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P E Hermans

Publications and source records attributed to P E Hermans.

At least 19 recordsLinked to original sources

Lack of association between cytomegalovirus infection, HLA matching and the vanishing bile duct syndrome after liver transplantation.

In this study we evaluated the association between cytomegalovirus infection alone or in relation to human leukocyte antigen matching and the development of vanishing bile duct syndrome, a form of chronic hepatic allograft rejection. A total of 81 consecutive liver transplant recipients were studied. Cytomegalovirus infection developed in 46 recipients (57%), and vanishing bile duct syndrome occurred in 9 recipients (11%). Cytomegalovirus infection developed in only five of the nine patients with vanishing bile duct syndrome. Univariate analysis of pretransplant recipient/donor cytomegalovirus serological tests and human leukocyte antigen typing showed they were not significant risk factors for the development of vanishing bile duct syndrome. Time-dependent analysis of cytomegalovirus infection after transplantation as a risk factor for vanishing bile duct syndrome, in a multivariate analysis with human leukocyte antigen match, showed no statistical significance. In our study, no association was found between cytomegalovirus infection alone or in relation to class I or II human leukocyte antigen match and the subsequent development of vanishing bile duct syndrome.

Acyclovir

Early diagnosis of cytomegalovirus hepatitis in liver transplant recipients: role of immunostaining, DNA hybridization and culture of hepatic tissue.

Immunostaining techniques that use a monoclonal antibody against an early cytomegalovirus antigen or a polyclonal antibody, in situ DNA hybridization and inoculation of cell cultures for the detection of cytomegalovirus from liver biopsy specimens were studied in 20 liver transplant patients with cytomegalovirus hepatitis, as defined by histological criteria. A total of 108 liver biopsy specimens from 20 patients with a diagnosis of cytomegalovirus hepatitis (obtained per protocol at 7, 21, 90, and 180 days or whenever liver dysfunction occurred), which had previously been examined histologically and in cell culture, were again studied by recutting the liver tissue for histological examination, DNA hybridization and immunostaining with monoclonal or polyclonal antibodies to cytomegalovirus. In 5 of 20 patients, the diagnosis of cytomegalovirus hepatitis could have been made earlier (mean = 9.6 days) by immunostaining with a monoclonal antibody. Of 47 biopsy specimens with cytomegalovirus inclusion bodies, the sensitivity and specificity of the diagnostic procedures were immunostaining with monoclonal antibody (84% and 90%) and polyclonal antibody (72% and 97%), in situ DNA hybridization (72% and 100%) and cell culture detection (52% and 95%), respectively. Immunostaining with a monoclonal antibody against an early CMV antigen frequently detected cytomegalovirus infection in the liver allograft earlier than identification of typical histological inclusion bodies. DNA in situ hybridization was less sensitive than other techniques but highly specific; cytomegalovirus cell culture lacked sensitivity compared with the other procedures.

Adult

Bacterial infections after liver transplantation.

Infection is a common complication of orthotopic liver transplantations and a major cause of mortality. Of the different types of infection, severe bacterial infections are the most common. The majority (81%) of bacterial infections occur within the first two months after liver transplantation. The most frequent site of infection is the abdomen (intrahepatic or extrahepatic abscesses, cholangitis, and peritonitis). Bacteremia is a marker of mortality, and the majority of bacteremia cases are secondary to another bacterial infection site. The causative organisms vary among different centers. In some, gram-negative organisms are more common (66%); in one center, however, gram-positive microorganisms predominate (66%). In the latter center, the use of nonabsorbable antibiotics, which eradicate gastrointestinal aerobic gram-negative microorganisms, may explain this microbiologic difference. The main risk factor predisposing to bacterial infection appears to be the duration of the transplantation operation, especially beyond 12 hours. Of the deaths resulting from infection, 81% were caused by bacterial infection.

Abscess

Idiopathic granulomatosis manifesting as fever of unknown origin.

Twenty patients with fever of unknown origin were found to have idiopathic granulomatosis of the liver, lymph nodes, spleen, or bone marrow. At the time of initial examination, these patients had persistent or recurrent fever and pronounced constitutional symptoms but few physical findings. The most common laboratory abnormalities were increased erythrocyte sedimentation rate in 18, abnormal results of liver function tests in 12, anemia in 11, and hypergammaglobulinemia in 10. Of the 20 patients, 14 required corticosteroids at the beginning of the illness for control of symptoms, especially fever. After 5 to 10 years of follow-up, an alternative diagnosis had been established in 5 of the 20 patients. Of the remaining 15 patients with fever and idiopathic granulomatosis, 6 are still receiving corticosteroids. Corticosteroid treatment did not result in progression or dissemination of an unrecognized infection. No clinical or laboratory abnormality helped to predict the need for long-term corticosteroid treatment.

