Evaluation of serological screening of cadaveric sera for donor selection for cornea transplantation.

Human corneas are explanted for grafting as late as 72 h after death, for example, from medical examiner cases. Currently, infection of the donor with human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) is excluded in most cornea banks by serological testing of the cadaveric serum only. The reliability of this strategy was investigated by testing paired cadaveric and premortem sera of 33 potential donors. Results were discordant in 17 of 33 donors by at least one assay. Most frequently, HBsAg enzyme-linked immunosorbent assay (ELISA) yielded false-positive results with the cadaveric serum (16 of 33 serum pairs). Virus safety of the graft was affected in a single case, which was HCV antibody negative in the cadaveric serum, but positive in the premortem serum (confirmed by HCV-RIBA strip immunoassay). Forensic DNA profiling by polymerase chain reaction (PCR) of both serum samples confirmed that these were derived from the same individual. In conclusion, the results indicate that serological testing of cadaveric sera is not a reliable method for screening of potential cornea donors, and may not be sufficient for the virus safety of cornea grafts. Therefore, other screening strategies such as detection of viral nucleic acids by PCR should be evaluated.

The long-term course of hepatitis C after kidney transplantation.

Patients with chronic hepatitis run the risk of developing progressive liver disease during immunosuppressive therapy after kidney transplantation. To determine the impact of chronic hepatitis C on morbidity and mortality we analyzed 162 anti-HCV positive of 1241 renal-grafted patients (prevalence 13.1%; 84.9% HCV RNA positive) regularly surveyed in our outpatient clinic between 1992 and 1994. The mean age at transplantation was 44.5 (6-69) years, and follow-up after grafting was 7.4 (0.1-23.9) years. The immunosuppressive regimen and frequency of rejection episodes in HCV-infected patients were comparable to the total population. Only 4.3% (5/117) of the anti-HCV positive, HBV negative patients living with functioning grafts developed a markedly compromised liver function. Fifteen (9.3%) of the HCV-infected patients died, but none suffered from posthepatitic cirrhosis. An additional retrospective analysis of causes of death after transplantation prior to 1992 revealed that liver disease had only been responsible for 2% of the deaths (7 of 324) in the HBsAg negative population (n= 1901). In contrast, the predominant cause of death in the HBsAg positive population (n=76) was posthepatitic cirrhosis in 58% (15 of 26). Thus, kidney transplantation in patients with replicative hepatitis C and normal liver function appears to be justified because of low early and late morbidity and mortality due to chronic liver disease. HBV infection and hemosiderosis substantially increase the risk of chronic liver disease in renal transplant recipients with hepatitis C.

Management of herpes simplex virus type 1 pneumonia following liver transplantation.

Interstitial pneumonia caused by Herpes simplex virus type 1 (HSV-1) is a severe complication of orthotopic liver transplantation (LTX). The records of patients were reviewed who had an LTX at the age of 16 years or older between 1991 and 1994 with a mean follow-up of 21 months (range, 10 to 44 months). Six patients were included who had fever of > 38 degrees C, deterioration of arterial blood gases, radiological evidence of interstitial pneumonia and proof of HSV-1 in bronchoalveolar lavage fluid. All patients were anti-HSV-IgG positive before LTX. All patients were successfully treated with intravenous acyclovir, mechanical ventilation and reduced immunosuppression. Three patients who received cyclosporin A had a rejection which was successfully treated by switching to FK 506. Four patients were discharged in good health. One patient died 36 months after LTX of an unrelated cause. One patient died of urosepsis on postoperative day 139. Acyclovir together with mechanical ventilation and reduced immunosuppression proved to be an effective treatment for HSV-1 pneumonia following LTX.

[Q-fever associated myocarditis in a 14-year-old boy]. / Q-Fieber-assoziierte Myokarditis bei einem 14jährigen Jungen.

A 14-year-old boy presented with the symptoms and clinical signs of myocarditis. Ventricular arrhythmias were the main manifestation. Dilated left ventricle with slightly impaired contractility and spongy appearance of the myocardium were also noted. Laboratory signs of an acute infectious disease were absent, but a significant rise in the complement fixation titer for Coxiella burnetii was observed. Treatment with oral tetracycline for 6 months resulted in improvement of ventricular arrhythmias and normalization of left ventricular dimensions and structure over the following months. Cardiac involvement in Q fever is rare, and with it endocarditis is usually seen as a chronic form of the disease. Myocarditis associated with Q fever has been reported only in some rare cases but not in children. The case reported here illustrates that the diagnosis of Q fever should also be considered in a case of myocardial involvement in an infectious disease of unknown etiology.

Influence of formalin fixation on the detection of cytomegalovirus by polymerase chain reaction in immunocompromised patients and correlation to in situ hybridization, immunohistochemistry, and serological data.

