John W. Graef

Methotrexate-induced congenital malformations.

The case of an infant born after the unsuccessful abortifacient use of methotrexate is reported. The resulting multiple congenital anomalies included absence of the frontal bone, synostosis of the lambdoid and coronal sutures, multiple anomalous ribs, unusual facies, and absence of digits on the left foot with only one digit on the right foot. Mental and motor development was normal, but growth was markedly retarded. The clinical data are compared with 7 other reported cases. The high incidence of cranial anomalies is noted.

Lead intoxication in children with pervasive developmental disorders.

OBJECTIVE To investigate the observation that children with pervasive developmental disorders have later and more prolonged lead exposure and are more likely to be reexposed when compared to lead-poisoned children without pervasive developmental disorders. DESIGN Retrospective chart review. SETTING A large, urban lead treatment program. RESULTS Over a six year period 17 children with pervasive developmental disorders (including autism) were treated. Compared to a randomly selected group of 30 children without pervasive developmental disorders who were treated for plumbism over the sam interval, those with pervasive developmental delay were significantly older at diagnosis (46.5 vs 30.3 months, p = .03) and had a longer period of elevated blood lead levels (39.1 vs 14.1 months, p = .013) during management. Despite close monitoring, state-mandated environmental inspection and prompt lead hazard reduction or alternative housing, 75% of children with pervasive developmental disorders were reexposed to lead during medical management compared with 23% of children without pervasive developmental disorders (p = .001). CONCLUSIONS 1) lead intoxication among children with pervasive developmental disorders may appear de novo beyond the third year of life and is associated with a high rate of reexposure; 2) the provision of deleaded housing (by current techniques) may not be sufficient to protect these children from repeated lead exposure; 3) these data support recommendations by the Centers for Disease Control that children with developmental delays be closely monitored for the appearance of lead intoxication. This monitoring should continue beyond the third year of life.

A case report of lead paint poisoning during renovation of a Victorian farmhouse.

We describe a series of four cases of childhood lead poisoning and two cases of adult lead toxicity in a professional family exposed to lead dust and fume during renovation of a rural farmhouse. Initial blood lead levels in the children ranged from 2.70 to 4.20 microM/L (56 to 87 microns/dl) and all four required chelation therapy. Lead-based paint poisoning, a well recognized entity among young children in poor, urban neighborhoods, is not confined exclusively to such areas.

Efficacy and toxicity of d-penicillamine in low-level lead poisoning

In a retrospective cohort study we reviewed our experience using D-penicillamine in children with low-level lead poisoning (whole blood lead levels 25 to 40 micrograms/dL) to determine its efficacy and the incidence of side effects. Two groups were compared: treated subjects (n = 84) were treated with penicillamine at a mean daily dose of 27.5 mg/kg; control subjects (n = 37) received no chelation therapy. Over a prechelation observation period of 60 days, lead levels (PbB) did not change in either group. With a mean period of 76 days of D-penicillamine therapy, PbB fell in treated patients by 33% (P less than 0.001). In 64 patients (76%), PbB was reduced to a currently acceptable range (less than or equal to 25 micrograms/dL). There were eight treatment failures (10%). In control subjects, mean PbB did not change significantly over 119 days of observation. Fourteen control subjects eventually required conventional chelation with calcium disodium ethylene-diaminetetraacetic acid, and 17 were lost to follow-up. Use of D-penicillamine was associated with an adverse reaction in 28 cases (33%); transient leukopenia occurred in eight, rash in seven, transient platelet count depression in seven, enuresis in three, and abdominal pain in two. Treatment was terminated prematurely in eight cases (10%) because of an adverse reaction. We conclude that D-penicillamine is effective therapy for selected children with low-level plumbism, but adverse effects can complicate or prevent its use in some patients.

Efficacy of oral meso-2,3- dimercaptosuccinic acid therapy for low-level childhood plumbism☆☆☆★