Adult

The first 100 liver transplantations at the Mayo Clinic.

Between March 1985 and June 1987, the first 100 liver transplantations at the Mayo Clinic were performed in 83 patients (primarily adults). The most frequent diagnoses were chronic active hepatitis (in 24 patients), primary sclerosing cholangitis (in 22), and primary biliary cirrhosis (in 20). The median operating time was 406 minutes, and the median usage of erythrocytes was 13.2 units. A venovenous bypass was used in all patients older than 10 years of age. Hepatic artery thrombosis occurred in 10% of the 100 transplants. A choledochocholedochostomy was done in 58 patients and a choledochojejunostomy in 25 patients. Revision of the biliary anastomosis was necessary in 9 of the 83 patients (11%). Rejection, diagnosed by clinical and histologic criteria, occurred in 50 patients (60%) and was treated with a corticosteroid bolus, followed by OKT3 (monoclonal antibody) treatment if necessary. Selective bowel decontamination helped prevent infections; only 16 bacteremias occurred, 1 of which was caused by a gram-negative organism. Fungal infections were rare. Cytomegalovirus infection occurred in 47 patients (57%). Of the 83 patients, 16 required retransplantation, in 11 of whom graft rejection had occurred. One- and 2-year patient survival was 83% and 70%, respectively. Although problems still remain, liver transplantation is a reasonable option for patients with end-stage liver disease.

Academic Medical Centers

Rapid shell vial culture and tissue histology compared with serology for the rapid diagnosis of cytomegalovirus infection in liver transplantation.

Sixty-six patients who had undergone 78 liver transplantations, with no detectable cytomegalovirus (CMV) infection before transplantation, were studied to assess the value of CMV serology compared with the rapid detection of the virus in shell vial cell cultures or histology for the diagnosis of (1) the first evidence of infection, (2) symptomatic disease, and (3) asymptomatic infection. Of 28 evaluable patients, shell vial cell culture assay and histologic findings provided the first evidence of CMV infection earlier in 22 (79%) or at the same time as the serologic response in 5 (18%). Serologic results yielded the first indication of CMV infection in only 1 of these 28 patients (3%). Of 17 evaluable transplantations in 15 patients in whom symptomatic invasive disease developed, shell vial culture or histology provided a laboratory diagnosis of CMV infection earlier or at the same time as serologic responses in 16 (94%). Similarly, shell vial culture or histology provided evidence of CMV infection in 10 of 11 patients (91%) who had asymptomatic CMV infection and remained asymptomatic. Urine surveillance cultures yielded the first evidence of CMV infection in 14 of 19 patients who initially had an asymptomatic infection, of which 6 became symptomatic. Culturing of the blood with use of the rapid shell vial technique showed that viremia preceded CMV organ involvement in 7 of 10 patients. We recommend culture by the shell vial assay as the most rapid and sensitive method of determining CMV infection in liver transplant patients.

Cytomegalovirus Infections

Incidence, distribution, and outcome of episodes of infection in 100 orthotopic liver transplantations.

Of 83 patients who underwent 100 orthotopic liver transplantations, 53 had a single transplant procedure and at least 6 months of follow-up. In this main study group of 53 patients, major infections developed in 28 (53%) (a mean of 1.8 major episodes per infected patient). Of 51 major infections, 27 were bacterial, 19 were viral, 3 were protozoan, and 2 were fungal. Of the 27 bacterial infections, 22 (81%) occurred in the first 2 months after transplantation. Of the 40 bacterial isolates in the 27 bacterial infections, gram-positive aerobic bacteria were isolated in 26 (65%), anaerobic bacteria in 8 (20%), and aerobic gram-negative bacteria in 6 (15%). Only 1 of 16 bacteremic episodes was due to a gram-negative aerobic bacterium. Cytomegalovirus (CMV) infection occurred in 30 of the 53 patients (57%) and was symptomatic and invasive in 18. CMV infection was diagnosed a mean of 26 days after transplantation. Infections due to Pneumocystis carinii occurred later (2 to 3 months after transplantation). Death from infection occurred in 4 of the 53 patients (8%). In the group of 16 patients with two or more liver transplantations, fungal infection occurred in 2 and CMV infection in 13. In all 16 patients who underwent more than one liver transplantation, a major infection developed. The observations made in the main study group were consistent with findings in 13 patients with one liver transplantation but less than 6 months of follow-up. Infection is a major complication after liver transplantation, generally occurring in the first 2 months. Our observations suggest that the use of selective bowel decontamination may be associated with a relatively lower incidence of gram-negative aerobic bacterial infections.

