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Biomedical subjects

M Zeier

Publications and source records attributed to M Zeier.

At least 19 recordsLinked to original sources

[Renal replacement therapy in the intensive care unit].

Acute renal failure in critically ill patients in the intensive care unit is associated with high morbidity and mortality which is independent of the underlying etiology. Despite improvements in intensive care medicine and renal replacement therapy, patients with acute renal failure have much higher morbidity and mortality rates than patients without acute renal failure in the intensive care unit. In this overview, we summarize the literature on the incidence and mortality of patients with acute renal failure in the intensive care unit. Furthermore, we discuss timing of the initiation of renal replacement therapy, patient outcome with different renal replacement therapies and the adequate dialysis dose to be delivered.

Acute Kidney Injury↗

Desensitization strategies enabling successful renal transplantation in highly sensitized patients.

Currently, the number of highly sensitized patients awaiting a renal transplant is increasing on the waiting lists of different organ exchange organizations. Due to the presence of antibodies against a broad variety of human leukocyte antigen (HLA) specificities, highly sensitized patients have a markedly reduced chance of receiving a crossmatch-negative organ. It has long been recognized that hyperacute rejection is associated with the presence of donor-specific anti-HLA antibodies at the time of transplantation. Meanwhile treatment protocols have been developed to achieve successful transplantation across antibody barriers. Therefore, the presence of donor-specific anti-HLA antibodies and a positive serological crossmatch are no longer considered as an absolute contraindication to renal transplantation. Mainly, two desensitization protocols have been established in order to overcome a positive crossmatch or to enhance the chance of highly sensitized patients to receive a crossmatch-negative organ: high-dose intravenous immunoglobulin (IVIg) or low-dose IVIg in combination with plasmapheresis. Herein, we summarize the characteristics of these two treatment regimes along with other alternative approaches that are currently used for the management of kidney graft recipients with broad alloantibody reactivity against potential kidney donors.

Desensitization, Immunologic↗

The role and value of sirolimus administration in kidney and liver transplantation.

Enormous advancements in visceral transplantation have led to significant improvements in the quality of life of patients. However, despite these developments, the average graft half-life after transplantation has remained almost unchanged and chronic rejection is still considered a major problem. In this regard, more concerns have shifted to factors influencing long-term graft survival, patient survival, and quality of life. To achieve this goal, detrimental effects of immunosuppressive (IS) agents, which have deleterious influence on the quality of life and/or patient survival, should be reduced. In the course of recent years, the transplant community has worked on reducing these side effects by developing new ISs, employing new combination regimens, or finding and adjusting optimal dosages and blood level concentrations. Among the IS agents, the antifungal, antitumoral and IS activity of mammalian target of rapamycin (mTOR) inhibitors without nephrotoxicity, have received special attention regarding this new class of IS. Sirolimus (SRL), as the first member of mTOR inhibitors, has been utilized in many clinical trials with respect to its benefit-risk assessment. In our review, the clinical evolution of SRL, as well as the evidence-based clinical benefits of SRL in kidney and liver transplantation (KTx, LTx), are summarized. Various studies of SRL in KTx and LTx have shown that combination therapy with SRL will enrich the variety of IS modalities. It also can be regarded as a safe base therapy to which other necessary drugs can be added. In addition to the enhanced acute rejection prophylaxis, and in contrast to the calcineurin inhibitors (CNI) and steroids, this drug solely does not have common side effects such as nephrotoxicity, neurotoxicity, diabetes mellitus and hypertension. Moreover, this agent might diminish vasculopathic processes that mediate chronic allograft nephropathy (CAN). Therefore, by reducing the likelihood of CAN it can decrease the rate of long-term organ failure. One possibly desirable characteristic of SRL is its antiproliferative effect, which could provoke antitumoral or antiatherogenic activity following transplantation. Despite all promising impacts of SRL in organ transplantation, there are some concerns regarding the adverse effects of this drug, for instance dyslipidemia, pneumonitis and wound healing problems. However, the majority of these side effects can be reduced or ceased by careful dose adjustments and correct timing of use. In conclusion, after a decade of both in vivo and in vitro studies on SRL, it can be advocated that SRL is a promising, potent and effective IS agent as it reduces the rate of acute rejection episodes in de novo transplants. It could improve the quality of life, graft and patient survival rate, and achieve excellent outcomes with few adverse effects when wisely used in combination with other immunosuppressants.

