delta-Aminolaevulinic acid dehydratase as an index of lead toxicity. Time for a reappraisal?

delta-Aminolaevulinic acid dehydratase activity is traditionally accepted as the most sensitive measurable biological index of lead toxicity. We have measured delta-aminolaevulinic acid dehydratase activity and blood lead concentration in 47 healthy controls (A), 42 iron deficient patients (B) and 38 occupationally exposed to lead subjects (C). Blood lead levels [mean (SD)] did not differ between groups A and B [0.51 (0.21) and 0.43 (0.19) mumol L-1, respectively] while those of group C [2.28 (0.56) mumol L-1 were significantly higher (P < 0.001) as compared to the controls. delta-Aminolaevulinic acid dehydratase activity [mean (SD)] was significantly increased [3599 (1909) mumol L-1 h-1] in group B and decreased in group C [1052 (532) mumol L-1 h-1] as compared to the controls [2034 (446) mumol L-1 h-1] (P < 0.001). There was a significantly negative correlation of logarithm of delta-aminolaevulinic acid dehydratase with lead in both groups B (P < 0.05) and C (P < 0.001) but not in group A (P = 0.1). delta-Aminolaevulinic acid dehydratase activity had a high specificity (100%) but a low sensitivity (37%) as an index of toxic lead exposure. According to our data the value of delta-aminolaevulinic acid dehydratase measurement in the diagnosis of lead intoxication is doubtful in cases with low blood lead levels, while in the presence of iron deficiency its reliability is further reduced, since low blood lead levels may be falsely predicted. delta-Aminolaevulinic acid dehydratase activity should be restricted only to monitoring cases with moderate or severe lead poisoning.

Thrombotic thrombocytopenic purpura: a multimodality model of treatment including plasma exchange, i.v. immunoglobulin, prednisone, antiplatelet agents, vincristine and splenectomy.

Thirteen patients with thrombotic thrombocytopenic purpura were treated at our facility between 1985 and 1991. All patients were treated with plasma therapy (both plasma exchange and plasma infusions), prednisone, intravenous immunoglobulin, and antiplatelet agents. Twelve patients achieved remission (92.3%). One patient died from cerebral hemorrhage. Vincristine was administered to 5 patients who did not respond after the first two plasmaphereses. Splenectomy was performed in a patient who relapsed four times within a 2-year period. From the 12 patients achieving remission, 11 have been still in remission for a period of 3 to 69 months.

Treatment of myelodysplastic syndromes with human granulocytic-macrophage colony stimulating factor (GM-CSF) or GM-CSF combined with low-dose cytosine arabinoside.

In a phase II study, 21 patients with MDS (RAEB, RAEBt, CMML and RA and RAS with severe cytopenia) were randomized to be treated with 3 courses of GM-CSF (3 micrograms/kg/day s.c.) alone (11 patients) or in combination with AraC (20 mg/m2/d s.c.) (10 patients) for 14-d periods, interrupted by 14-d rest periods. Eight patients discontinued the treatment. In the GM-CSF group a marked increase in WBC and neutrophil counts during each course of treatment administration were seen in most patients. Platelet counts decreased in 14 of 24 courses of treatment in the GM-CSF plus AraC group but in none of the GM-CSF group. Although the changes in the circulating blood cells were transient and the counts tended to return to the pretreatment levels during the rest periods, some more durable effects were seen. In 3/6 patients of the GM-CSF group who completed the designed treatment, both WBC and neutrophils remained elevated above the pretreatment levels throughout the 3-month period of treatment, while in one of them thrombocytopenia improved considerably. In the GM-CSF plus AraC group, 4 out of the 7 patients who completed the treatment showed an improvement of neutropenia as well as anaemia. In these 4 patients the BM percentage of blasts was also decreased. In conclusion, the results of this study indicate that GM-CSF given intermittently improves leukopenia in some patients with MDS. In addition, the administration of GM-CSF seems to prevent granulocytopenia of concurrent AraC treatment and may be of benefit in the treatment of these diseases.