Bacterial Infections

Cytomegalovirus hepatitis in liver transplantation: prospective analysis of 93 consecutive orthotopic liver transplantations.

Ninety-three consecutive orthotopic liver transplantations in 78 patients were followed prospectively to study the incidence of cytomegalovirus (CMV) hepatitis. CMV hepatitis occurred in 13 (17%). The diagnosis was established by both histology and culture in 5, only by histology in 6, and only by culture in 2. All 13 patients had CMV viruria and 9 had viremia at diagnosis. CMV hepatitis developed in 64% of CMV-seronegative (pretransplantation) patients who received a liver from a CMV-seropositive donor, compared with 3% or 6% of CMV-seropositive patients who received a liver from a CMV-seronegative or CMV-seropositive donor, respectively (P less than .001). CMV hepatitis was not a cause of fulminant or irreversible liver dysfunction in any of the 13 cases. Ganciclovir was administered to 6 of the 13 patients and was associated with clinical and virologic cure in 5. CMV hepatitis was self-limited in patients not treated with ganciclovir (illness less severe). The presence of inclusions within the liver tissue correlated with active disease.

Age Factors

Selective bowel decontamination to decrease gram-negative aerobic bacterial and Candida colonization and prevent infection after orthotopic liver transplantation.

Gram-negative bacterial and fungal infections are a major cause of morbidity and mortality following liver transplantation. We therefore used selective bowel decontamination (SBD) to eliminate the endogenous source of gram-negative aerobic bacteria and Candida pathogens in an attempt to reduce the high incidence of infection related to these organisms. Thirty consecutive patients undergoing liver transplantation were treated with SBD starting 3 days prior to donor search and continuing for 21 days postliver transplantation. Selective bowel decontamination consisted of administering nonabsorbable antibiotics (Polymixin E, gentamicin, Nystatin) and a low bacterial diet. Surveillance cultures of the throat and rectum were obtained to monitor efficacy of selective bowel decontamination. In addition, in the posttransplant period, tracheal, wound, blood, and bile cultures were obtained to screen for gram-negative bacterial and Candida colonization and infection. Our baseline surveillance culture revealed that 29/30 (97%) of recipients were colonized with gram-negative aerobic bacteria and 16/30 (53%) with Candida. Three days after selective bowel decontamination was started, 26/30 (87%) were free of gram-negative bacteria, and 100% were free of Candida colonization of the gastrointestinal tract. There was a similar reduction in the oropharyngeal gram-negative aerobic bacteria and Candida colonization. In the first 30 days following liver transplantation, gram-negative infections were not diagnosed in any of our patients. Following discontinuation of SBD, recolonization of the gastrointestinal tract with gram-negative aerobic bacteria and Candida occurred within 5 days in 26/28 (90%) and 11/28 (35%), respectively. Our study suggests that prophylactive administration of nonabsorbable antibiotics will markedly reduce gram-negative aerobic bacterial and Candida colonization and appears to reduce the high incidence of infection related to these organisms in the early posttransplant period.

Adolescent

Efficacy of ganciclovir in liver and kidney transplant recipients with severe cytomegalovirus infection.

Twelve liver and 5 kidney transplant recipients with severe cytomegalovirus infection were treated with Ganciclovir (7.5 mg/kg/day, intravenously). Ten were evaluable (compatible clinical picture, organ involvement shown histopathologically or by culture, viremia, and absence of concomitant infection). All 17 patients were studied for adverse drug side effects. A total of 9 evaluable patients survived the infection; 1 died during treatment due to infection or drug toxicity. A death 19 days after completion of treatment was due to unrelated causes. Patients became afebrile after 2-9 days (mean, 5.3 days) of treatment. Liver function improved, pulmonary infiltrates cleared, and hypoxemia reversed during therapy. Viremia ceased during therapy in 9 patients; asymptomatic viruria persisted or recurred in 6 of 7 patients studied. No relapses occurred during follow-up (7-17 months; mean, 13 months). Transient neutropenia and thrombocytopenia occurred in 3 and 1 patients, respectively. Ganciclovir appears promising for treatment of severe CMV infection in patients with kidney or liver transplants.

