Involuntary movements in infantile cobalamin deficiency appearing after treatment.

Involuntary movements may be a symptom in most infants who present with neurologic syndrome of infantile cobalamin (vitamin B12) deficiency. In this report, two infants with cobalamin deficiency are presented. These patients also developed a striking movement disorder that appeared a few days after treatment with intramuscular cobalamin. The movement disorder was characterized by severe involuntary movements, which were a combination of tremor and myoclonus particularly involving tongue, face, pharynx, and legs. The neurologic symptoms improved within a few days after the administration of clonazepam. In each patient the mother was also cobalamin deficient and the infant was solely breast-fed. The cause of involuntary movements that can appear rarely after treatment in infantile cobalamin deficiency is not known. Besides initial neurologic presenting symptoms of cobalamin deficiency, the occurrence of involuntary movements after treatment should also receive attention. This movement disorder may disappear spontaneously, or an additional treatment may be an alternative approach if the symptoms are severe.

Oral cyclic megadose methylprednisolone therapy for chronic immune thrombocytopenic purpura in childhood.

The objectives of this study were to investigate the effectiveness of oral megadose methylprednisolone (OMMP) therapy in children with chronic immune thrombocytopenic purpura (ITP). Twenty-two patients were given oral methylprednisolone daily for 7 d (30 mg/kg for 3 d and then 20 mg/kg for 4 d). OMMP therapy was repeated once per month if the platelet count was less than 20,000/mm3 at the 30th day of therapy, for up to six courses. The number of platelets of all patients increased gradually during the OMMP therapy, with a peak number at the 7th day, then decreased until the 14th day, and remained relatively stable until 12 months. During the study no patient had a platelet count less than 20,000/mm3 at the 3rd day and 50,000/mm3 at the 7th day. Although the number of platelets was gradually decreased between the 7th and 14th days, it remained above 100,000/mm3 for at least 12 months in the nine patients, and above 20,000/mm3 in the four patients. None of these 13 patients required hospitalization or therapy during the follow-up period. All of the patients tolerated the medication well. None of them reported side-effects that were severe enough to discontinue therapy. We conclude that OMMP therapy is a safe, easy and effective therapy in children with refractory chronic ITP, and it may provide long-term remission in about two thirds of the patients.

Efficacy of interferon-alpha2b treatment in children with chronic hepatitis B who have previously undergone therapy for cancer.

BACKGROUND: The aim of the present study was to evaluate the efficacy of treatment with recombinant interferon (IFN)-alpha2b in 12 children with chronic hepatitis B who had previously undergone therapy for cancer. METHODS: Nine children had acute leukemias and the other three children had solid tumors. The mean (+/-SD) age of the children was 8.4+/-3.8 years (range 4-16 years). All cases were hepatitis B virus (HBV)-DNA positive and 11 were hepatitis B e antigen (HBeAg) positive. One was anti-HBe positive (mutant strain). Four cases were anti-delta IgG positive. Liver biopsy revealed chronic hepatitis B in 11 patients and cirrhosis in one patient. Interferon-alpha2b was given at a dose of 5 MU/m2 three times a week, subcutaneously, for 12 months. RESULTS: Elimination of serum HBV-DNA was obtained in three cases, but a further three patients demonstrated a marked decrease in HBV-DNA levels after therapy. Three of 11 patients seroconverted from HBeAg to anti-HBe. Alanine aminotransferase (ALT) levels returned to normal in three of nine cases in whom the ALT levels were high before treatment. At the end of therapy, the mean histologic activity index score was significantly diminished (P = 0.0039). CONCLUSIONS: In conclusion, a 12 month course of IFN-alpha2b induces some beneficial effects on virologic, biochemical and histologic indices in children with chronic hepatitis B who have previously undergone therapy for cancer.

Hepatic expression of viral antigens, hepatocytic proliferative activity and histologic changes in liver biopsies of children with chronic hepatitis B after interferon-alpha therapy.

