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Biomedical subjects

T F Müller

Publications and source records attributed to T F Müller.

18 recordsLinked to original sources

Effect of maternal immunity on the immune response to oral vaccination against rabies in young foxes.

OBJECTIVE: To determine effect of maternal antibodies on immune response to oral vaccination against rabies in young foxes. ANIMALS: 250 cubs from 48 vixens. PROCEDURE: Sera were obtained from cubs of 36 vaccinated (maternally vaccinated [MV+]) and 12 nonvaccinated (MV-) vixens between 23 and 71 days of age and tested for neutralizing antibodies. Seventy-one MV+ cubs and 33 MV-cubs were vaccinated orally with modified-live virus vaccine SAD B19. Geometric mean titer (GMT) was determined in these cubs approximately 21, 39, and 57 days after vaccination. In a subsequent experiment, 10 vaccinated MV+ cubs, 6 vaccinated MV- cubs, and 6 control cubs were challenge inoculated with virulent rabies virus approximately 100 days after vaccination. RESULTS: Serum GMT of nonvaccinated MV cubs (0.23 U/ml) was significantly greater than that of non-vaccinated MV- cubs (0.15 U/ml). The GMT of vaccinated MV+ cubs 21, 39, and 57 days after vaccination were 2.85, 2.11, and 0.79 U/ml, respectively, and were significantly less than those of vaccinated MV- cubs (12.19, 6.76, and 4.02 U/ml, respectively). All challenge-inoculated cubs with GMT < 0.5 U/ml succumbed to rabies. CONCLUSION AND CLINICAL RELEVANCE: Partially impaired immune response in cubs < 8 weeks old from vaccinated vixens causes insufficient protection against rabies. Inhibition of the immune response persists longer than the period during which maternal antibodies are detectable. Thus, oral vaccination campaigns for young foxes in areas where vaccination has been performed need to be reconsidered.

Administration, Oral↗

Experimental infection of European wild boars and domestic pigs with pseudorabies viruses with differing virulence.

OBJECTIVE: To determine susceptibility of European wild boars (Sus scrofa) to infection with pseudorabies virus (PrV) and to characterize the virulence of a wildboar PrV isolate for wild and domestic pigs. ANIMALS: 18 wild boars and 16 domestic pigs. PROCEDURE: Three groups of 4 wild boars were inoculated with PrV Bartha, Kaplan, and a wild-boar isolate (BFW1) and housed with uninfected pigs. Two groups of domestic pigs (4 and 8 pigs/group, respectively) were inoculated with various doses of BFW1. Animals were observed daily for clinical signs, and samples were tested for PrV excretion and homologous antibodies. After reactivation of latent infection by induced immunosuppression, PrV was detected in tissues of necropsied animals, using cell culture and a polymerase chain reaction (PCR). RESULTS: Clinical signs depended on virulence of the PrV strain and dose of inoculum. Only infection with PrV Kaplan resulted in severe disease and death. Virus was isolated from nasal and genital swab specimens. Antibodies were first detected on day 7 after inoculation; a specific humoral immune response was delayed in BFW1-infected animals. Virus was isolated from various tissues of Kaplan-infected wild boars, whereas mainly viral DNA was detected in a few tissues of Bartha- and BFW1-infected animals, using PCR after immunosuppression. CONCLUSIONS AND CLINICAL RELEVANCE: European wild boars are susceptible to transmission of PrV infection from domestic pigs and vice-versa. The PrV isolate BFW1 is of low virulence and seems to be adapted to the wild boar population from which it was isolated.

Animals↗

Immediate and long-term results of ATG induction therapy for delayed graft function compared to conventional therapy for immediate graft function.

The use of polyclonal antibodies for delayed graft function (DGF) was tested in 83 renal allograft recipients. Conventional immunosuppression (CI) was given to 52 patients with immediate graft function (IGF) while 31 patients with DGF received the polyclonal antibody ATG. Administration of OKT3 was restricted to steroid-resistant acute rejections in both groups. The incidence and severity of acute rejections, graft survival rate, CMV infections, and lymphocyte subsets were examined. ATG patients experienced a total of 0.6 acute rejections per patient, whereas CI patients had 0.9 on the average (P < 0.05). Second and third acute rejections occurred less frequently and later in the ATG group than in the CI group (P < 0.01). Steroid-resistant acute rejections occurred in 20 of the CI patients (38 %) but in only 7 of ATG patients (23 %). One-year graft survival in the CI and ATG groups was 98.1% and 93.2%, respectively. A decreased CD4 + to CD8 + T-lymphocyte ratio of about 0.5 was still detectable 5 years after the initial ATG administration. Hence, patients with DGF appear to benefit from induction therapy with ATG.

Adult↗

[Intrarenal doppler flow analysis in patients with kidney transplantation and stable transplant function].

