Long-term effects of low-density lipoprotein apheresis using an automated dextran sulfate cellulose adsorption system. Liposorber Study Group.

The short-term effectiveness of low-density lipoprotein (LDL) apheresis using a dextran sulfate cellulose adsorption column technique was previously examined in a 9-center, 22-week controlled trial in 64 patients with familial hypercholesterolemia (FH) who did not adequately respond to diet and drug therapy. Forty-nine patients (40 treatment, 9 controls) subsequently received LDL apheresis procedures as part of an optional follow-up phase. This study reports on the long-term safety, lipid lowering, and clinical efficacy of LDL apheresis for the 5-year period that includes both the initial controlled study and follow-up phase. During this time, patients received a total of 3,902 treatments of which 3,314 treatments were given during the follow-up phase. Adverse events were infrequent, occurring in 142 procedures (3.6%). Immediate reduction in LDL cholesterol was 76% both in homozygotes and in heterozygotes. Patients with homozygous FH had a progressive decrease in pretreatment LDL cholesterol level along with an increase in high-density lipoprotein (HDL) cholesterol level. There was no appreciable change in pretreatment lipoprotein level over time in heterozygotes. The rate of cardiovascular events during therapy with LDL apheresis and lipid-lowering drugs was 3.5 events per 1,000 patient-months of treatment compared with 6.3 events per 1,000 patient-months for the 5 years before LDL apheresis therapy. These findings support the long-term safety and clinical efficacy of LDL apheresis in patients with heterozygous and homozygous FH who are inadequately controlled with drug therapy.

Serum aminotransferase elevation during and following treatment of childhood acute lymphoblastic leukemia.

PURPOSE: The clinical significance of methotrexate (MTX)-induced hepatic toxicity in children with acute lymphoblastic leukemia (ALL) is poorly defined. Therefore, we conducted a study to determine whether intensive MTX therapy could be safely delivered despite isolated serum ALT elevations in children with ALL. PATIENTS AND METHODS: A total of 243 children with B-precursor ALL were treated with extended pulses of oral divided-dose MTX (dMTX). Serum ALT levels were measured approximately every 7 weeks during therapy, as well as after its cessation. By protocol design, treatment was continued without modification in the presence of ALT elevations if there was no other evidence of liver dysfunction. RESULTS: Of 239 assessable patients, 159 (66.5%) had an ALT level > or = 180 IU/L during therapy and 28 patients (17.6%) had one or more values > or = 720 IU/L. After the completion of therapy, only 17 of 104 assessable patients have had one or more elevated ALT value. Eight of these 17 patients (47%) are hepatitis C virus (HCV)-seropositive. The remaining nine children had subsequent normal or near normal ALT values, and none have clinical evidence of liver disease. CONCLUSION: Our data show that MTX can be safely delivered without dose modification in patients with isolated ALT elevations and that continued therapy does not lead to clinically apparent liver disease. ALT elevations are not a reliable predictor of the presence or extent of hepatic injury, and persistently increased ALT values following the completion of ALL therapy are rare in the absence of HCV infection. Continued MTX therapy allows for increased dose-intensity and may improve outcome in children with ALL.

Azithromycin therapy for Cryptosporidium parvum infection in four children infected with human immunodeficiency virus.

Cryptosporidium parvum intestinal infection in immunodeficient patients can cause severe intestinal fluid losses with severe dehydration or chronic diarrhea with malnutrition. Therapies tried in human beings and animals include paromomycin, clarithromycin, azithromycin, octreotide, hyperimmune bovine colostrum, and bovine transfer factor. No specific therapy has been found to be consistently beneficial to children. We report azithromycin treatment of four children with acquired immunodeficiency syndrome who had severe diarrheal illnesses in which Cryptosporidium parvum was the sole pathogen detected. Three of these children had a marked decrease in stool volume and frequency within 36 hours of initiating therapy and resolution of diarrhea within 5 days; Cryptosporidium organisms became undetectable on examination of stool or colonic biopsy or by both after therapy was discontinued. A fourth patient required prolonged therapy with azithromycin to achieve clearance. Azithromycin therapy should be considered for immunocompromised patients with intestinal Cryptosporidium infection.

Follow-up after liver transplantation for protoporphyric liver disease.