AIMS/BACKGROUND: The purpose of the present study was to evaluate the effects of interferon-alpha (IFNalpha) treatment on necro-inflammatory changes, viral antigen expression and hepatocytic proliferation rate assessed by Ki-67 protein in liver biopsies of children with chronic hepatitis B virus (HBV) infection. METHODS: The study included 18 children at prepubertal age. Histologic changes were assessed using a modified scoring system for grading of histological activity index and staging of fibrosis. The hepatocytic expression of Ki-67 and HBV antigens including HBV surface antigen (HBsAg) and HBV core antigen (HBcAg) were evaluated using a semi-quantitative immunohistochemical scoring system. RESULTS: We found a significant decrease in the scores of intralobular confluent and spotty necrosis, periportal piecemeal necrosis, and in Ki-67 immunopositivity after treatment. Serologic response with clearance of HBV e antigen in 9 patients (50%) was associated with this improvement. The extent of fibrosis and scoring of portal inflammation, however, did not show any difference. HBcAg expression showed a significant decrease after treatment, whereas HBsAg expression either increased or remained unchanged. CONCLUSION: We conclude that IFNalpha treatment might provide an improvement in hepatic histology with a reduction in hepatocytic injury. It might also provide a serologic response associated with a decrease in hepatocytic HBV replication.

Factor VIII inhibitors in patients with hemophilia A.

In 58 hemophilia A patients aged 1-18 years (mean 9.5 +/- 4.7 years), the prevalence of inhibitors was found to be 27% by the Bethesda method in November 1995. Inhibitor activity was not detected in any of 14 patients with mild hemophilia while it was present in 9 of 27 (33%) patients with moderate, and 7 of 17 (41%) with severe disease. During follow-up, the inhibitors were transient in 10 of 16 patients (17%) and the prevalence of inhibitors was 10% at the end of the study. Our study has demonstrated that the patients' age, factor VIII (F VIII) coagulant activity levels, type of F VIII replacement therapy, and frequency of F VIII administration affect inhibitor development, and these factors should be considered in the follow-up of hemophiliacs.

Efficacy of interferon therapy on serum fibronectin levels in children with chronic hepatitis B infection.

BACKGROUND: Fibronectin (FN) is a glycoprotein, the major sources of which are hepatocytes, Kupffer cells and endothelial cells. It has many biological functions including adhesion between cells, immunity, blood coagulation and platelet aggregation. Serum FN levels are generally decreased in pathological blood coagulation and inflammation. In the present study, we evaluated the serum levels of FN in patients with chronic hepatitis B virus (HBV) infection treated with interferon-alpha 2b. METHODS: We studied serum levels of FN in a prospective trial between October 1995 and May 1997. The study included 16 patients with chronic HBV infection before and after interferon therapy, in a period of 6 months, and 17 healthy controls. In total, we had 40 patients with chronic HBV infection. We studied these 16 patients (40%) who recovered with interferon therapy. We could not study the other 24 patients because we did not have enough of the reagents for studying FN. RESULTS: Chronic hepatitis B infection was diagnosed serologically and histopathologically. In mean age and sex, no statistically significant differences were found between patients and healthy subjects. The serum FN concentration before treatment with interferon therapy appeared significantly lower in HBV patients than in healthy control subjects (P = 0.026 using the Mann-Whitney confidence interval and test). After treatment with interferon, serum levels of FN were significantly higher than levels obtained before interferon therapy (P = 0.004 using the Wilcoxon Test). CONCLUSIONS: These results suggest that a decreased level of serum FN in patients with chronic hepatitis before interferon treatment is related to hepatic injury and inflammation. Because of inflammation, the serum FN level is decreased due to the consumption of FN. Increased levels of serum FN in patients having interferon therapy is important and is related to the effects of interferon including antiviral, antiproliferative, anti-inflammatory and immunoregulatory properties in patients with chronic HBV infection. A Japanese study showed a correlation between development of hepatic fibrosis and decrease of plasma FN concentration in adult patients with chronic liver disease. Therefore, the serum level of FN may be a useful marker of hepatic fibrosis in chronic liver disease and interferon may be an important drug for prevention of liver fibrosis. Fibronectin may be also a useful marker in predicting IFN response.