AIM OF THE STUDY: Intrarenal arterial Doppler sonography is used in noninvasive monitoring of transplant kidneys with controversial results. With the application of the method on renal transplants with stable function normal values should be generated and pitfalls should be identified. METHOD AND STUDY SUBJECTS: In a prospective study doppler findings in 61 renal transplant patients with stable graft function were compared with measurements in native kidneys of 60 healthy controls. In all kidneys duplex Doppler studies of arcuate/interlobar intrarenal arteries were performed and both the resistance index (RI) as well as the pulsatility index (PI) was determined. RESULTS: The results of our study are summarized: 1. Transplanted kidneys have significantly higher intrarenal arterial flow indices in comparison to native kidneys: RI = 67 +/- 5% in allografts vs. RI = 57 +/- 5% in native kidneys; and PI = 123 +/- 21% in allografts vs. PI = 91 +/- 15% in native kidneys, respectively. 2. RI and PI increase with age in both the native kidneys and the allografts. However, the increase in the transplanted kidney correlates with the age of the recipient but not with the age of the donor. 3. Corresponding to the increase in RI and PI the blood pressure is significantly elevated in the elderly. 4. The degree of external pressure with the transducer on the graft has an impact on the intrarenal arterial Doppler findings and measurements obtained. CONCLUSION: The intrarenal arterial Doppler findings dependent on various extrarenal factors. Using arterial Doppler sonography to evaluate transplant kidneys it is mandatory to take into account factors such as recipient's age and hemodynamic situation. External pressure with the transducer on the graft must be avoided. Once these factors were considered the intrarenal arterial Doppler sonography of kidney transplant is a valuable diagnostic tool.

Adult↗

Noninvasive monitoring using serum amyloid A and serum neopterin in cardiac transplantation.

The monitoring of allograft function for cardiac transplant patients still relies on endomyocardial routine biopsies. We investigated the diagnostic value of noninvasive monitoring using the parameters serum amyloid A protein and serum neopterin. The circulating levels of the acute phase reactant, amyloid A protein, and the macrophage product, neopterin, were measured serially in 13 patients after cardiac transplantation. The mean period of observation was 240 days. Nine acute cardiac allograft rejections, five cases of viral infection and eight cases of bacterial infection occurred. The levels of serum amyloid A protein and serum neopterin remained low (x = 6.0 mg/dL and 12.6 nmol/L, respectively) during the periods of stable graft function. In contrast, both parameters were significantly elevated (p < 0.01) during the rejection episodes (x = 12.7 mg/dL and 38.0 nmol/L for serum amyloid A protein and serum neopterin, respectively). For a reliable differentiation between rejection and stable graft function, serum amyloid A protein had a diagnostic accuracy of 84% (with a cut-off level of 10 mg/dL) and serum neopterin had one of 75% (with a cut-off level of 23 nmol/L). However, significant increases in the circulating levels of serum amyloid A protein and serum neopterin were also observed during bacterial (x = 14.9 and 88 nmol/L, respectively) and viral (x = 6.2 mg/dL and 44 nmol/L, respectively) infections. The detection of immunological complications after cardiac transplantation using serial measurements of serum amyloid A protein and serum neopterin is possible. These parameters can be used to help in judging both the need and the optimal timing for the otherwise frequent endomyocardial biopsies.

Antilymphocyte Serum↗

Biocompatibility differences with respect to the dialyzer sterilization method.

The impact of the method of sterilization (steam vs. ethylene oxide, ETO) on indices of biocompatibility is investigated using polysulfone membranes. Eight patients were treated with a random choice of the high-flux membranes F60S (steam) and F60 (ETO) and the low-flux membrane F6 (ETO). Blood samples were taken prior to and 5, 15, 30, 60, and 180 min after the start of hemodialysis. White blood cell count, platelet count, and plasma concentrations of polymorphonuclear neutrophil elastase, complements C3a and C5a, and beta2-microglobulin were determined. The dialysis procedure was associated with a significant decrease in white blood cell count and beta2-microglobulin level and a significant increase in polymorphonuclear neutrophil elastase and complement C3a and C5a levels. However, the steam-sterilized F60S membrane had a significantly lower impact on the biocompatibility indices than the ETO-sterilized F60 and F6 membranes (p < 0.05 or p < 0.001 for the individual markers). We conclude that using steam instead of ETO for sterilization may improve the biocompatibility of membranes.

Adult↗

Persistent long-term changes in lymphocyte subsets induced by polyclonal antibodies.

