Klaus Sack

The long persistence of CMV DNA in the blood of renal transplant patients after recovery from CMV infection.

A total of 30–50% of all renal transplant recipients undergo infections caused by human cytomegalovirus. With the introduction of ganciclovir and foscarnet for specific antiviral therapy there is an increasing demand for diagnostic tools that allow the early and rapid identification of CMV as the causative agent of the observed disease. We and others previously showed the direct detection of pp65 antigen in peripheral blood leukocytes to be an excellent marker for active cytomegalovirus infection. In order to establish whether the detection of CMV DNA by the polymerase chain reaction (PCR) sup

The impaired immune response to diphtheria vaccination in elderly chronic hemodialysis patients is related to zinc deficiency

Zinc deficiency causes abnormalities of the immuneresponse. In chronic hemodialysis therapyabnormalities in zinc metabolism as well as animpaired immune response to vaccination have beenreported. Therefore we performed a vaccination studyagainst diphtheria and hypothesized that the responseto diphtheria vaccination is related to serum zincdeficiency in hemodialysis patients. Serum zincconcentrations were assayed in 16 chronic hemodialysispatients (10 male, 6 female; mean age 65 years)without a documented vaccination history againstdiphtheria. Nine of these patients were tripleimmunized against diphtheria while seven received asingle vaccination. The response to diphtheriavaccination was measured by ELISA detecting specificantibodies to diphtheria-toxoid. Seroconversion 6 and12 months after vaccination was defined as thedoubling of antibody titers in patients ≥ 0.1IU/ml prior to vaccination or as titers %gt; 0.1 IU/mlin all other patients. Only 6/16 hemodialysispatients responded to immunization against diphtheriaby specific antibody production (> 0.1 IU/ml).Twelve months after the single injection 3/7 patientsseroconverted while six months after the triplevaccination 3/9 patients responded to immunization.This was not age-dependent, whereas in non-responderswe detected significantly decreased serum zinc levels.In contrast, responders showed similar serum zinclevels as age-matched controls. Furthermore, wemeasured a decreased α2-macroglobulinconcentration only in the responders amongst thehemodialysis patients. Protection against diphtheriaand the immune response to diphtheria vaccination inhemodialysis patients is poor. The failure to respondto active diphtheria vaccination is related to asignificantly decreased serum zinc concentration inhemodialysis patients.

Darmbrand (Enteritis necroticans) Eine historische und aktuelle Übersicht

ZusammenfassungIn den Jahren 1946 bis 1948 trat in Lübeck und anderen Städten Norddeutschlands eine epidemisch verlaufende Infektion auf, die bis dahin nicht bekannt war. Die Erkrankung wurde aufgrund ihrer Morphologie als Darmbrand (Enteritis necroticans) bezeichnet.Untersuchungen ergaben, dass es sich bei dem Infektionserreger um Clostridium perfringens Typ C handelte. In der Folge konnten die Pathogenese der Enteritis necroticans und eine krankheitsauslösende Bedeutung des β-Toxins von Clostridium perfringens Typ C gesichert werden. Entsprechend konnte durch die Immunisierung gegen dieses Toxin die Inzidenz der Enteritis necroticans in Papua-Neuguinea, einem Land, in dem die Erkrankung in bestimmten Regionen noch heute endemisch ist, deutlich gesenkt werden. Wenngleich der Darmbrand in Europa eine kaum noch auftretende Erkrankung ist, so ist mit seinem epidemischen Auftreten besonders in Notstandsgebieten zu rechnen.Die vorliegende Arbeit soll an die in Lübeck aufgetretene Darmbrandepidemie erinnern, eine Darstellung der Epidemiologie, Pathogenese und Therapie der Erkrankung unter Berücksichtigung inzwischen gewonnener Erkenntnisse geben und andere durch Clostridium perfringens induzierte Erkrankungen abgrenzen.AbstractEnteritis necroticans, locally called “Darmbrand”, is a severe and life threatening infectious disease which was epidemic in Northern Germany after World War II. Darmbrand had a limited appearance, occurring only for a few years. In Lübeck many cases were diagnosed in 1946/1948 and the book “Darmbrand, Enteritis necroticans” was published in 1949 by clinicians and pathologists.Enteritis necroticans is also known as a tropical cause of bloody diarrhea and is caused by Clostridium perfringens Type C (type β-toxin). The disease is related to pig feasts in Papua New Guinea. Although necrotizing enterocolitis is now a rather rare disease we must be aware of the appearance of this fulminant entity.This paper represents a review on the historic and current aspects of enteritis necroticans and discusses the epidemiology, pathogenesis and treatment of this disease.