Left ventricular diastolic abnormalities in children with beta-thalassemia major: a Doppler echocardiographic study.

Left ventricular filling patterns were assessed by Doppler echocardiography in 63 beta-thalassemia major patients, aged for to 21 years, with no clinical evidence of congestive heart failure and 63 age- and sex-matched normal controls. The patients with beta-thalassemia major were divided into three age groups, namely four to nine years (6.8 +/- 1.5 years), 10-15 years (12.1 +/- 1.6 years) and older than 15 years (17.3 +/- 1.7 years). They were compared with age- and sex-matched normal controls in respects of Doppler diastolic indices. The ratio between the early and late (atrial) peaks of flow velocity was higher and peak flow velocity in late diastole was significantly lower in patients with beta-thalassemia major as compared to controls in all three age groups (p < .001). As compared with the controls, peak early diastolic flow velocity was also significantly higher in the thalassemics aged 10 to 15 years (92 +/- 16 vs 80 +/- 12 cm/s, P < .01) and in those older than 15 years (95 +/- 16 vs 79 +/- 13 cm/s, p < .001). Restrictive left ventricular diastolic abnormalities were detected in a total of 34 (54%) patients with beta-thalassemia major, whereas left ventricular systolic abnormalities were identified only eight (13%) of them. None of the patients without left ventricular diastolic abnormalities showed left ventricular systolic abnormalities. There was not any significant correlation between the hematologic parameters, such as mean serum ferritin, maximum serum ferritin and the number of blood units transfused, and left ventricular Doppler diastolic indices (p > .05). From the data presented here, we therefore conclude that left ventricular diastolic abnormalities develop in patients with beta-thalassemia major in the early phase of the disease and before the appearance of systolic abnormalities, when clinical symptoms of congestive heart failure are absent.

A comparison of different filters for white cell reduction.

Removal of white blood cells (WBCs) from blood components before transfusion by filters with at least 3 log10 depletion may prevent or delay leukocyte-associated transfusion reactions such as HLA alloimmunization, non-hemolytic febrile reactions, transmitted infections (e.g., CMV, HTLV-1), and immunomodulation. The aim of this study was to compare the leukocyte removal efficiency (LRE) of six commercial bedside filters that are said to achieve 3 log10 (Bio R-01), Leucostop 4LT-1, Pall RC 50) and 4 log10 (Bio R-01 Plus, Pall RC 400, Pall RC XL-1) WBC depletion. A total of 430 units of whole blood ranging from 32 to 92 for each filter type were analyzed by an automated counter before and after filtration. Postfiltration blood samples were also evaluated for WBCs by Nageotte chamber. All the filters demonstrated leukocyte removal about 1 log10 less than the manufacturer's claim. The fourth generation filters showed a better performance than the third generation filters. Of them, Pall RC XL-1 showed the best efficacy with 99.93 percent leukocyte removal and a median residual WBCs of 1.6 x 10(6) per unit. These results indicate that the fourth generation filters, which are designed for the filtration of packed red cells, in particular Pall RC XL-1, are also able to reduce WBCs from whole blood below the critical antigenic leukocyte load (5 x 10(6)), and can be efficiently used for polytransfused patients to prevent alloimmunization.

Insulin secretion and insulin resistance determined by euglycemic clamp.

