The role of Epstein-Barr virus in Hodgkin's disease from different geographical areas.

Recent studies have suggested that Epstein-Barr virus (EBV) may play a role in the aetiology of Hodgkin's disease. To determine the role of EBV in childhood Hodgkin's disease in different geographical areas, immunohistochemical staining and in situ hybridisation were used to analyse latent membrane protein 1 (LMP 1) and small nuclear non-transcribed RNAs (EBER-1) respectively. Testing for EBV within the Reed-Sternberg and Hodgkin's cells was carried out in childhood Hodgkin's disease from 10 different countries. The proportion of LMP 1 positive cases varied significantly, being 50% of cases from the United Kingdom (38/75), South Africa (9/18), Egypt (7/14), and Jordan (8/16), 60% from the United Arab Emirates (6/10), 70% from Australia (11/16), 81% from Costa Rica (34/42), 88% from Iran (7/8), 90% from Greece (20/22), and 100% of the 56 cases from Kenya. A sensitive polymerase chain reaction based EBV strain typing technique was established using archival tissues. EBV strain type 1 was shown to be predominant in childhood Hodgkin's disease from the United Kingdom, South Africa, Australia, and Greece. Type 2 was predominant in Egypt. EBV strain types 1 and 2 were both detected in some cases of childhood Hodgkin's disease in the United Kingdom, Costa Rica, and Kenya. The high incidence of EBV and the presence especially in developing countries of dual infection with both strain types 1 and 2 may reflect socioeconomic conditions leading to malnutrition induced immunological impairment. The possibility of HIV infection also needs to be explored.

Red cell aplasia resembling Diamond-Blackfan anemia in seven children in a family.

PATIENTS AND METHODS: Seven children of the same family with a possible variant of Diamond-Blackfan anemia (DBA) are reported. Five were male siblings, and the other two were their cousins, one male and one female. All were products of consanguineous marriages of healthy parents. All cases occurred within one generation. Anemia was present at birth or shortly after birth. Hepatosplenomegaly was present in all. Four had short stature. Hematological findings included normochromic, normocytic, or macrocytic anemia, marked reticulocytopenia, with initial normal white blood cell and platelet count, and absent or markedly decreased erythroid precursors on bone marrow examination. All were treated initially with prednisolone; in one patient oxymetholone was added. RESULTS: Three children failed to respond to the initial treatment, and also failed to respond to cyclosporin A and pulse doses of methylprednisolone. Myelofibrosis occurred in two siblings, 9 and 11 years from diagnosis. In two children the disease recurred 9 and 12 years after initial diagnosis. CONCLUSIONS: Our cases point to a possible variant of DBA characterized by the presence of normochromic normocytic anemia, hepatosplenomegaly, absent skeletal malformations, and unusual long- term complications.

Congenital malignant melanoma of the eye.

Twenty-three cases of congenital malignant melanoma have previously been reported. Here the authors report the first case of a congenital malignant melanoma arising in the eye. A newborn girl had a large pigmented ocular tumor, hepatomegaly, and multiple pigmented skin and choroidal lesions. The histopathologic diagnosis was of a malignant melanoma with hepatic metastases. The skin and choroidal lesions were considered to be congenital melanocytic nevi. The most plausible pathogenetic link between these two conditions was that the malignancy had arisen as a second-hit mutation within a choroidal congenital melanocytic nevus. Despite widespread metastases the baby, treated by surgery and chemotherapy, survives in good health, aged 2 years, 10 months.

Homozygous protein C deficiency with delayed onset of symptoms at 7 to 10 months.

We report an inbred family with two cases of homozygous protein C deficiency and review 11 other such cases. Both patients presented in the second half of their first year of life with recurrent rapidly disappearing ecchymotic skin lesions, disseminated intravascular coagulation, and venous thrombosis. Successful treatment has been achieved by frequent infusions of plasma or prothrombin complex then maintained with Warfarin. Homozygous recessive protein C deficiency usually presents in the neonatal period with purpura fulminans. Two cases have been described elsewhere which presented in the second decade of life with milder symptoms. The present cases appear to be intermediate in time of presentation and severity of symptoms. We also review the distinction that is now evident between recessive and dominant protein C deficiency.

MOPP therapy in children with Hodgkin's disease.

Between 1979 and 1987, 28 children with Hodgkin's disease were treated with MOPP (nitrogen mustard, Oncovin, prednisone, procarbazine) combination chemotherapy without radiotherapy. Twenty-four were staged clinically. Splenectomy was performed in four only. Staging was as follows: nine (32%) in stage I, five (18%) in stage II, nine (32%) in stage III, and five (18%) in stage IV. Histologic types were lymphocytic predominance in five (18%), mixed cellularity in 15 (54%), nodular sclerosis in seven (25%) and lymphocytic depletion in one (4%). All children achieved complete remission. Two in stages III and IV relapsed and were salvaged with additional chemotherapy and radiotherapy. Twenty-six are in continuous relapse-free remission for periods ranging from 2 to 9 years. The relapse-free survival rate of 92% and survival rate of 100% compares favorably with results obtained using combined modality treatment.

