Renal magnesium wasting in two families with autosomal dominant inheritance

Hypomagnesemia due to isolated renal magnesium loss was demonstrated in two unrelated families with autosomal dominant mode of inheritance. Magnesium infusions performed in two patients showed not only a reduced renal magnesium threshold but also a lowered renal tubular maximum for magnesium. All members of both families who presented with hypomagnesemia had also a lowered excretion of calcium in the urine, presumably as a consequence of increased reabsorption in Henle's loop.     

Moderne Pharmakotherapie bei supraventrikulären und ventrikulären Herzrhythmusstörungen

Currently the pharmacological approach still represents the mainstay in the acute phase of arrhythmia management as well as in the chronic treatment phase of specific entities such as atrial fibrillation. However, non-pharmacological options have recently emerged as frequently used first-line tools for the treatment of various supraventricular and ventricular heart rhythm disturbances. Nevertheless, antiarrhythmic drug treatment is frequently used as a bridging or adjunctive therapy in conjunction with catheter ablation or implantable cardioverter defibrillators. Antiarrhythmic agents constitute a very heterogeneous group prone to various drug interactions and side-effects. Therefore, this article aims to summarise the most important facts and recent findings with regard to appropriate contemporary pharmacological therapy of atrial and ventricular arrhythmias in clinical practice.     

Distinction between renal and nonrenal hematuria using immunoperoxidase staining of erythrocytes in urine for Tamm-Horsfall protein]

A recently described immunocytochemical staining method to distinguish renal from non-renal haematuria was adapted for use in the standard clinical chemical laboratory. The method is based on the observation that only in case of renal haematuria are erythrocytes in urine coated with so-called Tamm-Horsfall protein, originating from the renal tubuli. Erythrocytes in urine were stained using an indirect immunoperoxidase method, resulting in cells with dark-brown stained surfaces. The staining methods were validated with material from clinically diagnosed cases of haematuria of renal or non-renal origin and compared with scores of the number of dysmorphic erythrocytes, another method to distinguish renal from non-renal haematuria. In specimens of presumed strictly renal haematuria 86% (SD 8.7; n = 26) of the erythrocytes stained immunocytochemically. However, in specimens of haematuria originating from bleeding in the renal pelvis few cells stained (6%; SD 5.8; n = 4). In specimens of purely non-renal haematuria only 13% (SD 13.5; n = 21) stained. Immunocytochemical staining of erythrocytes permitted a much better distinction between renal and non-renal haematuria, with better sensitivity and specificity, than the inspection of erythrocyte morphology. We conclude that immunochemical staining of erythrocytes in urine is a valuable method for distinguishing renal and non-renal haematuria.     

Loss of constitutional heterozygosity in human astrocytomas

Summary Inactivation of tumour suppressor genes or anti-oncogenes as well as activation of dominant acting oncogenes seem to be important mechanisms in the pathogenesis of gliomas. We compared constitutional and tumoural genotypes at different restriction fragment length polymorphism loci (RFLP) on chromosomes 10 and 17 in 15 unrelated individualsLoss of heterozygosity (LOH) pointing to chromosomal loss or deletions was detected for at least one chromosme 17 marker in 11 gliomas (astrocytomas grades I–III and glioblastoma multiforme), whereas LOH for chromosome 10 loci was only detected in 3 out of 9 cases of glioblastoma multiforme and was not detected in low grade gliomas. Since LOH for chromosome 10 loci seems to be restricted only to glioblastoma multiforme, it is possible that recessive mutations on chromosome 10 are engaged in tumour progression from astrocytomas to glioblastoma multiforme. As LOH of chromosome 17 markers occurs in astrocytomas as in glioblastoma multiforme, chromosome 17 loci probably are involved in early tumour development.     

A scoring system for basic cardiac life support skills in training situations.

A valid and reproducible system for determining basic cardiac life support (BCLS) skills can help to evaluate the effect of instruction courses and to estimate the results of educational activities. The aim of this study was to develop and test such a system in accordance with the Standards and Guidelines of the American Heart Association (AHA). Five criteria were defined in advance towards such a system (1) Inadequate techniques must be reflected by a fail score. (2) Skilled persons should achieve a pass score. (3) The effect of training must be reflected by an improvement of the score. (4) Inter- and intra-observer variability must be negligible. (5) The system should be simple to apply. The system was developed, and in order to test the system, the BCLS skills of 40 ambulance nurses were tested once and those of 148 lay people twice. All cardiopulmonary resuscitation (CPR) attempts were performed on a mannequin. The relevant parameters of the attempt were continuously recorded and printed. Penalty points were assigned in a predefined way for aberrations of the techniques advised in the Standards and Guidelines. The system satisfied the five criteria mentioned above. It therefore offers a reliable and reproducible evaluation of BCLS skills.     