Obesity among children is increasingly recognized and linked to several metabolic problems. In this study, 47 children, aged 5-14 yr, with exogenous obesity were compared to 20 normal (non-obese) children to show alterations in glucose metabolism. All the obese children had body mass index > 95th percentile and weight for age > 120%. Basal and stimulated insulin and C-peptide levels were obtained during oral glucose tolerance test (OGTT). Seven children from the obese group had impaired OGTT according to WHO criteria. Mean fasting insulin levels were 26.7 +/- 14.6 microIU/ml in obese and 10.99 +/- 4.36 microIU/ml in controls; postprandial insulin levels were 70.4 +/- 56.4 microIU/ml and 22.23 +/- 6.55 microIU/ml, respectively (p < 0.001). The euglycemic glucose clamp technique was applied to 8 normal and 22 obese children. The amount of metabolized glucose (M) during clamp test is measured to identify glucose sensitivity. Mean M values were 3.24 +/- 1.35 mg/kg/min in obese and 6.525 +/- 0.770 mg/kg/min in control children (p < 0.001). As a result of this study, it seems reasonable to consider all obese children and adults as being at risk for hyperinsulinism and insulin resistance.

Carob bean juice: a powerful adjunct to oral rehydration solution treatment in diarrhoea.

In children, the treatment of acute diarrhoea with the World Health Organization (WHO) standard oral rehydration solution (ORS) provides effective rehydration but does not reduce the severity of diarrhoea. In community practice, carob bean has been used to treat diarrhoeal diseases in Anatolia since ancient times. In order to test clinical antidiarrhoeal effects of carob bean juice (CBJ), 80 children, aged 4-48 months, who were admitted to SSK Tepecik Teaching Hospital with acute diarrhoea and mild or moderate dehydration, were randomly assigned to receive treatment with either standard WHO ORS alone or a combination of standard WHO ORS and CBJ. Three patients were excluded from the study because of excessive vomiting. In the children receiving ORS + CBJ the duration of diarrhoea was shortened by 45%, stool output was reduced by 44% and ORS requirement was decreased by 38% compared with children receiving ORS alone. Weight gain was similar in the two groups at 24 h after the initiation of the study. Hypernatraemia was detected in three patients in the ORS group but in none of those in the ORS + CBJ group. The use of CBJ in combination with ORS did not lead to any clinical metabolic problem. We therefore conclude that CBJ may have a role in the treatment of children's diarrhoea after it has been technologically processed, and that further studies would be justified.

Comparative efficacy of cefixime and ampicillin-sulbactam in shigellosis in children.

Shigellosis is still an important health problem in developing and underdeveloped countries as it is resistance to commonly used antibiotics including ampicillin, trimethoprim-sulfamethoxazole, chloramphenicol and tetracycline. Between May 1996 and October 1996, in a prospective randomized double-blind trial, cefixime was compared with ampicillin-sulbactam, both given orally for a period of 5 days, for the treatment of 80 children with acute bloody diarrhea. Forty patients were treated with a single-dose (8 mg/kg per day) of cefixime and the other 40 patients were given three doses of 100 mg/kg per day of ampicillin-sulbactam. After identification of Shigella organisms in stool specimens, nine patients in the cefixime receiving group and six patients in the ampicillin-sulbactam receiving group were excluded from the study. Differences in average age, sex and weight between the cefixime and ampicillin-sulbactam group were statistically meaningless (P > 0.05). Fever and bloody diarrhea were universal features. The efficacy of cefixime was found to be better than ampicillin-sulbactam. Patients given cefixime had a shorter duration of fever (P < 0.01), shorter duration to disappearance of blood in the stool (P < 0.01), reduced time with diarrhea (P < 0.01) and reduced hospitalization time during the 5 study days (P < 0.01) than patients given ampicillin-sulbactam. No adverse effects were observed in the two study groups. This controlled trial showed good efficacy with cefixime compared to ampicillin-sulbactam in the treatment of shigellosis. Single-dose daily oral therapy with cefixime also showed good tolerability. Cefixime should be considered as an alternative drug of choice for shigellosis in children.