Graft Rejection↗

Immunosuppressive standards in simultaneous kidney-pancreas transplantation.

Simultaneous pancreas-kidney transplantation is an established procedure for patients with type I diabetes and end-stage renal disease. Continuous advances in the operation techniques with consequent reduction of perioperative morbidity and mortality and the introduction of modern immunosuppressive agents improved not only patients but also graft survival and significantly decreased rejection episodes of both kidney and pancreas grafts. Availability of a variety of new immunosuppressants in the clinical routine and increasing experience of the transplant specialists allowed further developments of therapeutic schemes with application of induction and maintenance immunosuppressive protocols. In this article, we summarize the current status of immunosuppressive regimens in simultaneous pancreas and kidney transplantation.

Graft Rejection↗

Wound complications following kidney and liver transplantation.

Advances in surgical techniques and immunosuppression (IS) have led to an appreciable reduction in postoperative complications following transplantation. However, wound complications as probably the most common type of post-transplantation surgical complication can still limit these improved outcomes and result in prolonged hospitalization, hospital readmission, and reoperation, consequently increasing overall transplant cost. Our aim was to review the literature to delineate the evidence-based risk factors for wound complications following kidney and liver transplantation (KTx, LTx), and to present the preventive and therapeutic modalities for this bothersome morbidity. Generally, wound complications are categorized as superficial and deep wound dehiscences, perigraft fluid collections and seroma, superficial and deep wound infections, cellulitis, lymphocele and wound drainage. The results of several studies showed that the most important risk factors for wound complications are IS and obesity. Additionally, there are surgical and/or technical factors, including type of incision, reoperation, and surgeon's expertise, as well as comorbidities such as advanced age, diabetes mellitus, malnutrition, and uremia. Preventive management of wound complications necessitates defining their etiological factors so that their detrimental effects on healing processes can be addressed and reduced. IS modalities and agents, especially sirolimus (SRL), and steroids (ST) should be adjusted according to the patient's co-existing risk factors. SRL should be administered three months after transplantation and ST should be tapered as soon as possible. A body mass index (BMI) lower than 30 kg/m2 is advisable for inclusion in a transplantation program, but higher BMIs do not exclude recipients. Surgical risk factors can be prevented by applying precise surgical techniques. Therapeutic modalities must focus on the most efficient and cost-effective medications and/or interventions to facilitate and improve wound healing.

Humans↗

Real-time contrast-enhanced sonography of renal transplant recipients predicts chronic allograft nephropathy.

Real-time contrast-enhanced sonography (RT-CES) can assess microvascular tissue perfusion using gas-filled microbubbles. The study was performed to evaluate the feasibility of RT-CES in detecting chronic allograft nephropathy (CAN) in comparison to color Doppler ultrasonography (CDUS). A total of 26 consecutive renal transplant recipients were prospectively studied using RT-CES and conventional CDUS. Transplant tissue perfusion imaging was performed by low-power imaging during i.v. administration of the sonocontrast Optison. Renal tissue perfusion was assessed quantitatively using flash replenishment kinetics of microbubbles to estimate renal blood flow A *beta (A = peak signal intensity, beta= slope of signal intensity rise). In contrast to conventional CDUS resistance and pulsatility indices, renal blood flow estimated by CES was highly significant related to S-creatinine (r =-0.62, p = 0.0004). Determination of renal blood flow by CES reached a higher sensitivity (91% vs. 82%, p < 0.05), specificity (82% vs. 64%, p < 0.05) and accuracy (85% vs. 73%, p < 0.05) for the diagnosis of CAN as compared to conventional CDUS resistance indices. Perfusion parameters derived from RT-CES significantly improve the early detection of CAN compared to conventional CDUS. RT-CES using low-power real-time perfusion imaging is a feasible method to evaluate microvascular perfusion in renal allograft recipients.

