[The clinical spectrum of urea cycle defects in adult patients]. / Das klinische Spektrum von Harnstoffzyklusdefekten im Erwachsenenalter.

Urea cycle defects belong to the most common metabolic disorders with a cumulative incidence of 1:8000. A common trait of urea cycle defects is a disturbed detoxification of ammonia leading to hyperammonemia in the event of a high nitrogen load. Most patients develop symptoms in the neonatal period or in infancy, e. g. vomiting, seizures and disturbed consciousness. Depending on the affected enzyme and its residual activity, patients differ in the age at first presentation, the character and severity of symptoms and in the susceptibility to metabolic derangement. The presence of hyperammonemia and an altered plasma amino acid profile give the essential diagnostic clues. Since modern therapeutic measures have prolonged the life expectancy of these patients and provided the possibility of a first presentation in adulthood, patients with urea cycle defects have become an increasing challenge in internal medicine. The reported case series illustrates the heterogeneous clinical course of these disorders from childhood to adulthood.

Centrosome aberrations as a possible mechanism for chromosomal instability in non-Hodgkin's lymphoma.

Recently, centrosome aberrations have been described as a possible cause of aneuploidy in many solid tumors. To investigate whether centrosome aberrations occur in non-Hodgkin's lymphoma (NHL) and correlate with histologic subtype, karyotype, and other biological disease features, we examined 24 follicular lymphomas (FL), 18 diffuse large-B-cell lymphomas (DLCL), 33 mantle cell lymphomas (MCL), and 17 extranodal marginal zone B-cell lymphomas (MZBCL), using antibodies to centrosomal proteins. All 92 NHL displayed numerical and structural centrosome aberrations as compared to nonmalignant lymphoid tissue. Centrosome abnormalities were detectable in 32.3% of the cells in NHL, but in only 5.5% of lymphoid cells from 30 control individuals (P<0.0001). Indolent FL and MZBCL contained only 25.8 and 28.8% cells with abnormal centrosomes. In contrast, aggressive DLCL and MCL harbored centrosome aberrations in 41.8 and 35.0% of the cells, respectively (P<0.0001). Centrosomal aberrations correlated to lymphoma grade, mitotic, and proliferation indices, but not to the p53 labeling index. Importantly, diploid MCL contained 31.2% cells with abnormal centrosomes, while tetraploid samples harbored centrosome aberrations in 55.6% of the cells (P<0.0001). These results indicate that centrosome defects are common in NHL and suggest that they may contribute to the acquisition of chromosomal instability typically seen in NHL.

Mass spectrometry of a volatile Mg chelate in the measurement of stable 26Mg when used as a tracer.

A method for the detection of 26Mg enrichment of natural Mg was developed based on mass spectrometry (MS) of a Mg chelate made by complexing Mg to 2,2',6,6'-tetramethylheptanedione (THD). The chelate [Mg(THD)2] was extracted at pH greater than 9 from dilute aqueous solutions into ethyl ether, recovered by sublimation at room temperature, and introduced by solid probe into a Finnigan 3300 mass spectrometer. The chelate was ionized by electron impact. Samples were heated to a maximum temperature of 200 degrees C at a rate of 700 degrees C/h. Each analysis required 1--5 micrograms Mg(THD)2. Enrichment levels as low as 5% above natural abundance could be detected satisfactorily. Precision was best at 26Mg enrichment levels of 8--40% above natural abundance, the levels most likely to be encountered in analysis of plasma, urine and fecal samples from experimental subjects who had received 26Mg as a tracer. The method was compared to neutron activation (NA) analysis and judged superior.