Psychosocial aspects and psychiatric disorders in children with thalassemia major.

beta-thalassemia major (TM), a chronic, genetically determined hematological disorder, has received little investigation on the psychological aspects of the disease and the psychosocial adjustment of patients with this anemia. In the present study, the aim was to assess the mental capacity, self-image, hopelessness and anxiety displayed by children who suffered from TM, and to investigate the existence of psychiatric disorders in these children. Twenty-five children (16 boys and 9 girls) with TM, 12.0-19.6 years old, from the Hematology Unit of the Department of Pediatrics at the SSK Tepecik Teaching Hospital, were included in the study. Fifteen healthy cases matched for age, sex and socio-economic status were used as controls. The Wechsler Intelligence Scale for Children (or Wechsler Adult Intelligence Scale), Offer Self-Image Questionnaire, Beck Hopelessness Scale, Trait Anxiety Inventory, Symptom Check List (revised) and the Family Assessment Device were performed on all patients. Then, the patients were evaluated for a psychiatric disorder by a psychiatrist (according to the diagnostic criteria of the Diagnostic and Statistical Manual IV of the American Psychiatric Association). The results for the patients and control cases were compared statistically using Mann-Whitney and Kruskal-Wallis tests. Self-image was found to be significantly lower in patients with TM than in control cases (P < 0.01). Hopelessness and Trait-Anxiety scores were determined to be significantly higher in patients with TM than in control cases (P < 0.01 and P < 0.05, respectively). Eighty percent of the patients with TM have had at least one psychiatric disorder. As a result, the study showed that most of the patients with TM had severe psychosocial problems. Relying on these data, it was concluded that medical therapy of these patients should be supported with psychological aid and psychiatric treatment.

Evaluation of sponging and antipyretic medication to reduce body temperature in febrile children.

Two hundred and twenty-four children aged 6 months to 5 years, with rectal temperatures greater than or equal to 30 degrees (104 degrees F), were randomly treated with sponging alone or with medication including a single oral dose of aspirin 15 mg/kg, or paracetamol 15 mg/kg, or ibuprofen 8 mg/kg. Twenty-three children were excluded from the final analysis because they did not complete the study. Demographic characteristics of the patients were found to be comparable in all groups. Rectal temperatures were recorded every 30 min for a 3 h period. During the first 30 min of intervention, sponging was found to be more effective than all of the three medications. After 60 min, the effects of each medication became superior to sponging with tepid water in reducing body temperature. Twenty-three children were excluded from the final analysis because they did not complete the study. Comparing the effect of the three different medications, it was seen that the antipyretic efficacy of aspirin and ibuprofen were significantly more than paracetamol 3 h after intervention (P < 0.05). For the management of fever over 39 degrees C, it is therefore recommended to give children an antipyretic drug, preferably ibuprofen, and at the same time to begin sponging to provide a rapid and sustained antipyresis

Aflatoxin: is it a neglected threat for formula-fed infants?

In the present study, the risk of exposure to aflatoxin in infants fed breast milk and formula was investigated. For this purpose, aflatoxin B1 (AFB1) was determined in the serum of both breast-fed and formula-fed infants. Serum AFB1 positivity was significantly higher in the formula-feeding (F) group than the breast-feeding (B) group (42.8 vs 8.5%, P < 0.01). The AFB1 concentration in different commercial formulas was also determined. Aflatoxin B1 was found in seven of the eight newly opened packages of different brands of formula. The concentrations showed a statistically significant increase at the 30th day after opening the packages (P < 0.01). Although AFB1 concentrations in the formulas were found to be within acceptable limits for most countries, still, its existence must be carefully evaluated because future influences of very small amounts of aflatoxin on the growing organism have not been fully elucidated. Therefore, it was again concluded that for infants, human milk is safer than commercial formulas because of the lower contamination risk of aflatoxin. Also, commercial formulas must be regularly examined by authorities for the possible risk of aflatoxin contamination.

Long-term use of anti-D in chronic idiopathic thrombocytopenic purpura.