Adolescent↗

Color Doppler indices of renal allografts depend on vascular stiffness of the transplant recipients.

A resistance index (RI) of 0.8 or higher was shown to be a strong predictor of kidney allograft and patient survival. Uncertainties persist since the intrarenal RI is closely associated with the vascular stiffness of the allograft recipient. To clarify the diagnostic value of RI further, we analyzed parameters of vascular stiffness of the recipient and intrarenal RI of the renal allograft. In a prospective study laboratory and clinical parameters, pulse wave velocity (PWV), intima media thickness (IMT) and RI were obtained in 76 kidney allograft patients. We found that the RI values significantly correlated with the PWV (p < 0.05) and the recipients age (p < 0.01) but not with the donor age and renal function. Using multiple regression analysis recipient age, PWV, pulse pressure (PP) and IMT were identified as independent factors influencing RI values. For a more correct interpretation of the RI values in renal allografts parameters of vascular stiffness such as IMT, PP or PWV should be included.

Adult↗

The first 5 years of the family clinic for HIV at Tygerberg Hospital: family demographics, survival of children and early impact of antiretroviral therapy.

BACKGROUND: Family clinics address the problems of HIV-infected children and their families. The aims were to document demographics of the children and caregivers attending the Family Clinic for HIV at Tygerberg Academic Hospital (TAH) and to investigate factors affecting disease progression in children. METHODS: A retrospective folder review of children and parents attending the Family Clinic at TAH between January 1997 and December 2001, a period noted for its lack of antiretroviral treatment. RESULTS: Of 432 children seen for testing, 274 children, median age 16.9 months, were HIV-infected. During follow-up, 46 children died (median age 23 months) and 113 were lost to follow-up. The majority of children were malnourished. Those <2 years of age had lower weight for age Z-scores (WAZ) than older children (p<0.001). At presentation, 47 per cent were in clinical stage B and two-thirds had moderate or severe CD4+ T cell depletion. Seventeen children had received highly active antiretroviral therapy (HAART), 12 dual and 31 monotherapy. HAART was associated with improved survival compared to dual or monotherapy. Risk of death was reduced from eleven-fold for a WAZ <-4 to four-fold between -2 and -3. There was no association with immunological and clinical classification at entry and risk of mortality. Only 18 per cent of parents were evaluated in the clinic. Non-parental care was documented for 25 per cent of families. CONCLUSIONS: A low WAZ is associated with poor survival in children. Nutritional status should receive more attention in HIV disease classification in children. Parent utilization of the clinic was inadequate. Even in the absence of HAART, extended survival in children is possible.

Age Factors↗

[Integrated skills laboratory concept for undergraduate training in internal medicine].

BACKGROUND AND OBJECTIVE: An amendment to the German medical curriculum in April 2002 will place basic practical skills at the centre of medical training. We report here on the implementation and evaluation of an obligatory, tutor-guided, and integrated skills laboratory concept in the field of internal medicine. METHODS: To test the effectiveness of a skills laboratory training on OSCE performance a pilot study was carried out. The experimental group, of 77 students, participated in seven sessions of communication training, skills laboratory training, and bedside teaching, each lasting one and a half hours. The control group of 66 students had as many sessions but was only offered bedside-teaching. The evaluation of acceptance of skills' training as well as the related increase in individual competence is on-going (summer term 2004: n = 176 students). RESULTS: The integrated skills laboratory concept was rated at 3.5 (SD = 1.2) on a 5-point scale and was acknowledged as practice-oriented (M = 4.2; SD = 1.0) and relevant for doctors' everyday lives (M = 3.6; SD = 1.1). Increased levels of competence according to individual self-evaluations proved to be highly significant (p<.001), and results of the pilot study showed that the experimental group had a significantly better OSCE performance than the control group (p<.001). CONCLUSION: This pilot study shows that curriculum changes promoting basic clinical skills are effective and lead to an improved practical education of tomorrow's physicians. The integrated skills laboratory concept is well accepted and leads to a relevant increase in competence in the practice of internal medical. The presented skills laboratory concept in internal medicine is proving to be a viable and efficient learning tool.