BACKGROUND: Clinicians are well aware of the short-term effects of immunosuppression by mono- or polyclonal antibodies. Little is known about long-term changes induced by these therapies. METHODS: Forty-three renal allograft recipients were selected according to their initial postoperative immunosuppression: (1) BI group=basic immunosuppression with steroids and cyclosporine, n=16; (2) ATG group=basic immunosuppression plus polyclonal antibody antithymocyte globulin (ATG), n=11; and (3) OKT3 group=basic immunosuppression plus monoclonal antibody OKT3, n=16 patients. At intervals of 6 months, the following parameters were measured prospectively: lymphocyte surface antigens (HLA-DR, CD3, CD4, CD8, CD16, CD19, CD56, and CD57); serum and urine neopterin; serum amyloid A; and indirect and direct tests for herpes viruses. RESULTS: The mean period of observation was 58.4 months. The most significant differences between the groups occurred for CD4+ and CD8+ T cells. The ratios of CD4+ to CD8+ cells (n=278 measurements) were significantly and persistently lower in the ATG group (P<0.001, Brown-Mood test). Five years after transplantation, the ATG group had a CD4+ to CD8+ cell ratio of x=0.6 versus x=1.7 in the OKT3 group and x=2.0 in the BI group. This inversion was due to a persistent depletion of the CD4+ cells and an increased regeneration of the CD8+ cells, in particular of the CD8+brightCD57+ subpopulation. Extent and duration of CD4+ depletion correlated with the cumulative ATG dose (r=0.7, P<0.05, Spearman rank correlation test). CONCLUSION: Therapy with polyclonal antibody ATG induces dose-dependent long-term changes in T-cell lymphocyte subsets, which persist over a period of years.

Adult↗

Pancreas-specific protein (PASP), serum amyloid A (SAA), and neopterin (NEOP) in the diagnosis of rejection after simultaneous pancreas and kidney transplantation.

A reliable, noninvasive indicator of pancreatic allograft rejection is urgently needed. In this study, serum (S), plasma (P), and urine (U) levels of pancreas-specific protein (P-PASP, U-PASP), neopterin (S-NEOP, U-NEOP), amylase (U-AMYL), and amyloid A (SAA) were measured daily in ten type I diabetic patients following simultaneous pancreas and kidney transplantation (SPK). Rejection episodes occurred in three isolated pancreas, nine isolated kidney, and five simultaneous pancreas and kidney transplants. In the case of the eight pancreas rejections, SAA was the rejection marker with the highest diagnostic accuracy (94%). Using P-PASP and U-PASP, an accuracy of 81% and 79%, respectively, was achieved. During viral infections, U-NEOP levels increased to a maximum level of 1904 mumol/mol creatinine, whereas during bacterial infections, SAA levels increased to a maximum value of 43 mg/dl. SAA, measured for the first time in SPK, appears to be a valuable rejection parameter. In combination with U-NEOP and U-AMYL, a differential diagnosis between rejection, bacterial infection, and viral infection was possible. Neither U-PASP nor P-PASP monitoring led to a significant improvement in the results.

Acute Disease↗

Detection of renal allograft rejection by complement components C5A and TCC in plasma and urine.

Allograft rejection is associated with complement activation. Yet inconsistent results were obtained in evaluating plasma levels of complement factors or activation products as rejection markers. Therefore the human anaphylatoxin C5a and the soluble terminal complement complex (TCC) were measured by daily enzyme immunoassays on plasma (P) and urine (U) samples from 28 patients undergoing renal transplantation over a mean postoperative period of 25.8 days. The complement levels were evaluated longitudinally (cutoff of 100% increase on the previous day's level) during periods of rejection, stable graft function, acute tubular necrosis, and cytomegalovirus disease. Regarding the detection of 13 acute rejection episodes, U-C5a showed a diagnostic accuracy of 81% (sensitivity of 85%, specificity of 77%), P-C5a one of 62%, and P-TCC one of only 30%. The U-C5a increment (mean rise of 379%) preceded the clinical diagnosis of rejection by an average of 1.6 days. Cytomegalovirus diseases (n = 4) were associated with high P-C5a levels (mean increase of 251% by the time of the first detection of viral DNA). In contrast, resumption of kidney function after acute tubular necrosis (n = 10 periods) was heralded by marked peaks of U-C5a (x = 43.7 microg/l). U-TCC was not detected in any clinical setting. In conclusion, as opposed to P-TCC, U-TCC, and P-C5a, the anaphylatoxin C5a, measured daily in urine, might have potential as an early and reliable marker for acute renal allograft rejection.

Adult↗

The anaphylatoxin C5a, a new parameter in the diagnosis of renal allograft rejection.

