Oral iron chelating therapy. A single center interim report on deferiprone (L1) in thalassemia.

BACKGROUND AND OBJECTIVE: Deferiprone (L1) is a largely studied oral chelator in clinical setting, however, no definite conclusions concerning efficacy and toxicity still could be drawn. In an ongoing prospective trial with L1, we evaluated the efficacy and tolerance-toxicity in patients with thalassemia major previously treated by desferrioxamine (DFO); the specific aim of the study is to demonstrate that L1 could be an alternative to DFO in some patients with an acceptable toxicity. DESIGN AND METHODS: Sixty-nine patients over 13 years of age with poor compliance to DFO were considered for the study. The design included a liver biopsy before starting L1 in all patients in order to define liver siderosis either by histologic grading or by hepatic iron concentration (HIC); only patients with a minimum HIC of 4 mg/g dry weight entered the study. A repetition of the liver biopsy after one year of L1 was planned; further evaluations included serum ferritin, plasma iron, transferrin TIBC and iron urine excretion. L1 was given at 70 mg/kg/day in three divided doses. Toxicity was monitored either clinically or by controlling liver, kidney and marrow function by specific tests. Concerning clinical characteristics 52 patients showed hypogonadism (78%), 39 growth retardation (58%), 6 diabetes (9%), 4 cardiomyopathy (6%), 9 hypothyroidism (12%); 45 patients had chronic liver damage (65%). RESULTS: We focus this report on data collected in a group of 29 patients with a minimum follow-up of one year (14-33 months). The mean ferritin value was 3748 ng/mL (range: 200-10,000) and 2550 ng/mL (range: 80-14,500), before and while on L1 therapy, respectively (p = 0.001); the mean sideruria changed from 17.25 mg/dL (range: 5.4-50) to 20.98 mg/dL (range: 10-40), on DFO and L1, respectively (p = 0.078); the ratio between plasma iron (sideremia) and transferrin TIBC changed from 0.96 with DFO to 0.86 with L1 (0.014). A correlation with grade of liver siderosis and serum ferritin (p = 0.069) and iron urine excretion (p = 0.008) was recorded. The judgement of efficacy showed that L1 was effective (EF) in 9 patients, no assessable (UN) in 11 patients, not effective (NE) in 2 patients and with no advantages with respect to DFO in 7 patients. Liver biopsy was repeated in 20 patients showing a reduction of grade of liver siderosis and iron content in 7 patients. Clinical toxic effects of L1 were gastric intolerance (one patient), joint pain (three patients) and mild and temporary neutropenia (one patient). INTERPRETATION AND CONCLUSIONS: This preliminary experience shows that L1 is effective in several patients with thalassemia with poor compliance to DFO and to improve iron burden and iron excretion with generally minor side effects. L1 could be an alternative to DFO in some patients, however the recognition of neutropenia warrants a careful evaluation of patients and efforts finalized to early recognition of those to be addressed with this new and still experimental therapy.

Acute renal failure due to tubular necrosis caused by wildfowl-mediated hemlock poisoning.

We report the clinical and histological findings in patients with acute renal failure caused by the ingestion of wildfowl who had eaten hemlock buds. Neurotoxic effects were accompanied by rhabdomyolysis, myoglobinuria, and acute tubular necrosis. Histological studies showed diffuse degeneration of the tubular epithelium. Immunohistological studies demonstrated the presence of myoglobin and actin in renal tubular cells.

First exchange neutrophilia is not always an index of peritonitis during CAPD.

To date, the medical literature suggests that CAPD patients with peritonitis have an increase in the dialysate white cell count (greater than 100 cells mL) with neutrophilia (greater than 50%). In order to explore the differential composition of the peritoneal fluid cells (P.F.C.), we have followed 21 patients (PTS) twice a month over a 30-month period. Nine hundred and fifty samples obtained either from the 24 hours (hrs) drained CAPD fluid, or from the "First Morning Exchange" (F.M.E.) during the same day, when possible, were estimated with the "Millipore Filter" (5-8 Micron (lw) pore size), stained by the Papanicolau method. The results can be so summarized: (1) 13 PTS (62%) showed constantly a low polynuclear count (3-32%); (2) 8 non-infected PTS (38%) showed constantly a higher neutrophilia (40-80%); and (3) from time to time the PTS of the two groups showed a higher neutrophilia and an increased cellularity during clinical infection. In all the samples, the differential P.F.C. count was not affected by the dialysate composition and no difference was observed between the 24 hrs samples and the F.M.E. samples made on the same day. Differential peritoneal cell count may be useful when there are important changes in the stable individual composition.