Adult↗

Angular distributions for (3,4)(Lambda)H bound states in the (3,4)He(e,e(')K+) reaction.

The (3,4)(Lambda)H and (4)(Lambda)H hypernuclear bound states have been observed for the first time in kaon electroproduction on (3,4)He targets. The production cross sections have been determined at Q(2)=0.35 GeV2 and W=1.91 GeV. For either hypernucleus the nuclear form factor is determined by comparing the angular distribution of the (3,4)He(e,e(')K+)(3,4)(Lambda)H processes to the elementary cross section 1H(e,e K+)Lambda on the free proton, measured during the same experiment.

Journal Article↗

Correlated strength in the nuclear spectral function.

We have carried out an (e,e'p) experiment at high momentum transfer and in parallel kinematics to measure the strength of the nuclear spectral function S(k,E) at high nucleon momenta k and large removal energies E. This strength is related to the presence of short-range and tensor correlations, and was known hitherto only indirectly and with considerable uncertainty from the lack of strength in the independent-particle region. This experiment locates by direct measurement the correlated strength predicted by theory.

Journal Article↗

Bovine aortic endothelial cells are susceptible to Hantaan virus infection.

Hantavirus serotype Hantaan (HTN) is one of the causative agents of hemorrhagic fever with renal syndrome (HFRS, lethality up to 10%). The natural host of HTN is Apodemus agrarius. Recent studies have shown that domestic animals like cattle are sporadically seropositive for hantaviruses. In the present study, the susceptibility of bovine aortic endothelial cells (BAEC) expressing alpha(V)beta(3)-integrin to a HTN infection was investigated. Viral nucleocapsid protein and genomic RNA segments were detected in infected BAEC by indirect immunofluorescence assay, Western blot analysis, and reverse transcription-polymerase chain reaction (RT-PCR), respectively. The results of this study strongly support our previous observation on Puumala virus (PUU) that has been propagated efficiently in BAEC. These findings open a new window to contemplate the ecology of hantavirus infection and transmission route from animal to man.

Animals↗

Measurement of the electric form factor of the neutron at Q2=0.5 and 1.0 GeV2/c2.

The electric form factor of the neutron was determined from measurements of the d-->(e-->,e'n)p reaction for quasielastic kinematics. Polarized electrons were scattered off a polarized deuterated ammonia (15ND3) target in which the deuteron polarization was perpendicular to the momentum transfer. The scattered electrons were detected in a magnetic spectrometer in coincidence with neutrons in a large solid angle detector. We find G(n)(E)=0.0526+/-0.0033(stat)+/-0.0026(sys) and 0.0454+/-0.0054+/-0.0037 at Q(2)=0.5 and 1.0 (GeV/c)(2), respectively.

Journal Article↗

Bovine aortic endothelial cells are susceptible to hantavirus infection; a new aspect in hantavirus ecology.

