Adverse effect of cis-diamminedichloroplatinum II (CDDP) on porphyrin metabolism in man

The possible effect of cisplatin on porphyrin metabolism was studied in 25 patients with various malignancies treated with high-dose cis-diamminedichloroplatinum. Haematocrit, red blood cells, haemoglobin, white blood cells, platelets and reticulocytes together with coproporphyrin and protoporphyrin in red blood cells were determined before each course of chemotherapy in all patients. In addition, coproporphyrin, uroporphyrin, δ-aminolevulinic acid, and porphobilinogen were determined in the urine just before and 24 h after each course of treatment. Cisplatin administration was followed by a significant suppression of coproporphyrin and protoporphyrin in red blood cells and coproporphyrin, uroporphyrin, δ-aminolevulinic acid and porphobilinogen in urine. The changes observed paralleled similar changes in haematocrit, red blood cells and haemoglobin, strongly suggesting that cisplatin-induced anaemia may be due to a blocking effect of the drug affecting one or more enzymatic steps in the biosynthesis of porphyrins and haem. A moderate fall in the white blood cell count and a mild fall in platelets together with a steady increase of reticulocytes were also observed during treatment. © 1986 Springer-Verlag

Dissociation of ACTH, beta-endorphin and cortisol in graded sepsis

The function of the hypothalamic-pituitary-adrenal axis as related to the degree of severity of a septic process was assessed by measuring plasma levels of beta-endorphin, ACTH and cortisol. Sixty-one cases of postoperative patients treated at the intensive care unit were classified into four groups according to the severity of infection: Group 1 (control) included patients who did not show any sign of infection, group 2 patients with sepsis, group 3 patients with septic syndrome and group 4 patients with septic shock. Compared to G1 patients’ ACTH values (4.16+/-2.6 pg/ml), a statistically significant increase in ACTH values in various stages of septicemia (p < 0.005) with a noticeable difference also between G3 (7.11 +/- 3.7 pg/ml) and G4 (11.5 +/- 6.6 pg/ml) (p<0.05) was found. Differences were also observed in beta-endorphin (with a level of significance between the several groups of p=0.0001). Also, beta-endorphin values in G4 (40.6 +/- 30.3 pg/ml) differed significantly from each of G1 (17.5 +/- 6.6 pg/ml), G2 (21.1 +/- 11.3 pg/ml) and G3 (23.5 +/- 12 pg/ mi) (p<0.05). A progressive hypercortisolemia was obvious, with values of G4 (37.2 +/- 15.6 mu g/dl) differing significantly from those of G1 (18 +/- 4.6 mu g/dl) and G2 (24 +/- 8.4 mu g/dl) (p<0.05) and of G3 (28.5 +/- 12.3 mu g/dl) from that of G1 (p < 0.05). Interestingly, a dissociation of ACTH, beta-endorphin and cortisol was observed, in that the increased values of beta-endorphin and cortisol, detected in the G3 were not associated with a parallel increase in ACTH. These findings might be interpreted in the sense of an impairment of the stress stimulation of the hypothalamic pituitary adrenal axis. Provided that such a situation can be lethal, our results further confirm the idea that a low-dose, steroid replacement might be beneficial to critical illness

Rapid extraction of fungal DNA from clinical samples for PCR amplification

A hexadecyltrimethylammonium bromide (CTAB) method for isolating fungal DNA from clinical samples, suitable for PCR amplification is described. Yeast and filamentous fungi DNA from clinical samples was amplified with primers complementary to the genes coding for rRNA, amplifying a 105 bp fragment and internal transcribed spacer primers amplifying fragments between 242 and 622 bp. The level of sensitivity was 10 ± 5 yeast and 28 Aspergillus fumigatus CFU ml-1 of biological fluid

GLOBIN CHAIN SYNTHESIS IN MYELODYSPLASTIC SYNDROMES

Globin chain synthesis was studied in the reticulocytes of 30 patients with various myelodysplastic syndromes (MDS) to determine the alpha:beta globin chain synthetic ratio and its probable prognostic value. The mean (SD) value of the total alpha:beta ratio was 0.82 (0.45) ranging from 0.05 to 1.73. The same ratio in 10 normal controls was 1.01 (0.04). This difference was significant. Furthermore, the alpha:beta ratios were lower than normal in 14 patients (alpha-thalassaemia-like) (group I), almost within normal limits in 11 (group II), and higher than normal in five (beta-thalassaemia-like) (group III). In each group almost all the FAB subtypes were represented. The addition of exogenous haem in several of the test samples resulted in a slight to pronounced increase in the alpha:beta ratios, particularly in group I. In 92% of the high risk cases (refractory anaemia with excess blasts (RAEB), chronic myelomonocytic leukaemia (CMML)) or 87.5% of patients who finally developed acute non-lyphoid leukaemia (ANLL) low or normal alpha:beta ratios were found. No significant correlation was noticed between alpha:beta ratios and various haematological variables or survival. It is concluded that in MDS the alpha:beta ratio varied enormously across the entire population of patients, as well as within each FAB subtype, thereby restricting its prognostic value. Although haem deficiency may be implicated in some cases of MDS, why this should be remains unclear