OBJECTIVE To compare the response to oral meso-2,3-dimercaptosuccinic acid (DMSA) treatment in children with an initial blood lead (BPb) concentration less than versus more than 2.17 mumol/L (45 micrograms/dl). DESIGN Retrospective cohort study. SETTING Regional referral lead treatment program in an urban childrens hospital. PATIENTS Thirty consecutive children, median age 34 months (range, 5 to 161 months), with an initial BPb concentration 0.97 to 2.90 mumol/L (20 to 60 micrograms/dl) selected for DMSA use. Reasons for DMSA use included BPb concentration > 2.17 mumol/L (11 children), complications with penicillamine therapy (11), chronic renal failure (1), and compassionate use (7). All patients received required environmental hazard reductions before drug administration. RESULTS Group 1 (n = 23) had a mean BPb concentration of 1.50 mumol/L (31 micrograms/dl), and group 2 (n = 7) had a mean BPb concentration of 2.41 (51 micrograms/dl). Sixteen patients (70%) in group 1 and five patients (71%) in group 2 had had previous chelation therapy (p value not significant). No significant difference was found in the mean percentage of the reduction of BPb concentration during treatment of group 1 (60%) versus group 2 (58%). The mean BPb concentration in group 1 rebounded to 70% of pretreatment values by mean day 41; the BPb concentration in group 2 rebounded to 69% by day 37 (p value not significant). Prior chelation therapy did not result in a significant difference in either the percentage reduction of BPb concentration or the percentage of rebound BPb. CONCLUSION DMSA is equally effective in acutely lowering BPb concentration in children with BPb concentrations less than and greater than 2.17 mumol/L.

Acute high-dose lead exposure from beverage contaminated by traditional Mexican pottery

Screening and follow-up blood lead measurements in a 7-year-old child of a US Embassy official in Mexico City revealed an increase in blood lead concentration from 1.10 to 4.60 mumol/L in less than 4 weeks. The cause was traced to fruit punch contaminated with lead leached from traditional ceramic pottery urns. Consumption of the contaminated punch at a picnic was associated with a 20% increase in blood lead concentrations among embassy staff and dependants who were tested 6 weeks after the exposure. This episode highlights the continued health risk, even from brief exposure, posed by traditional pottery in Mexico.

Lead Intoxication From Lead-contaminated Water Used to Reconstitute Infant Formula

The lead found in drinking water can be a source of lead poisoning to young children, particularly those who consume large amounts of water. The authors describe a 13-month-old infant who was discovered to have plumbism during routine evaluation. The lead source was ultimately traced to the daily administration of powdered formula which was prepared with home tap water having a first-draw lead content of 130 parts per billion. This case suggests that whenever infants are fed powdered formula, consideration should be given to analysis of the home tap water for lead content.

The effect of phytohemagglutinin on the DNA-dependent RNA polymerase activity of nuclei isolated from human lymphocytes

Abstract 1. DNA-dependent RNA polymerase activity was studied in nuclei from human peripheral blood lymphocytes, incubated with and without phytohemagglutinin. Bivalent cation and (NH4)2SO4 requirements for maximum activity were the same in both resting and phytohemagglutinin-stimulated cells. 2. Nuclei obtained from lymphocytes incubated with phytohemagglutinin for 2–4 h showed an increased RNA polymerase activity in low salt (without (NH4)2SO4) but no increase over controls in high salt (0.4 M (NH4)2SO4). 3. Lymphocytes incubated for 20, 46, and 72 h with phytohemagglutinin had a progressive increase in RNA polymerase activity per nucleus in both high and low salt conditions. 4. The ratio of activity in high/low salt was consistently higher in resting than in phytohemagglutinin-stimulated cells. 5. The pattern of increased RNA polymerase activity in phytohemagglutinin-stimulated lymphocytes was essentially similar to that of regenerating liver cells and hormone-activated target cells in a number of systems.

Lead Intoxication in Children: Diagnosis and Treatment

Lead intoxication in children remains a source of continuing concern in both inner-city and suburban areas. Symptoms may be transient and often are erroneously associated with other childhood disorders. Since an elevated lead burden is not always obvious in routine laboratory determinations, a high degree of suspicion and use of the lead mobilization test described here are necessary for diagnosis. Prompt chelation therapy can prevent far-reaching behavioral and medical sequelae.

USE OF PENICILLAMIME IN LOW-LEVEL LEAD POISONING

We evaluated D-penicillamine (PCN) to determine its efficacy in low-level plumbism (25-40 mcg/dl). Two groups were compared: Cases (n=84) were treated with PCN; controls (n=37) received no chelation therapy. Patients were followed at regular intervals for a mean of 200 days; none had received chelation therapy for 3 months prior to study entry. Mean PCN dose was 27.5 mg/kg/d.In 64 cases (76%) lead levels (LL) were normalized. There were eight cases of treatment failure, Controls had no significant change in LL (mean LL 33± 2 mcg/dl) over the observation period. PCN was associated with an adverse reaction in 33%. Side effects included leukopenia in 10%, rash in 8%, enuresis in 4% and gastrointestinal distress in 2%. Therapy was prematurely terminated in 8 patients due to an adverse reaction. We conclude that PCN is effective therapy for low-level plumbism although it has significant side effects. PCN should be considered a viable treatment option for low-level lead poisoning.