Protoporphyria is a genetic disorder in which patients may develop severe protoporphyrin-induced liver damage and require transplantation. Because unique problems occur in the perioperative period and because excess production of protoporphyrin by the bone marrow continues after liver transplantation, the efficacy of this procedure for protoporphyric liver disease is uncertain. We present follow-up of nine patients who underwent liver transplantation. Two patients died within 2 months of transplantation, one from complications of abdominal bleeding and the other from sepsis after bowel perforations. The remaining seven patients had follow-up at 14 months to 8 years after transplantation (mean, 3.8 years). Two of the seven had suffered skin burns from exposure to operating room lights, which healed without scarring. Three had axonal neuropathies in the postoperative period requiring prolonged mechanical ventilation, and motor defects persisted in two. Five patients had normal liver chemistries at follow-up (mean, 3.5 years), with liver biopsy results normal or showing mild portal triad abnormalities, but erythrocyte protoporphyrin levels remained significantly elevated (1,765 +/- 365 mcg/dL; normal, < 65). The other two patients, both of whom had rejection, cytomegalovirus infection, and biliary tract obstruction requiring endoscopic therapy, had a recurrence of protoporphyric liver disease as indicated by liver biopsy features. One died 5 years after transplantation from complications of the liver disease. The other was stable 3.3 years after transplantation and was being monitored for possible retransplantation. Thus, liver transplantation can be performed successfully in patients with protoporphyric liver disease, with intermediate survival rates comparable to the general transplant population. However, disease may recur in the graft, particularly if there are complications that cause cholestasis.

Low-density lipoprotein apheresis as long-term treatment for children with homozygous familial hypercholesterolemia.

OBJECTIVE: To determine the safety and efficacy of long-term dextran sulfate-affinity column low-density lipoprotein (LDL) apheresis for the treatment of children with receptor-negative homozygous familial hypercholesterolemia (HFH). STUDY DESIGN: Two children with HFH (pretreatment cholesterol levels 22.1 to 24.7 mmol/L (ranges 850 to 950 mg/dl) began LDL apheresis treatments at ages 7 and 10 years, respectively. The LDL apheresis treatment interval was generally either 7 or 14 days; for the last 2 years of the study the treatment interval was 7 days. The patients had 167 and 188 LDL apheresis procedures during 64 and 70 months, respectively. RESULTS: Individual procedures decreased total blood cholesterol levels by 63% to 68%. When the treatment interval was 7 days, the patients' time-averaged mean total cholesterol levels decreased to 7.3 +/- 0.65 mmol/L (280 +/- 25 mg/dl) and 6.4 +/- 0.55 mmol/L (247 +/- 22 mg/dl), respectively. Both children remained clinically well with normal growth and development. There was significant regression of xanthomas in both patients. The older patient required heart surgery for preexisting aortic stenosis and coronary ostial stenosis, but neither patient had progression of hypercholesterolemia-related cardiovascular disease. With the exception of iron (deficiency in patient 1), there was no evidence of depletion of serum components. Adverse reactions to LDL apheresis were rare and never severe. CONCLUSIONS: Dextran sulfate-affinity column LDL apheresis is effective long-term treatment for children with receptor-negative HFH.

Use of distal splenorenal shunt in children referred for liver transplant evaluation.

Variceal bleeding remains a common cause of morbidity for children with both intrahepatic and extrahepatic portal hypertension. Occasionally, patients referred for liver transplant evaluation have significant variceal bleeding, despite adequate synthetic liver function. During a 7-year period, 322 children were referred for liver transplant evaluation. Six underwent distal splenorenal shunt surgery after evaluation. There were four boys and two girls. The average age was 11 +/- 4 years, and the average weight was 39 +/- 15 kg. The etiology of variceal bleeding was intrahepatic portal hypertension in five (1 biliary atresia, 2 chronic hepatitis, 2 congenital hepatic fibrosis) and extrahepatic portal vein thrombosis in one. Two patients had no previous attempts at sclerotherapy (one because of an abnormality in platelet function, the other because of extensive gastric varices), and four had multiple previous sclerotherapy treatments. No patient had preoperative encephalopathy. Three cases were Child's class A, and three were Child's class B. Preoperative evaluation of the portasystemic system was performed with magnetic resonance (MR) imaging or splenoportography. All patients underwent a distal splenorenal shunt procedure, four of whom also had splenopancreatic disconnection. One patient required 100 mL of blood replacement, and five required no blood. The average length of hospital stay was 9.8 +/- 2.2 days. Postoperative complications were minimal. All patients are alive, without recurrent gastrointestinal bleeding or encephalopathy, and they have patent shunts, which was confirmed by MR or Doppler ultrasound at a mean of 25 +/- 20 months after shunt surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Chronic hepatitis B in adopted Romanian children.

Four of five Romanian orphans adopted by U.S. families were found to have chronic hepatitis B virus (HBV) infection after negative test results were reported in Romania before adoption. Another child with known HBV infection was found to be coinfected with hepatitis D virus. There is a high incidence of HBV infection in Romanian orphans, and results of tests for HBV are unreliable in Romania.

