen is being considered.

Adult↗

CNS aspergillosis in organ transplantation: a clinicopathological study.

The clinical characteristics and neuropathological findings of 22 organ transplant recipients with CNS aspergillosis were reviewed. Thirteen patients had liver, six kidney, two heart and one had cluster transplants. The most frequent neurological symptoms were alteration of mental status (86%), seizures (41%) and focal neurological deficits (32%). Meningeal signs were less common (19%). Aspergillus spp invasion of the blood vessels with subsequent ischaemic or haemorrhagic infarcts, and solitary or multiple abscesses were the predominant neuropathological findings. The lungs were the probable portal of entry; however, isolated CNS aspergillosis was seen in two patients. Antemortem diagnosis of the infection was made in half of the patients. Concomitant diabetes mellitus was noted in 59% of the patients and bacterial or other severe infections in 86%. No specific clinical or pathological pattern could be identified among patients with different types of organ transplants. In addition CNS aspergillosis was preceded by organ rejection and the need for intense immunosuppression and retransplantation in the majority of the patients.

Adolescent↗

Liver transplantation and related infections.

Liver transplantation is complicated by higher rates of bacterial and fungal infection and higher infectious mortality than are other forms of solid organ transplantation. The excess morbidity and mortality are largely confined to the first few months after transplantation and appear to be caused by the technical complexity of the operation and perhaps the residual end organ effects of chronic liver failure. The most common infections seen are bacterial infections in the abdomen and hepatobiliary system, systemic cytomegalovirus infections, bacterial pneumonias, and invasive candidiasis. In addition, systemic viral infections affecting the allograft such as hepatitis B and hepatitis C, adenovirus, and herpes simplex virus have been important clinical problems. The intensity and wide array of infectious problems seen in this population represents a challenge to clinicians to develop strategies for treatment and prophylaxis that will ensure good long-term survival to patients receiving liver transplants.

Chronic Disease↗

Primary cutaneous fungal infection after solid-organ transplantation: report of five cases and review.

Solid-organ transplant recipients who are receiving immunosuppressive therapy are at increased risk of acquiring opportunistic infections, particularly fungal infections. We present the cases of five liver transplant recipients who developed primary cutaneous opportunistic fungal infections that remained localized to the skin. These cases are compared with 27 previously reported cases of primary cutaneous fungal infections. In these previously reported cases, administration of systemic antifungal medications, including amphotericin B, ketoconazole, griseofulvin, and miconazole, resulted in a 71% survival rate. Medical and surgical therapy together resulted in an 86% survival rate, and surgical excision resulted in a 100% survival rate. Thus, regardless of the age of the patient, type of immunosuppressive therapy, clinical presentation, or organisms involved, surgical excision yielded the highest cure rate. When possible, surgical excision should be performed on solid-organ transplant recipients who acquire opportunistic fungal infections.

Adult↗

Factors associated with invasive lung aspergillosis and the significance of positive Aspergillus culture after liver transplantation.

From January 1981 to December 1990, 2180 patients underwent orthotopic liver transplantation at the University of Pittsburgh. Thirty-two patients (1.5%) were identified with invasive aspergillosis (29 lung, 2 intraabdominal, 1 meningitis). Of 29 patients with invasive lung disease, only 23 (79%) had positive culture (Aspergillus fumigatus, 20; Aspergillus flavus, 3). Forty-eight variables were analyzed and compared in 23 patients with invasive disease with positive cultures and 9 patients with colonization only. The variables associated with pulmonary invasive disease, by univariate analysis, were surgical time (P = .03), presence of laparotomies (P = .02), higher creatinine level at time of Aspergillus isolation (P = .01), and use of OKT3 (P = .02). However, in a multivariate analysis, only the last two (creatinine, OKT3) were associated with invasive lung aspergillosis. Of 4 patients with positive abdominal wound culture, 2 had local invasive aspergillosis. Therefore, positive cultures of Aspergillus organisms from respiratory secretions and wound drainage may represent invasive disease and should not be ignored.

Adult↗