Chronic idiopathic thrombocytopenic purpura is an autoimmune disease characterized by antibody-mediated destruction of platelets. To maintain the platelets above the symptomatic level, we administered anti-D (100 micrograms for 5 consecutive days) in 19 children with idiopathic thrombocytopenic purpura (ITP). Four patients did not respond to treatment. Fifteen responded with an increase in the average platelet number to 76,000/microL on the 7th postinjection day. Within 45 days, however, platelets dropped to 27,000/microL. Three months after this study, two patients from the study group were re-administered anti-D in daily injections for 5 consecutive days, as was done previously. Monthly administration of anti-D in two patients maintained platelets above 30,000/microL for periods of five and six months. We concluded that monthly administration of anti-D after five consecutive daily injections can maintain platelet levels above the symptomatic level and may provide a corticosteroid-free safe interval of nearly five months.

The decline of BCG immunity after neonatal vaccination: what about revaccination at one year?

Two hundred and nineteen healthy newborns were vaccinated with the BCG vaccine, and their immunity was checked thereafter at 3, 6 and 12 months of age. We determined that 87% of tuberculin reactivity at 3 months declined to 61% at 12 months. Revaccination of nonreactive infants provided a 100% rate of reactivity. In the light of this information we propose a revision in the BCG vaccination programme in developing countries. We also found a close relationship between the tuberculin reactivity and scar formation after BCG vaccination, suggesting that a simple check of the left deltoid region for a BCG scar may give enough information about the child's immunity to tuberculosis.

Superiority of oral agar and phototherapy combination in the treatment of neonatal hyperbilirubinemia.

OBJECTIVE: To determine the value of oral agar in the treatment of neonatal hyperbilirubinemia and to compare it with two other treatment modalities: phototherapy alone and phototherapy plus oral agar. METHODS: Two hundred eight jaundiced full-term newborns were divided into four groups. They were given either phototherapy alone, phototherapy plus oral agar, oral agar alone, or no treatment (control group). The changes in the serum bilirubin values were determined and the results were compared statistically, mainly using analysis of variance. RESULTS: In all three therapy groups, the time required to reduce the bilirubin level to either 15 mg/dL or to 10 mg/dL was significantly shorter than that required by the control group. Although oral agar was found to be as effective as phototherapy, the most significant decrease in bilirubin level was in the combination group. CONCLUSIONS: The efficacy of phototherapy in decreasing the serum bilirubin level in neonatal hyperbilirubinemia can be augmented with the use of oral agar. Oral agar can also be used as a single agent for the treatment of neonatal hyperbilirubinemia, since it is as effective as phototherapy.

Disappearing intracardiac thrombi in both atria after mumps in a patient with Turner syndrome.

A girl with Turner syndrome was admitted with an acute cerebrovascular occlusive disease 15 days after mumps infection. Imaging techniques such as Doppler echocardiography, computed tomography and angiography of the heart revealed the existence of masses in both atria. Eight days after the last radiologic study the patient had an operation, but no masses were found in either atrium. It was thought that atrial thrombi, probably formed after viral infection, had broken down to form emboli and disappeared. It is proposed that the patients with congenital cardiopathy should be regularly examined after viral infections for possible intracardiac thrombus formation. If such a mass is found and the decision is to operate, the existence of the mass must be confirmed even in the operating room just before intervention.

Steroid-free interval with anti-D in chronic idiopathic thrombocytopenic purpura.

Chronic idiopathic thrombocytopenic purpura (ITP) is an autoimmune disease characterized by the antibody-mediated destruction of platelets. To maintain the platelets above the symptomatic level we administered 100 micrograms of anti-D for 5 consecutive days to 19 children with ITP. Four patients did not respond to the treatment. Fifteen responded with an increase in the average platelet number to 76,000/microL 7 days postinjection. However, the platelet count dropped within 45 days to 27,000/microL. Three months after this study, two patients from the study group were then administered monthly anti-D after reinjecting anti-D daily for 5 consecutive days, as previously performed. Platelet levels in these two patients were maintained above 30,000/microL for 5 and 6 months respectively. We concluded that anti-D administration for 5 consecutive days can induce an increase in platelets followed by a decrease below 30,000/microL after 30-45 days. However, monthly administration of anti-D after daily injections for 5 consecutive days can keep platelets above the symptomatic level and may provide a corticosteroid-free safe interval for nearly 5 months.