Acyclovir

General principles of antimicrobial therapy.

Use of antimicrobial agents must be tailored to the individual patient, site of infection, and etiologic organism. The choice of drug should be based on efficacy, safety, low toxicity, and acceptable cost. Empiric therapy should be broad enough to cover the pathogens that are suspected of causing the infection, based on the site of infection and the type of host. Definitive therapy may differ from initial therapy and should be started as soon as specific laboratory and clinical data are available. Cautious conservatism is advocated with regard to the use of new antimicrobial agents. The effects of the agents on the microbial ecology and hospital environment should be considered. Judicious use is necessary to prevent antimicrobial pollution.

Anti-Bacterial Agents

Antiviral agents.

Amantadine is well established as the preferred antiviral agent for the prophylaxis of influenza A and may also be beneficial therapeutically when used early in the course of the disease. Idoxuridine is applicable only in the treatment of herpetic keratitis. Currently, acyclovir is the most effective agent for the treatment of herpes simplex and varicella-zoster virus infections. Ribavirin has recently been released for use in aerosol form for severe respiratory syncytial virus infections that occur in infants and young children. Vidarabine, which previously was the drug of choice in the treatment of severe herpetic infections, has now been replaced by the more effective acyclovir. Ganciclovir, an experimental agent, has shown promise against cytomegalovirus infections in patients who have undergone kidney or liver transplantation, but its effects are only temporary in patients who have undergone bone marrow transplantation and patients with acquired immunodeficiency syndrome (AIDS) who have cytomegalovirus infections.

Acquired Immunodeficiency Syndrome

Antifungal agents used for deep-seated mycotic infections.

The main antifungal agents used for deep-seated mycotic infections are the broad-spectrum antifungal drug amphotericin B, the narrow-spectrum agent flucytosine, and the newer broad-spectrum agents ketoconazole, miconazole, and itraconazole. Amphotericin B remains the cornerstone of antifungal therapy. For the treatment of cryptococcal meningitis, the current recommendation is for the combined use of amphotericin B and flucytosine. Published clinical experience with the newer agents is limited. Not all patients from whom fungal agents have been isolated require treatment; the extent of the fungal infection should be determined, when possible, for evaluation of the need for treatment.

Amphotericin B

Vancomycin.

Vancomycin is a narrow-spectrum bactericidal antibiotic used primarily for treatment of serious staphylococcal infections. It is the alternative therapy of choice when the penicillins and cephalosporins cannot be used. Vancomycin is also used in (1) methicillin-resistant Staphylococcus aureus infections; (2) streptococcal endocarditis in conjunction with an aminoglycoside in patients intolerant of penicillin or ampicillin; (3) infections, including those involving prosthetic devices, caused by gram-positive organisms with multiple antibiotic resistance; (4) antibiotic-induced enterocolitis caused by Clostridium difficile; and (5) prophylaxis for endocarditis in patients who are at risk and cannot tolerate a penicillin, cephalosporin, or erythromycin. The major toxic effect associated with the use of vancomycin is ototoxicity, which may develop when serum levels exceed 30 micrograms/ml.

Bacterial Infections

Repeatedly relapsing disseminated histoplasmosis: clinical observations during long-term follow-up.

We report three patients (followed up for 13, 9, and 12 years) who had multiple episodes of disseminated histoplasmosis. Clinically, all three patients had high yields of positive cultures and all developed corticoadrenal insufficiency; all survived the recurrent relapses. One patient had unilateral progressive panophthalmitis, with ocular cultures positive for Histoplasma capsulatum. These relapses occurred despite conventional treatment with large doses of amphotericin B. Prolonged remissions were associated with using small doses of this drug. One patient had a long-term remission while taking ketoconazole daily for more than four years. These patients did not have conditions associated with immunosuppression. Lymphocyte proliferation to mitogens and, in one patient, to histoplasmin, was markedly reduced at the time of relapse and when tested preceding a relapse. All three patients showed a reversal to normal lymphocyte proliferation at the time of the longest last remission.

Female