The possibility of detecting cytomegalovirus (CMV) in formalin-fixed tissues by polymerase chain reaction (PCR) was evaluated in necroposies from lung tissues in a total of 24 patients who either had received organ transplants or were immunocompromised. PCR using two different pairs of primers for amplification of the major immediate early antigen of CMV was performed on fresh tissues and tissues fixed for 24, 48, and 72 h in neutral buffered formalin and compared to immunohistochemistry (IHC) and in situ hybridization (ISH). The fresh tissues of nine patients with serological evidence for acute CMV infection were all positive for CMV by PCR. After formalin fixation, the majority of the patients failed to show distinct signals with one or both pairs of primers as measured by densitometry. In contrast to this, fresh tissues of 15 patients without signs of an acute CMV infection were found either negative or weakly positive by PCR. Using IHC or ISH, positive results were observed only in five of nine and four of nine patients with acute CMV infection, respectively. These data demonstrate that, if only formalin-fixed tissue is available, PCR for CMV detection should be performed using two pairs of primers and should be supported by IHC.

Hepatitis B vaccination of immunosuppressed heart transplant recipients with the vaccine Hepa Gene 3 containing pre-S1, pre-S2, and S gene products.

The antibody response of immunosuppressed heart transplant recipients to vaccination with the hepatitis B (HB) virus vaccine Hepa Gene 3 (HG-3), containing HB virus pre-S1, pre-S2, and S gene products, was examined. Three heart transplant recipients who had been vaccinated preoperatively against HB responded well to the vaccination. Five of 38 patients (13.2%) vaccinated postoperatively before HG-3 vaccination with the second-generation vaccine Gen-H-B-Vax-D (37 without and 1 with detectable anti-HBs response) and 3 of 24 (12.5%) without previous HB vaccination developed protective anti-HBs titers (greater than 10 U/l) after immunization with the HG-3 vaccine. The low response rate (8/62, 12.9%) found for postoperatively vaccinated patients indicates that heart transplant recipients should be vaccinated against HB before immunosuppressive medication.

Nosocomial hepatitis B virus infections in cardiac transplant recipients transmitted during transvenous endomyocardial biopsy.

Between March 1986 and September 1990, 67 of 243 cardiac transplant recipients in outpatient care at our clinic became hepatitis B virus surface antigen (HBsAg) positive after operation. The HBsAg of 63 patients belonged to the subtype ay, suggesting a common source of infection. These 63 cases and 103 controls with negative hepatitis B virus (HBV) serology were studied in order to analyse the outbreak. The sources of infection were patients who were chronic HBsAg carriers. Infection was transmitted at the time of endomyocardial biopsy, if performed on the same day and in the same room after biopsy of an HBsAg positive patient. The most likely mode of HBV transmission was droplet contamination of instruments and/or medication vials used for subsequent patients. Performing biopsies on HBsAg positive and negative patients in separate rooms resulted in the termination of the outbreak.

Failure of vaccination against hepatitis B with Gen H-B-Vax-D in immunosuppressed heart transplant recipients.

Some 86 heart transplant recipients under immunosuppressive therapy were vaccinated against hepatitis B using the vaccine Gen H-B-Vax-D, but 95.3% failed to develop protective levels of HBs-specific antibody (more than 10 U/l) after the third vaccination.

[The AIDS problem in accident surgery]. / AIDS-Problematik in der Unfallchirurgie.

In trauma surgery there is a particularly high proportion of patients in the age group most at risk of infection with AIDS. The result of an epidemiological study in our patients (HIV screening of all patients scheduled for surgery at a trauma center over 18 months) showed a prevalence of 0.1%. Specific therapeutic strategies must be developed to deal with the weakened immunity of HIV-infected patients. Fracture treatment in HIV-infected hemophiliacs is a special problem. Homogenous bone transplantation is described with reference to HIV. The particular danger of injury in trauma surgery is also investigated. The chain of infection is illustrated and used to demonstrate the precautions that can be taken against nosocomial HIV infections. Following infection with fluids containing HIV, specific measures must be taken. The legal aspects of HIV-antibody testing in the Federal Republic of Germany are elucidated. Finally, the problems of general preoperative HIV-antibody testing are discussed.

Method for determining the concentration of influenza virus antihemagglutinin antibody molecules, the number of epitopes per virus particle and the equilibrium constant of virus antibody interaction.

A novel technique for the determination of the concentration of influenza virus antihemagglutinin antibody molecules (A), of the equilibrium constant (K) and of the number of epitopes recognized per virus particle (s) is described. The test utilizes measurements of virus-antibody interaction both in a photometric hemagglutination inhibition test and in the method of equilibrium filtration and is based on the following principle: the number of antibody molecules adsorbed per virus particle at the antibody dilution (1/d50) yielding 50% hemagglutination inhibition in a photometric HI test was found to be constant, providing an estimate of the concentration of bound antibody at the dilution d50. The corresponding concentration of free antibody is calculated by use of parameters determined by equilibrium filtration and the antibody concentration is obtained as sum of bound and free antibody. The antibody concentration found is used for calculating the equilibrium constant K and the number of epitopes recognized per virus particle.

[Hepatitis C virus (HCV) antibodies in German blood donors--a pilot study]. / Hepatitis-C-Virus-(HCV)-Antikörper bei deutschen Blutspendern--eine Pilotstudie.

