Dietrich Michalk

A stepwise approach to the treatment of early onset nephrotic syndrome.

Abstract We have retrospectively reviewed our single-center experience of the treatment of early onset nephrotic syndrome (NS). From 1991 to 1998, ten children with NS were treated. Kidney biopsy showed focal sclerosis (n=1), diffuse mesangial sclerosis (n=7), and congenital NS of the Finnish type (n=2). Associated conditions included incomplete Drash syndrome (n=1), Galloway-Mowat syndrome (n=1), and severe mental and motor retardation of unknown origin (n=3). From 1991 to 1997, five children with NS were treated. Bilateral nephrectomy (NX) was performed in three, one patient with severe retardation died at 4 years and NX was not performed in one patient who showed satisfactory growth and development. Three of these children were dialyzed and two were successfully transplanted. One patient was transplanted without previous dialysis. From 1997 to 1998, five children were treated with a regimen that included captopril and indomethacin (CAPTO/INDO). CAPTO/ INDO was successful in increasing serum protein in all patients and producing growth and development in four patients. In two patients CAPTO/INDO was successful only after unilateral NX. Our experience indicates that CAPTO/INDO may be a valuable treatment in patients with early onset NS. An individualized stepwise approach including unilateral NX should be considered to achieve optimal results.

Mitochondrial Diseases ‐ An Expanding Spectrum of Disorders and Affected Genes

Mitochondrial diseases are a heterogeneous group of disorders caused by the impairment of the mitochondrial oxidative phosphorylation system which have been associated with various mutations of the mitochondrial DNA (mtDNA) and nuclear gene mutations. The clinical phenotypes are very diverse and the spectrum is still expanding. This review gives an overview of the principal clinical phenotypes and the molecular genetic basis of mitochondrial disorders identified so far.

The Mechanisms of Taurine Mediated Protection against Cell Damage Induced by Hypoxia and Reoxygenation

Taurine administered during hypoxia markedly reduced the cell damage due to O2 deficiency and reoxygenation. Different mechanisms are responsible for the improved survival of the renal cell cultures. Taurine markedly reduces the osmoregulatory deterioration during hypoxia and reoxygenation. Calcium homeostasis was markedly improved. Ca2+ efflux during hypoxia as well as Ca2+ overload during reoxygenation was significantly reduced by the amino acid. The effect of taurine was partly comparable to the effect induced by Ca2+ channel blockers. One of the effects mainly responsible for cellular protection seems to be the taurine-induced acceleration of cellular growth processes in spite of hypoxia and reoxygenation. The spectrum of cytoprotective effects of taurine predisposes this substance to be a physiological protective agent responsible for cellular homeostasis or enantiostasis.

Taurine reduces renal ischemia/reperfusion injury in the rat.

In renal transplantation, the deleterious effect of ischemia/reperfusion injury has a major impact on graft survival by triggering or influencing acute rejection as well as late chronic changes12. Thus protective maneuvers at the time of transplantation should ameliorate the fate of the organ.

Taurine Reduces Experimental Liver Injury after Cold Ischemic Preservation and a Period of Rewarming Prior to Reperfusion

Livers of male Wistar rats (250-300 g) were isolated and flushed with 10 ml of Ringers solution and 10 ml of UW preservation solution. Then the organs were stored for 24 h at 4 degrees C in UW solution. Livers of Group 1 were rinsed with 10 ml of Ringers solution and reperfused after hypothermic storage with oxygenated Krebs-Henseleit solution (95% O2; 5% CO2) in a nonrecirculating system at constant pressure (10 mmHg) and 37 degrees C. Livers of Group 2 were incubated for 30 min at 37 degrees C prior to reperfusion, in order to simulate rewarming of the organ upon surgical implantation. Livers of Group 3 were treated like Group 2, but taurine was admixed to the UW solution (1 mM). Livers of Group 1 showed little signs of a preservation/reperfusion injury, with low enzyme activities of the parenchymal ALT and endothelial purine nucleoside phosphorylase (PNP) in the postischemic rinse solution (ALT: 19.9 +/- 12.4; PNP: 3.3 +/- 0.4 U/liter), adequate portal flow values about 3 ml/g/min and high O2 uptake at the end of the experiment (VO2: 3.2 +/- 0.4 ml/100g/min). Livers of Group 2 exhibited nearly tenfold higher enzyme activities in the rinse solution (ALT: 247.0 +/- 94.7*; PNP: 29.5 +/- 17.0* U/l) and disturbed tissue perfusion with significantly reduced flow values of about 2 ml/g/min during the first 10 min of reperfusion. As a result, the recovery of O2 uptake was only 2.2 +/- 0.3 ml/100 g/min*. Addition of taurine (Group 3) resulted in a significant reduction of the enzyme loss (ALT: 96.2 +/- 50.0#; PNP:12.4 +/- 7.0# U/liter) and improved portal flow values and O2 uptake at the end of reperfusion (2.7 +/- 0.3 ml/100 g/min#). The results give evidence for the importance of the rewarming period after hypothermic storage, which is inevitable during implantation of the organ in vivo. Taurine seems to exert a protective effect, affecting both the vascular endothelium and parenchymal tissue (*p < 0.05 vs Group 1; # p < 0.05 vs Group 2).