Excessive Polyuria after Renal Transplantation

This article is also accessible online at: http://BioMedNet.com/karger Dear Sir, Besides abnormal urinary rhythm [1], polyuric episodes of 5–8 liters/day occasionally occur after renal transplantation. In most cases diuresis decreases within a few days to normal levels without therapeutic intervention. Such events seem clinically harmless, in the literature no data concerning the frequency or treatment of polyuria in patients after renal transplantation are available. However, we present a patient who developed excessive polyuria of 30–40 liters/ day within 48 h after transplantation. According to her medical history, physical condition, the immunologic circumstances and the uncomplicated surgical treatment, a routine course after renal transplantation was expected in this 57-year-old female patient. After exclusion of extrarenal causes of polyuria (e.g. primary psychogenic polydipsia and polyuria, polyuria by alcohol intake, diabetes mellitus, hypercalcemia, or drug-related interferences, diabetes insipidus centralis), intrarenal defects due to an ischemic lesion were suggested. Urinary analysis revealed complex damage to the proximal and distal parts of the tubular apparatus [2] reducing the effect of endogenous vasopressin, which was adequately elevated in our patient (12.5 pg/ml, RIA) [3], as well as exogenous vasopressin [4, 5] resulting in excessive polyuria with salt-wasting syndrome and tubular proteinuria. Concerned by the clinical complications of this excessive polyuria and its substitution therapy as reviewed recently (e.g. cerebral edema, angina pectoris, shunt occlusion, Staphylococci sepsis) [6] which threatened the success of renal transplantation, pharmacologic intervention to decrease diuresis was started by a stepwise combination of vasopressin, captopril and indomethacin (fig. 1). Fig. 1. Successful drug therapy of polyuria following renal transplantation due to diabetes insipidus renalis accompanied by salt-wasting syndrome. The reduction in daily diuresis (P) as well as FENa (o) after transplantation is shown in relation to a stepwise combination of vasopressin (Pitressin® 20 IU/day or Minirin® 2–10 pumps/day), captopril (Lopirin® 2 ! 25 mg/day) and indomethacin (Amuno® 50–100 mg/day). Stable diuresis within the normal range was achieved. Withdrawal of vasopressin and indomethacin was possible, and the patient was released from hospital care (arrow). ▲

Renin Immunochemistry, Sodium Excretion and Relative Heart Weight in Cyclosporine- or Alimentary-Induced Magnesium Deficiency in Rats

Rats were given a magnesium-(Mg) depleted (Mgd), or a Mg-standard (Mgst) or a Mg-enriched (Mge) diet, with 20 mg/kg/day cyclosporine (Cy) or olive oil per os for 90 days (6 groups). Anti-renin antibody was applied and the percent of renin-positive glomeruli (RI) was taken. Sodium excretion (NaU), relative heart weight (HW), as a measure of hypertension, and total femur Mg were measured. Compared to dietary controls, femur Mg was reduced under Cy and Mgd or Mgst indicating Mg deficiency. RI was higher in all Cy groups (p < 0.01), and Nau was lower in Mgd + Cy and in Mgst + Cy (p < 0.01). Correspondingly, HW was found to be significantly higher in Mgd + Cy and Mgst + Cy. In animals under Mge + Cy, there were no differences in NaU and HW compared to controls. The results indicate a relation between Cy-related hypertension and Mg status: Mg deficiency seems to enhance the hypertensive effect of Cy via sodium retention.

Real Cause of High Level of Urinary β2-Microglobulin after Renal Transplantation

Dr. Jürgen Steinhoff, Klinik für Innere Medizin, Medizinische Universität zu Lübeck, Ratzeburger Allee 160, D-23538 Lübeck (FRG) Dear Sir, In their article “What is the true cause of high level urinary ß2-microglobulin after renal transplantation’, Nishi et al. [8] did not mention cytomegalovirus (CMV) infection as a reason for urinary ß2-microglobulin (U-ß2-MG) excretion. As reported by Bäckman et al. [1], CMV infections are known to cause high serum levels of ß2-MG. Because this protein has a low molecular weight (11.7 kD), it should be found in the urine during CMV infections. In order to test this hypothesis, we performed a prospective study in 149 patients undergoing kidney transplantation (table 1). In these patients, we determined ß2-MG, im-munoglobulin G (IgG), transferrin (Tf), albumin (Alb), C-reactive protein (CRP) and α‚-MG in 24-hour urine using a highly sensitive immunoluminometric assay [9]. In all CMV infections (n = 42), an isolated U-ß2-MG excretion was detected [4], while in all rejections, a nonselective glomerular pro-teinuria associated with urinary CRP excretion was observed [3, 6]. In ciclosporin-in-duced nephrotoxicity (n = 10), αpmicroglo-bulinuria was a characteristic feature [5]. We did not detect U-ß2-MG in rejections and cyclosporin nephrotoxicity constantly. U-ß2-MG cannot be accepted as a marker of rejection or tubulotoxicity. This protein is not de-tectabel in the urine constantly under these conditions probably because it is not stable in 24-hour urine. The reason why U-ß2-MG is, indeed, measureable in CMV infection constantly is not known. However, ß2-MG may coat CMV [2] and may become stable and detectable by this mechanism. As demonstrated, detection of isolated U-ß2-MG in 24-hour urine allows to diagnose CMV infections after renal transplantation. What Nishi et al. Í81 described as an unknown Table 1. Changes in the concentration of urinary proteins in patients after renal transplantation with cytomegalovirus infections, rejections or acute ciclosporin nephrotoxicity

β2-Microglobulinuria as an early sign of cytomegalovirus infection following renal transplantation

The frequency of cytomegalovirus infection was studied in a prospective study of 106 kidney recipients. The detection of cytomegalovirus-immediate-early-antigen and cytomegalovirus-immunoglobulin (IgM) antibodies in serum was used as the reference method and showed that 23.6% (25/106) of all patients were infected. In addition, four urinary proteins (IgG and transferrin as glomerular markers and α1-microglobulin and β2-microglobulin as tubular markers) were quantitatively measured in 24-h urine samples from all of the patients using an immunoluminometric assay (ILMA). In all cytomegalovirus infection cases a pronounced but isolated increase of urinary β2-microglobulin excretion was observed. In 20 of 25 infected patients, the p2-microglo-bulinuria occurred 1–21 days (median 5.0) earlier than the appearance of the cytomegalovirus-immediate-early-antigen in blood. Thus, it can be seen that the quantitative measurement of β2-microglobulin in urine is useful for the early detection of cytomegalovirus infection following renal transplantation.