Peritoneal protein loss in children with nephrotic syndrome during peritoneal dialysis

Background: The passage of proteins across the glomerular filtration barrier is mainly determined by the size of the protein. In nephrotic syndrome (NS) the glomerular permselectivity is affected, causing proteinuria. Some authors suggest the existence of a generalized basement membrane defect. The permeability characteristics of the peritoneal basement membrane in children with NS are not known. Methods: The transperitoneal transport of proteins with a different molecular weight ({beta}2-microglobulin MW 11 800 D, albumin MW 69 000 D, IgG MW 160 000 D, and &agr;2-macroglobulin MW 820 000 D) was studied in a study group (group A) consisting of six stable nephrotic children (three with glomerulosclerosis and three with congenital nephrotic syndrome, one of them with mesangial sclerosis) and compared to a control group (group B) consisting of eight stable children on peritoneal dialysis. After a dwell of 6 h with Dianeal 1.36% dialysate and serum samples were collected. For each patient the dialysate to plasma (D/P) ratio of the four proteins were calculated. The D/P ratios of the nephrotic patients in group A were compared to the D/P ratios of the patients in the control group B. Data were expressed as mean ±SD. Results: The values for the D/P ratios (in percentage) of {beta}2-microglobulin, albumin, IgG and &agr;2-macroglobulin in group A were 19.6±9.9, 2.7±1.7, 1.6±0.9, and 0.5±0.4, compared to 24.9±10.2, 4.0±2.3, 2.2±1.2, and 0.7±0.3 in the control group B. The ratios were plotted against MW on a double logarithmic scale. In all patients a linear relationship between molecular weight and D/P ratio of the proteins was obtained. The D/P ratios of the study group did no differ significantly from the control group. Conclusion: We conclude that the size selectivity of the capillary permeability is not affected in the peritoneal membrane in children with NS due to glomerulosclerosis and congenital nephrotic syndrome.     

Comparative genotyping of Campylobacter jejuni by amplified fragment length polymorphism,multilocus sequence typing,and short repeat sequencing: strain diversity,host range,and recombination

Three molecular typing methods were used to study the relationships among 184 Campylobacter strains isolated from humans, cattle, and chickens. All strains were genotyped by amplified fragment length polymorphism (AFLP) analysis, multilocus sequence typing (MLST), and sequence analysis of a genomic region with short tandem repeats designated clustered regularly interspaced short palindromic repeats (CRISPRs). MLST and AFLP analysis yielded more than 100 different profiles and patterns, respectively. These multiple-locus typing methods resulted in similar genetic clustering, indicating that both are useful in disclosing genetic relationships between Campylobacter jejuni isolates. Group separation analysis of the AFLP analysis and MLST data revealed an unexpected association between cattle and human strains, suggesting a common source of infection. Analysis of the polymorphic CRISPR region carrying short repeats allowed about two-thirds of the typeable strains to be distinguished, similar to AFLP analysis and MLST. The three methods proved to be equally powerful in identifying strains from outbreaks of human campylobacteriosis. Analysis of the MLST data showed that intra- and interspecies recombination occurs frequently and that the role of recombination in sequence variation is 50 times greater than that of mutation. Examination of strains cultured from cecum swabs revealed that individual chickens harbored multiple Campylobacter strain types and that some genotypes were found in more than one chicken. We conclude that typing of Campylobacter strains is useful for identification of outbreaks but is probably not useful for source tracing and global epidemiology because of carriage of strains of multiple types and an extremely high diversity of strains in animals.     

Impaired responses to toll-like receptor 4 and toll-like receptor 3 ligands in human cord blood

Toll-like receptor (TLR)-4 signaling pathway plays an essential role in host defense against gram-negative bacteria while TLR-3-mediated signaling is critically involved in anti-viral immunity. To gain insight into the defects responsible for impaired Th1 responses in human newborns, we investigated the responses of human cord blood cells to lipopolysaccharide, LPS, and to polyinosinic-polycytidylic acid, Poly (I:C), ligands of TLR-4 and TLR-3, respectively. Measurement of cytokine levels revealed a profound defect in IL-12 (p70) synthesis and an increased release of IL-10 in cord blood exposed to LPS or Poly (I:C), as compared to adult blood. Moreover, Poly (I:C)-induced IFN-alpha production was found to be significantly impaired in cord blood. Phenotypic maturation of myeloid DC in response to LPS or Poly (I:C) was next compared in cord and adult blood. We observed that neonatal myeloid DC displayed decreased upregulation of CD40, CD80 whereas CD86 and HLA-DR upregulation did not differ significantly between adults and neonates. Taken together, these findings might be relevant to the increased vulnerability of human newborns to intracellular pathogens and to their inability to develop efficient Th1-type responses.