A new EIA-test to detect Hepatitis C antibody (ORTHO Diagnostic Systems) has been evaluated in four blood transfusion services in FRG (Hamburg, Hannover, Springe, Frankfurt). Among 3,123 specimens, 18 (0.58%) reacted initially positive, 13 (0.42%) remained positive after repeat testing. A detailed analysis revealed remarkable differences: blood donors from the northern part of Germany were less frequently positive than donors from the southern region (0.24% vs. 0.79%), repeat donors had a higher HCV-antibody incidence than first-time donors (0.48% vs. 0.29%). Similar differences were observed between remunerated and non-remunerated donors (0.24% vs. 0.53%), as well as between donors from rural and urban areas (0.34% vs. 0.46%). In contrast to other investigators, only a weak correlation between elevated ALT-levels (greater than 50 IU/ml) and anti-HCV seropositivity rate has been found.

[Importance of screening for antibodies to cytomegalovirus in organ transplantation]. / Bedeutung der Untersuchung auf Antikörper gegen Cytomegalievirus bei Organtransplantationen.

The influence of screening blood donors for CMV antibodies on the incidence of CMV infection after transplantation was examined in 81 heart and 81 liver transplant recipients. All heart recipients received CMV-seronegative blood, while the liver recipients were given both CMV-positive and CMV-negative blood, due to the large number of units of blood required. In CMV seropositive organ recipients CMV reactivations occurred at about the same rate in heart and liver recipients (60.4% to 63.4%), independently from the CMV status of the organ donor. In CMV seronegative organ recipients a CMV infection rate of 60-70% was recorded for the recipients of CMV-positive organs. The recipients of hearts from CMV-IgG-negative donors remained CMV-negative. By contrast, 5 CMV infections occurred in recipients of CMV-negative livers. These CMV infections were probably caused by transfusion of CMV-IgG-positive blood. Our results suggest that CMV negative recipients should be given exclusively CMV negative blood, if possible.

[Differential diagnosis of parotid tumors: toxoplasmosis lymphadenitis of the parotid gland]. / Zur Differentialdiagnose von Parotistumoren: Die Toxoplasmose-Lymphadenitis in der Glandula parotis.

The most common clinical symptom of toxoplasmosis in adults is a cervicofacial lymphadenopathy. The cat is very important in the epidemiology of toxoplasmosis, but contact with cat excreta is most uncommon. The cause of oral transmission in adults is more likely to be eating undercooked contaminated meat containing tissue cysts, particularly raw pork. Toxoplasmosis as a cause of lymphadenopathy is an unusual, and normally postoperative, finding after parotidectomy for a "tumour". In the last 8 years we have seen ten patients with an acute toxoplasmosis infection. We report two patients showing clinical signs of a parotid gland tumour in whom we demonstrated an intraglandular toxoplasmosis lymphadenopathy before operation. We treated these patients successfully using pyrimethamine and sulphonamide, so that surgery was unnecessary.

Hyperimmuneglobulin for cytomegalovirus prophylaxis following heart transplantation.

Cytomegalovirus continues to be an important cause of morbidity and mortality following organ transplantation. In a series of 75 heart transplant patients, we have compared two protocols for prophylactic administration of CMV hyperimmuneglobulin. The first group of patients received immunoglobulin on the operative and on the tenth postoperative days. The second group of patients received immunoglobulins on the operative day, and repeatedly with each period of increased immunosuppression. With repeated doses of immunoglobulin prophylaxis, the incidence of CMV reactivation and the clinical severity of CMV infection were both significantly reduced. A reduction in the incidence of CMV infection in recipients who were seronegative preoperatively was also observed. (5/8 vs. 7/25 patients; P = 0.06). We conclude that repeated administration of specific hyperimmuneglobulin with each period of increased immunosuppression following heart transplantation has a beneficial effect on both CMV reactivation and infection.

[Hyperimmunoglobulin treatment in CMV infections following heart transplantation]. / Hyperimmunglobulinbehandlung bei CMV-Infektionen nach Herztransplantation.

Clinically manifest cytomegalovirus (CMV) infections, with and without pulmonary involvement, occurred in two patients after heart transplantation. The diagnosis was confirmed immunologically. After administration of CMV hyperimmunoglobulin and prophylactic antibiotics and a reduction of immunosuppressives, rapid clinical improvement ensued so that both patients were discharged from hospital after seven and ten days, respectively.

[Frequency and serologic diagnosis of cytomegalic infections following heart transplantation in 1986]. / Häufigkeit und serologische Diagnose von Cytomegalie-Infektionen nach Herztransplantation 1986.

Of 60 patients receiving heart transplants in 1986, 45 were examined serologically for at least 50 days: 28 had a cytomegalovirus (CMV) infection and 12 had symptoms of a CMV infection. In those patients who before transplantation were serological negative for CMV but had received organs from CMV-IgG positive donors, the incidence of the disease was highest. No CMV infection was observed among CMV-IgG negative recipients of CMV-negative donor hearts.