Protection against cell damage due to hypoxia and reoxygenation: The role of taurine and the involved mechanisms

SummaryThe effect of taurine on cell viability and metabolism of human colon and porcine renal cells was investigated during and after hypoxia. Taurine administered during hypoxia markedly reduced cellular deterioration due to hypoxia and reoxygenation and led to a significantly greater recovery of cellular function following the hypoxic insult. The responsible mechanisms for the beneficial effects were an improvement in osmotic status and calcium homeostasis and an induction in cellular growth despite oxygen deficiency and reoxygenation. Free oxygen radical generation and lipid membrane peroxidation were not reduced by taurine. Taurine acted as a potent endogenous agent with multifactorial effects against cellular damage due to hypoxia and reoxygenation.

Acute glaucoma and intracranial hypertension in a child on long-term peritoneal dialysis treated with growth hormone

A 7-year-old boy with end-stage renal disease on long-term peritoneal dialysis is described. The child developed intracranial hypertension and acute glaucoma during therapy with recombinant human growth hormone (rhGH), 18 months after the onset of treatment. Symptoms developed within 1.5 days and required neurosurgical treatment to reduce the intracranial hypertension because of imminent impaction of the cerebellum and brain stem. After ventricular cerebrospinal fluid drainage and cessation of growth hormone, all symptoms of intracranial hypertension and increased intraocular pressure disappeared. To our knowledge this is the first report of intracranial hypertension or hydrocephalusand acute glaucoma during rhGH therapy. Continuous and long-term control of the ophthalmological and neurological status of patients treated with rhGh is indicated.

Peer teaching in paediatrics - medical students as learners and teachers on a paediatric course.

Background: Peer assisted learning is known as an effective educational strategy in medical teaching. We established a peer assisted teaching program by student tutors with a focus on clinical competencies for students during their practical training on paediatric wards. It was the purpose of this study to investigate the effects of a clinical skills training by tutors, residents and consultants on students evaluations of the teaching quality and the effects of a peer teaching program on self assessed clinical competencies by the students. Methods: Medical student peers in their 6th year were trained by an intensive instruction program for teaching clinical skills by paediatric consultants, doctors and psychologists. 109 students in their 5th year (study group) participated in a peer assisted teaching program for training clinical skills in paediatrics. The skills training by student peer teachers were supervised by paediatric doctors. 45 students (control group) participated in a conventional paediatric skills training by paediatric doctors and consultants. Students from both groups, which were consecutively investigated, completed a questionnaire with an evaluation of the satisfaction with their practical training and a self assessment of their practical competencies. Results: The paediatric skills training with student peer teachers received significantly better ratings than the conventional skills training by paediatric doctors concerning both the quality of the practical training and the support by the teaching medical staff. Self assessed learning success in practical skills was higher rated in the peer teaching program than in the conventional training. Conclusions: The peer assisted teaching program of paediatric skills training was rated higher by the students regarding their satisfaction with the teaching quality and their self assessment of the acquired skills. Clinical skills training by student peer teachers have to be supervised by paediatric doctors. Paediatric doctors seem to be more motivated for their own teaching tasks if they are assisted by student peer teachers. More research is needed to investigate the influence of peer teaching on the motivation of paediatric doctors to teach medical students und the academic performance of the student peers.

Influence of Taurine Supplementation on Ischemic Preservation of the Isolated Rat Kidney

Taurine (2-aminoethanesulfonic acid) is an endogenous amino acid with unique functions as a modulator of transmembraneous calcium transport, an osmoregulator and putatively a free radical scavenger4,7,12.

Protecting effect of Taurine against Hypoxic Cell Damage in Renal Tubular Cells Cultured in Different Transplant Preservation Solutions

We conclude that, within this experimental model and under these experimental conditions, taurine supplementation of standard kidney preservation solutions improves survival of kidney cells during hypoxic preservation. The protective effect depends on the taurine concentration, the hypoxic preservation time and the used preservation solution. Physiological taurine concentrations are effective during short hypoxic periods, whereas pharmacological taurine concentrations seem to be needed for longer periods of hypoxia. Within this experimental model University of Wisconsin solution seems to be more effective than Euro collins solution.