Hantaviruses are enveloped RNA viruses that belong to the family Bunyaviridae. They are the causative agents of hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). Hantaviruses show a worldwide distribution with specific rodent species as natural hosts. It is known that rodents can transmit the virus via feces, urine, saliva, or bites to humans. Additionally, antibodies against different hantaviruses were also found in domestic animals, For example, Danes et al. documented hantavirus-specific IgG titers in 2% of examined cattle [Ceskoslov. Epidemiol. Mikrobiol. Imunol. 41 (1992) 15]. In order to clarify the possibility of a nonrodent and nonhuman hantavirus infection, the susceptibility of bovine aortic endothelial cells (BAEC) to Hantavirus serotype Puumala infection was investigated. The hantaviral nucleocapsid protein was detected in 95% of infected BAEC at the fourth cell culture passage 12 weeks after initial infection by immunofluorescence assay (IFA). The presence of Puumala virus (PUU) nucleocapsid protein and the viral glycoproteins G1 and G2 in infected cells were additionally confirmed by Western blot analysis. The viral RNA genome was identified in infected BAEC cultures and in cell-free culture medium at the fourth passage by reverse transcription polymerase chain reaction (RT-PCR), verified by cDNA nucleotide sequence analysis, showing a 98-100% homology to the input virus. The infected BAEC cultures were shown to express alpha(V)beta(3)-integrin surface receptors that are known to mediate virus entry in human cells and revealed no major cytopathic effects (CPEs) as assayed by immunofluorescence staining of the cytoskeletal components actin and microtubules. In the present study, we documented for the first time that a nonrodent and nonhuman aortic endothelial cell culture of bovine origin (BAEC) can be efficiently infected with a hantavirus. This finding is of particular importance because it adds new aspects to questions dealing with host species barrier, viral reservoir, virus transmission, and ecology of hantaviruses.

Animals↗

Blood pressure profile and treatment quality in liver allograft recipients-benefit of tacrolimus versus cyclosporine.

Organ transplant recipients display a high cardiovascular mortality rate. The type of immunosuppression has a major impact on cardiovascular risk factors (e.g., hypertension [HTN]). We assessed 24-hour blood pressure (BP) and metabolic profiles in a cohort of 106 long-term liver allograft recipients treated with either tacrolimus (Tac) or cyclosporine (CyA). The median age of patients was 50.8 years (range, 11 to 77) and the median time of follow-up was 65.4 months (ranges 12 to 168). Immunosuppression included low-dose steroids and either Tac (n = 46) or CyA (n = 60). Twenty-four-hour BP measurements revealed a significant difference in systolic BP (127.1 mmHg [94 to 163] Tac versus 132.7 mmHg [103 to 177] CyA; P <.03), and in mean arterial and diastolic blood pressures. In addition, the relative number of normotensive patients was significantly higher among Tac-treated patients (69.6% versus 34.8%). It is of note that the true incidence of HTN was higher after the number of patients with a pathological 24-h BP measurement was added to the initial number of patients already known to have HTN. No less than 76.4% of all long-term liver transplanted patients showed HTN. The results were unrelated to cumulative steroid dosage, frequency of antirejection therapy or underlying primary liver disease. In summary, immunosuppression-induced HTN is more common in CyA-treated than Tac-based regimens. Moreover, we found a substantial lack of detection of HTN in long-term liver transplant patients who received an insufficient quality of antihypertensive treatment. These findings have implications for the early diagnosis and treatment of HTN in liver transplant recipients.

Blood Pressure↗

[Acute renal failure and hypertension crisis after a technoparty].

HISTORY: A 22 year old patient had noted progressive flank pain without recognizable urinary abnormalities for five days. INVESTIGATIONS: A urologist had noted increased serum creatine (2.1 mg/dl), hypertension (180/100 mmHg) and microhematuria. A post-renal cause was excluded by excretory urography. An interview revealed that the patient had consumed cocaine on weekends since age 19; the acute episode was preceded by a rave party with consumption of a total of 3 g of street quality cocaine. DIAGNOSIS AND TREATMENT: Because of microhematuria with a suggestive nephritic urinary sediment, the patient underwent renal biopsy. It showed acute tubular necrosis and interstitial edema, but no signs of glomerulonephritis and negative immunohistology. The patient received antihypertensive treatment. This led to rapid reversal of elevated serum creatinine and microhematuria was noted, but hypertension persisted. Currently the patient receives ACE inhibitors. CONCLUSION: Similar to what is seen in the US, cocaine use has to be considered in the differential diagnosis of acute renal failure with hypertension.

Acute Kidney Injury↗