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Biomedical subjects

J Steinhoff

Publications and source records attributed to J Steinhoff.

At least 37 records · Page 2Linked to original sources
PubMed1997

Renal graft rejection or urinary tract infection? The value of myeloperoxidase, C-reactive protein, and alpha2-macroglobulin in the urine.

Previous investigations have shown that the determination of two acute-phase proteins in the urine, C-reactive protein (CRPu) and alpha2-macroglobulin (alpha2-MGu), allows a noninvasive diagnosis of acute renal graft dysfunction. A reliable differentiation between rejection and urinary tract infection can be made only when considering the C-reactive protein in serum and urine at the same time (CRPs:CRPu ratio). Therefore, a diagnostic procedure independent of parameters other than urinary proteins is needed. As granulocytes play only a minor role in graft rejection but are a common feature in urinary tract infection, we determined a marker of granulocytes (myeloperoxidase) in urine (MPOu). Eighty-nine renal transplant recipients were included in the study. In normal courses, CRPu, alpha2-MGu, and MPOu were within the normal range. In 15 cases of acute interstitial rejection, an increased excretion of CRPu and alpha2-MGu could be confirmed, but MPOu could not be detected. On the occasion of acute vascular rejection (n=6), with the exception of one case, MPOu could not be observed. The pattern of the three urinary proteins differed in urinary tract infections (n=40): MPOu could be detected in all cases, CRPu in 50% of cases, and alpha2-MGu in 73% of cases. In patients with cytomegalovirus infection (n=7), no MPOu, CRPu, or alpha2-MGu was found. In conclusion, the simultaneous measurement of the three proteins allows a complete, noninvasive, differential diagnostic procedure of renal graft dysfunction.

Biomarkers↗
PubMed1997

[The significance of risk-adapted antiviral prophylaxis and modern virus diagnosis for organ survival after kidney transplantation].

BASIC PROBLEM AND OBJECTIVE: Viral, especially cytomegalovirus (CMV), infections are after rejection reaction the most serious problem following organ transplantation. The risk of disease correlates with the CMV donor/recipient constellation and the degree of immunosuppression. The importance of antiviral prophylaxis remains unresolved. Whether drug prophylaxis adapted to the individual risk is of clinical value was investigated in a prospective study. PATIENTS AND METHODS: A risk-adapted stepwise antiviral prophylactic regimen was given to 62 patients with renal transplants. All patients at risk of CMV infection were given acyclovir, 200 mg four times daily for 3 months. Patients with rejection reaction for which they were receiving i.v. immunosuppressive treatment additionally received CMV hyperimmunoglobulin (2 ml/kg body weight on days 1 and 14). High-risk patients (donor CMV positive and recipient CMV negative) were given as basic prophylaxis CMV hyperimmunoglobulin i.v. on days 1 and 14 after transplantation, and additionally i.v. ganciclovir during any rejection treatment. The results were compared with those of a retrospectively selected patient cohort (n = 52) who had received only acyclovir as basic prophylaxis. The diagnosis of CMV infection was made by demonstrating CMVpp65 antigen in blood. In the prospectively studied patients measurement of beta 2 microglobulin concentration was used to determine viruria in 24-hour urine. RESULTS: Among the high-risk group (donor CMV positive/recipient CMV negative) the additional prophylactic regimen significantly reduced the proportion of CMV-associated cases of rejection (14% compared with 42%, P < 0.05) in the basic prophylaxis only group. Similar results were obtained for CMV-caused transplant loss within the first 3 years (19% vs 50%, P < 0.05). The additional prophylaxis had no influence on the incidence of CMV infection. In case of active infection an isolated rise of beta 2-microglobulin in urine occurred in active infection at a mean of 6 days before CMVpp65 antigenaemia (sensitivity of 89%). CONCLUSIONS: These results indicate that risk-adapted antiviral prophylaxis can decisively influence the long-term prognosis for a renal transplant, but not the incidence of CMV infection. The early and reliable diagnosis of active CMV infection is made possible by the combined use of beta 2-microglobulinuria and pp65 antigenaemia.

Acyclovir↗
PubMed1996

Preoperative application of glucocorticosteroids efficaciously reduces the primary immunological response in kidney transplantation.

Early acute rejection episodes have a considerable influence on long-term prognosis of renal transplants. Therefore the aim of primary immunosuppressive therapy must be effective suppression of the immunological response following antigen recognition. Owing to their pharmacological properties, intravenously given glucocorticosteroids are suitable for the alteration of the primary immunological response. However, even after intravenous administration, glucocorticosteroids have a latency of hours prior to reaching maximum activity. In a prospective clinical study, 111 patients undergoing renal transplantation were preoperatively treated with 500 mg methylprednisolone for immunosuppressive induction. A historical group of 40 patients who had received the same dose as intraoperative bolus, was used for comparison. Postoperative immunosuppression did not substantially differ between the two groups. The incidence of acute rejections within 30 d after transplantation was a clinical parameter of the study. The mitogenic cytokine induction was measured in blood samples which were collected intraoperatively and on days 1, 2, and 5 after transplantation. Cytokine release served as an in vitro parameter for the immunological responsiveness of the transplant recipient. In the group under study, the incidence of acute rejections was 21% (23/111) and, in contrast, 43% (17/30) in the historical group (p < 0.05). 89% of the patients in the group being studied showed normal renal function after 1 yr, compared to 78% in the reference group (n.s.). Following preoperative (mean 5.09 h) administration of glucocorticosteroids, mitogenic cytokine induction (IL-1 beta, IL-2, sIL-2R and IFN-gamma) was almost completely blocked at the time of transplantation. A prospective, randomized study has just been started to evaluate the effect of preoperative administered glucocorticosteroids on the incidence of acute rejections and long-term allograft survival.