In the underlying study the diagnostic value of the anaphylatoxin C5a was evaluated in kidney transplantation. In 49 transplant patients the following parameters were measured daily for a mean period of 25.1 days: plasma C5a [P-C5a], urine C5a [U-C5a], serum amyloid A [SAA], serum neopterin [S-NEOP] and urine neopterin [U-NEOP]. Sensitivity, specificity and day of first significant parameter increase (exceeding a cut-off level of > 50%) were evaluated retrospectively during 30 periods of rejection and 30 periods of stable graft function. U-C5a was the parameter with the highest sensitivity (84%) and specificity (84%), increasing in the mean 1.3 days before clinical diagnosis of rejection. Sensitivity and specificity of the other markers was lower: SAA 77% and 77%, U-NEOP 68% and 65%, S-NEOP 45% and 77%, and P-C5a 45% and 48%, respectively. During four instances of cytomegalovirus disease extremely high U-NEOP (> or = 1520 +/- 518 mumol/mol creatinine) and slightly increased P-C5a levels (> or = 1.5 +/- 1.4 ng/ml) occurred. Elevated urinary excretion of C5a seems to be a reliable and early marker of renal allograft rejection. In combination with SAA and U-NEOP, the daily assessment of U-C5a differentiates between viral infection and allograft rejection.

Adult↗

The influence of the immunosuppressants OKT3 and ATG on immunological parameters.

Cytokines play an important role in the immune response induced by organ grafting, particularly during episodes of rejection. We tested the influence of monoclonal and polyclonal antibodies upon levels of mediators of the immune system. In 29 patients various cytokines and mediators were serially analyzed following transplantation. Thirteen patients received polyclonal antibodies (ATG) and 7 monoclonal (OKT3). Both OKT3 and ATG induced a rise in body temperature. Mean serum levels of amyloid A, neopterin, plasma levels of TNF alpha, interleukin 2 receptor (IL-2R) and urine levels of interleukin 6 (IL-6) and IL-2R were elevated when antibodies were employed. Interestingly, urine and plasma TNF-alpha as well as urine IL-6 and IL-2R remained elevated following ATG but not OKT3 and did not rise in case of basic treatment. In summary, antibody therapy increased levels of immune mediators. These mediators remained elevated following the discontinuation of treatment in case of ATG but not OKT3.

Acute Disease↗

Immediate metabolic effects of different nutritional regimens in critically ill medical patients.

OBJECTIVE: Metabolic effects of different caloric regimens were investigated in nonsurgical, medical patients with multiple-organ failure (MOF). DESIGN: Seven total parenteral nutrition (TPN) regimens were administered, differing in amount (14, 28, and 56 kcal/kg per day, i.e., hypo-, iso-, and hypercaloric nutrition, respectively) and distribution [carbohydrates (COH), amino acids (AA), long-chain and medium-chain triglycerides (LCT/MCT)] of calories. Each regimen was administered over 12 h. Metabolism was monitored by energy expenditure (EE), body temperature (BT), protein breakdown (PB), and blood glucose and serum lactate levels. Measurements were started within 2 days of MOF onset. SETTING: The study was conducted in a medical intensive care unit. PATIENTS: Twenty patients with MOF on mechanical ventilation (mean Apache II score x = 26) were investigated. MEASUREMENTS AND RESULTS: The mean values of the EE (x = 31 kcal/kg per day), BT (x = 38 degrees C), PB (x = 1.5 g/kg per day), and lactate (x = 2.0 mmol/l) and glucose level (x = 222 mg/dl) parameters were elevated. EE, BT, and lactate and glucose levels were significantly lower under hypocaloric nutrition than during iso- and hypercaloric nutrition (p < 0.01). Differences in the metabolic effects of LCT and MCT were not significant. PB was significantly elevated under hypercaloric nutrition (p < 0.01). Protein balance was positive under hypercaloric nutrition, and negative under iso- and hypocaloric nutrition. CONCLUSIONS: In nonsurgical, medical patients neither hypercaloric nor isocaloric nutritional support prevented protein catabolism; in contrast, they enhanced the metabolic burden measured by EE, thermogenesis, urea production rate, and glucose and lactate levels. A hypocaloric regimen is therefore recommended for these patients during the early phase of MOF.

Aged↗

Metoclopramide (Primperan) in the treatment of ureterolithiasis. A prospective double-blind study of metoclopramide compared with morphatropin on ureteral colic.

A prospective double-blind study was performed to compare metoclopramide (Primperan) with morphatropin in the treatment of ureteral colic. Twenty-one patients (10 in the morphatropin group and 11 in the metoclopramide group) entered the study and diagnosis was confirmed radiologically. Using the Mann-Whitney rank sum test, no significant difference was found in the pain-relieving effect 10, 20, or 30 min after treatment with either 1 ml morphatropin s.c. or 20 mg metoclopramide i.v. Two patients in the morphatropin group developed nausea and giddiness, respectively, and 1 patient from this group was omitted due to the development of urticaria. No side effects occurred in the metoclopramide group. Thus metoclopramide seems to be an alternative to the traditional treatment of ureteral colic with morphia.

Acute Disease↗