Treatment of children with homozygous familial hypercholesterolemia: safety and efficacy of low-density lipoprotein apheresis.

We evaluated the safety and efficacy of dextran sulfate low-density lipoprotein (LDL) apheresis in the treatment of three children (aged 6, 7, and 10 years) with severe familial homozygous hypercholesterolemia and undetectable LDL receptor activity. A total of 35 double plasma volume procedures were performed. The ranges of the mean decreases of the three patients in plasma lipid concentrations after LDL apheresis (p less than 0.0001) were as follows: total cholesterol, 76% to 79%; LDL-cholesterol, 78% to 81%; very low density lipoprotein cholesterol, 69% to 75%; high-density lipoprotein cholesterol, 27% to 40%; and triglycerides, 34% to 68%. There were statistically significant but clinically and biologically irrelevant changes in hematologic indexes, serum chemistry values, immunoglobulin levels, complement activity, and plasma concentrations of fat-soluble vitamins. Simple correlation analysis of the variables affecting total cholesterol removal showed significant correlation coefficients (r values) for preapheresis total cholesterol values (r = 0.70; p less than 0.01) and preapheresis LDL-cholesterol values (r = 0.61; p less than 0.01). A multiple regression model explained 82% of the variance based on the preapheresis cholesterol concentration, volume of whole blood processed, and the serum albumin concentration. Side effects of the LDL-apheresis treatments were rare and included abdominal cramping and urticaria. Two procedures were aborted because of intravenous access problems in the younger children. This study confirms that LDL apheresis using a dextran sulfate affinity column is efficacious in rapidly lowering total and LDL-cholesterol concentrations. Furthermore, the procedure is safe and well tolerated by children as young as 6 years of age. This treatment may prevent the progression of atherosclerosis in children with homozygous familial hypercholesterolemia and may therefore avert early death.

Severe pseudomembranous enterocolitis in a child: case report and literature review.

Antibiotic-associated pseudomembranous enterocolitis (PMC), an inflammatory gastrointestinal disease mediated by toxins produced by Clostridium difficile, is increasingly recognized in the pediatric population. We report a case of fulminant PMC in an otherwise normal 2 1/2-year-old child after antibiotic therapy given for a routine childhood illness. The patient had debilitating colitis marked by severe diarrhea, a generalized electrolyte derangement, an extreme protein-losing enteropathy state, rectal prolapse, ascites, pleural effusion, varicella and multiple relapses. The child required specific antimicrobial therapy as well as aggressive supportive care to achieve recovery. A review of the literature for pediatric cases of PMC revealed reported cases in all age groups; the youngest was 5 days old. There were 9 deaths in 43 cases for a mortality rate of about 20%. All but 2 of the cases were associated with antibiotic therapy. The antibiotics most frequently implicated were ampicillin (15), penicillin (11), cephalosporins (7), amoxicillin (6) and clindamycin (5). The onset of symptoms of PMC can begin at any time while the child is taking an antibiotic or up to 21 days after it is discontinued. Children with underlying gastrointestinal motility disorders such as Hirschsprung's disease are predisposed to PMC. Fulminant PMC is a serious but uncommon infectious disease of infancy and childhood, occurring as a complication of routine antibiotic therapy for common childhood illnesses.

Organophosphate and carbamate poisoning in infants and children.

The clinical and laboratory features of moderate to severe organophosphate and carbamate toxicity in 37 infants and children are presented. Ingestion of an improperly stored liquid pesticide was the most common route of intoxication (76% of patients); five (14%) children became intoxicated after playing on carpets and floors of homes that had been sprayed or fogged by unlicensed exterminators. The transfer diagnoses were incorrect for 16 or 20 patients who were transferred to our center from another institution. Miosis (73%), excessive salivation (70%), muscle weakness (68%), and lethargy (54%) were the most common abnormal signs; 49% and 22% of patients had tachycardia and seizures, respectively, and 38% of children had respiratory insufficiency that required endotracheal intubation and mechanical ventilation. The results of erythrocyte and serum cholinesterase activity assays were concordant in 83% of patients. Thirty-four (92%) patients were treated with atropine and/or pralidoxime; three patients required only supportive care. Most patients had a prompt response to therapy; however, two patients with organophosphate toxicity required multiple doses of atropine during a 24-hour period; in both instances, the doses of atropine were subtherapeutic. There were no deaths. Pneumonitis and/or atelectasis developed in ten patients, including six who had ingested a petroleum distillate-containing insecticide.