Adult↗
PubMed1995

[Differential diagnosis of rejection after kidney transplantation. Noninvasive rapid diagnosis by determining special urinary proteins].

Thanks to the use of highly sensitive assays for specific proteins in the urine, it is now possible to obtain, non-invasively and reproducibly, relevant differential diagnostic information when rejection is suspected following renal transplantation. The determination of C-reactive protein and alpha-2 macroglobulin, for example, makes it possible to decide whether a bacterial infection is present or not. Certain constellations of other proteins in the urine permit conclusions to be drawn, for example, as to the presence of CMV infection, the nature of the rejection, transplant glomerulopathy or cyclosporine toxicity. Follow-up studies with the aim of checking the success of treatment, are possible.

C-Reactive Protein↗
PubMed1995

Coincidence of Epstein-Barr virus reactivation, cytomegalovirus infection, and rejection episodes in renal transplant recipients.

Reactivation of the Epstein-Barr virus was reported to occur frequently under immunosuppressive therapy following organ transplantation. However, little is known about the clinical significance of these EBV reactivations. Therefore, we searched for correlations among the treatment with various immunosuppressive drugs, the incidence of CMV infections, rejection crises, and serological signs of EBV reactivation. EBV-specific antibodies were measured with novel ELISAs, utilizing the recombinant antigens p72 (for anti-EBV nuclear antigen [EBNA]1-IgG), p54, and p138 (anti-early antigen [EA]-IgM, -IgG, -IgA) in a follow-up study of 79 renal transplant recipients. Patients receiving antithymocyte globulin or antilymphocyte globulin therapy showed increasing anti-EA-IgG and -IgA more often than did patients not receiving antithymocyte globulin or antilymphocyte globulin therapy (P < 0.05). In patients receiving OKT3 antirejection therapy, anti-EA-IgM seroconversion was found more frequently (P < 0.01). A significant correlation was also found between groups of patients who had had at least one rejection episode versus patients without any sign of organ rejection, and the incidence of increasing anti-EA-IgG (P < 0.05). Since in most of these patients signs of EBV reactivation followed the appearance of the rejection episode, this may not be due to viral-induced rejection but may be caused by the reinforced immunosuppression during antirejection therapy. As opposed to patients with no signs of CMV infection and with nonsymptomatic CMV infection, patients undergoing symptomatic CMV infection showed anti-EA-IgM seroconversion (P < 0.01), increasing anti-EA-IgA (P < 0.01), and decreasing anti-EBNA-IgG (P < 0.01) more frequently. Our results confirm the role of immunosuppressive therapy in the pathogenesis of EBV reactivation. We further demonstrate a striking coincidence of EBV reactivation and symptomatic CMV infection.

Antibodies, Viral↗
PubMed1995

[The von Hippel-Lindau syndrome. Its differential diagnosis from cystic kidneys in adulthood].

A 51-year-old patient with severe back pain had undergone resection of a benign cerebellar tumour when aged 15 years. In addition, polycystic kidney disease was diagnosed 24 years ago, bilateral phaeochromocytoma 2 years ago, and for 4 months before the present admission he had been on haemodialysis. The family history indicated autosomal dominant inheritance of the polycystic renal disease. His general condition was found to have deteriorated, he had pain on pressure over the upper thoracic and lower lumbar vertebrae, and the kidneys were enlarged on palpation. There were increased concentrations of calcium (3.01 mmol/l), parathormone (2.0 ng/l), carcinoembryonic antigen (13.5 micrograms/l) and TPA (69 U/l). Computed tomography demonstrated cystic and solid parts of much enlarged kidneys. Biopsy revealed a poorly differentiated clear-cell renal carcinoma. Further information concerning the previously removed brain tumour showed this to have been an haemangioblastoma of the cerebellar tonsils indicating the diagnosis of v. Hippel-Lindau disease. Nine other family members had been affected, but none had the full-blown picture of the disease. The patient died 3 weeks later from the rapidly advancing tumour. Autopsy showed the bilateral renal carcinoma, bilateral phaeochromocytoma and metastases to the sternum, femurs, vertebrae and liver.

Adrenal Gland Neoplasms↗
PubMed1995

[Intestinal vasculitis and glomerulonephritis in hepatitis C- associated cryoglobulinemia].

In a 53-year-old female patient with recurrent, sometimes bloody diarrhea, the long standing diagnosis of an ANA-negative lupus erythematosus with membranoproliferative glomerulonephritis, leucocytoclastic vasculitis and chronic hepatitis was ruled out and the diagnosis of a hepatitis C associated cryoglobulinaemia was established. The origin of the diarrhea was due to intestinal vasculitis as a result of cold food or beverages.

Cryoglobulinemia↗
PubMed1994

[alpha 2-macroglobulin in urine. Significance for differential diagnosis of rejection and infections after kidney transplantation].

The value of measuring the urinary concentration of alpha 2-macroglobulin in addition to that of C-reactive protein (CRP) was assessed in a prospective study of 78 consecutive patients (29 women, 49 men; mean age 48.7 [19-75] years) after renal transplantation. alpha 2-Macroglobulin was never demonstrated in urine when the course was normal (n = 38), cytomegalovirus infection had occurred (n = 26) or acute cyclosporin nephrotoxicity (n = 5) or glomerular disease in the transplant (n = 10). CRP was present in only a few such cases. Interstitial rejections (n = 26) always led to urinary alpha 2-macroglobulin and CRP excretion without haematuria, while in vascular rejection (n = 3) the haemoglobin test was also positive. Urinary infection (n = 20) and urosepticaemia (n = 6) always brought about the urinary excretion of alpha 2-macroglobulin and CRP, as well as a usually highly positive haemoglobin test. alpha 2-Macroglobulin was absent but CRP always present in extrarenal bacterial infections (n = 30). Postrenal blood admixture was always characterized by a positive haemoglobin test and alpha 2-macroglobulin in urine, while in most cases (83%) CRP was absent. --These results indicate that the constellation "alpha 2-macroglobulin negative/CRP positive" is a pathognomonic for extrarenal bacterial infection (sensitivity 100%, specificity 98.9%). The presence of alpha 2-macroglobulin alone makes postrenal blood admixture probable. If both proteins are present in the urine, rejection and urogenital bacterial infection must be excluded by further tests.

Adult↗
PubMed1993

A longitudinal prospective study of cytomegalovirus pp65 antigenemia in renal transplant recipients.

Cytomegalovirus (CMV)-encoded pp65 antigen in peripheral blood leukocytes (CMV antigenemia) was investigated in 1017 serial samples from 64 patients for 16 weeks after renal transplantation in a prospective study. In 110 samples from 24 patients, at least one antigen-positive leukocyte was identified. The median number of stained cells was 4 (range 1-1000) per 4 x 10(5) leukocytes. Twenty-one of 24 patients with serological signs of an active CMV infection were antigen-positive (sensitivity 87.5%), whereas 3 patients with antigenemia did not show serological signs of infection during the observation period (specificity 92.5%). Positive results were obtained 19 days (median) before serological response and 9 days (median) before the onset of CMV syndrome. The sensitivity in defining a CMV syndrome was 100% (n = 8). In all patients who presented with CMV syndrome, antigenemia was present prior to the onset of symptoms or on the same day. In contrast, serological monitoring rendered the diagnosis of CMV infection possible at the onset of clinical symptoms in only two of eight patients. We conclude that (1) insufficient results obtained with the CMV antigenemia assay by other investigators are mainly due to technical problems that can easily be overcome by the protocol presented and (2) the detection of CMV pp65 antigen in peripheral blood leukocytes is an excellent tool for rapid and early diagnosis of CMV infection.

Antibodies, Viral↗
PubMed1993

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) supplies further information in this regard, we compared both methods. In 41 renal transplant patients the PCR assay yielded a sensitivity of 100% compared with 87.5% of the antigenemia assay. Specificities reached 67% and 92.5%, respectively. In 5 patients without both serological signs of infection and antigenemia, CMV DNA was also found. The duration of CMV DNA detection in PBL during active infection was significantly longer than antigenemia. Even after successful treatment of symptomatic CMV disease, DNA was present for a period of weeks without any relapse of disease. In contrast, antigenemia disappeared after antiviral therapy and reappeared only in one patient with relapse of CMV disease. We conclude that PCR offers no advantages over antigen detection in monitoring for CMV infections after renal transplantation.

Base Sequence↗
PubMed1993

The effects of lansoprazole, 30 or 60 mg daily, on intragastric pH and on endocrine function in healthy volunteers.

Seven days of dosing with either 30 mg or 60 mg of lansoprazole were compared with placebo in a double-blind, randomized, three-way cross-over study in 12 male healthy volunteers. Twenty-four-hour intragastric pH was measured after 7 days of dosing with each regimen, as well as 3 and 7 days after the end of dosing. During dosing with placebo, intragastric pH was above 4 for a median of 51 minutes. pH values were significantly raised to above 4 for 8.45 and 8.33 hours on Day 7 of dosing with lansoprazole 30 and 60 mg, respectively, but returned to normal by the third day after stopping dosing. No clinically relevant influence on endocrine function (serum concentrations of insulin, aldosterone, testosterone, parathormone, glucagon, T3, T4, TSH, LH, FSH, STH, prolactin, circadian cortisol profile, ACTH test) was observed. No serious adverse clinical or laboratory events were noted.

2-Pyridinylmethylsulfinylbenzimidazoles↗