Pharmacokinetics of high and moderate intravenous doses of methotrexate.

The pharmacokinetic parameters of methotrexate in nine cancer patients receiving 250-2500 mg/day were investigated. Both elimination rate constants and half-lives were calculated using a two-compartmental open model. The plasma levels-time profiles revealed a biphasic response with a mean initial elimination half-life of 2.3 +/- 0.2 hours and a terminal elimination half-life of 32.2 +/- 7.2 hours.

Effects of food and gender on the pharmacokinetics of methotrexate in children.

The effects of food and gender on the oral absorption of methotrexate (MTX) in 16 Jordanian children were investigated. Plasma levels of MTX were measured by a fluorescence polarization immunoassay. The extent of absorption and the rate of elimination of the drug were determined in both males and females, before and after meals and data were statistically analyzed using two-way analysis of variance. The results showed great variability in individual MTX Cmax, t1/2, Kel. and AUC. Although no statistically significant differences were found in the pharmacokinetic parameters of the drug among the groups, apparent differences were observed in the mean values of these parameters.

Burkitt's lymphoma in Jordanian children: epidemiological and clinical study.

Twenty-four children with a diagnosis of Burkitt's lymphoma were seen at Jordan University Hospital during a 6 year period (1978-1983). Their median age was 4 years and the male to female ratio was 3:1. A space clustering of cases was evident. Abdominal mass was the commonest presentation being observed in 21 patients, while only two patients presented with jaw masses. Sixteen patients had advanced disease (stages C and D). Chemotherapy was the basic form of therapy given. Twelve children (50%) survived. Advanced stage and poor nutritional status at diagnosis correlated with poor outcome. Our data indicate that Burkitt's lymphoma in Jordanian children presents an intermediate type that shares some similarities with both the endemic (African) and non-endemic types.

Mixed mesodermal tumor of the uterus in a 4-year-old girl.

A case of malignant mixed mesodermal tumor (MMT) of the uterus in a 4-year-old girl is reported. The patient had a polypoid lesion protruding from the vagina which was initially thought to be a sarcoma botryoides. This is one of the youngest cases of MMT on record. A review of MMT in premenopausal women and children is presented.

Hodgkin's disease in Jordanian children: a study of 26 cases.

A retrospective review of Hodgkin's disease in 26 children of 14 years of age and below admitted to Jordan University Hospital during the period from 1976 through 1981 was conducted. This review showed a preponderance of males, particularly in the first decade of life, with prominence of the prognostically unfavourable histologic sub-types and advanced clinical stages.

Serum ferritin in evaluation of iron status in children.

The value of serum ferritin in assessing iron status was studied in 192 preschool age children between the ages of 3 and 60 months. Children were considered to have iron deficiency if the transferrin saturation was less than 16% and the peripheral smear revealed microcytosis and hypochromia. Anemia was present when hemoglobin level was 10.5 g/dl. According to this criteria, 46% of children screened had either iron deficiency (11.5%) or iron deficiency anemia (34.4%). Mean serum ferritin for the iron deficiency anemia group was 39.1 ng/mg as compared to 41.7 ng/ml for the iron deficiency group and 84.7 ng/ml for the normal group. Even though the serum ferritin level was lower in the iron deficiency group, the difference in the means did not reach statistical significance. Furthermore, only 30% of children who had either iron deficiency or iron deficiency anemia had serum ferritin level of less than 12 ng/ml, the level considered diagnostic for iron deficiency. It can be concluded that serum ferritin cannot be used alone for iron status determination. Multiple parameters will make the assessment more reliable.

Improved survival in young children with acute granulocytic leukemia treated with combination therapy using cyclophosphamide, oncovin, cytosine arabinoside, and prednisone.

Seven of 17 children (41%) under 5 years of age with acute granulocytic leukemia (AGL) treated with either cytosine arabinoside-cytoxan (CA-CYT) or Mini-COAP (CA-CYT with vincristine sulfate [VCR] and prednisone) have been in continuous complete remission 4 years or more. CA and CYT were each given in the dosage of 120 mg/m2 intravenously, daily in 3 divided doses, for 4 days. Induction consisted of two courses given at intervals of 2 weeks; during maintenance the courses were repeated at intervals of 4 weeks. In the Mini-COAP regimen, standard 28-day VCR-prednisone therapy was superimposed on CA-CYT induction and 4-day VCR-prednisone pulses were superimposed on CA-CYT maintenance. Transient moderate to severe myelosuppression was frequent; other manifestations of toxicity were mild. Administration of drugs at home was feasible in many instances. Mini-COAP was proved to be an effective therapeutic regimen for young children with AGL and should be considered as initial therapy.

Extrarenal Wilms tumor.

The previous reports of extrarenal Wilms tumor are reviewed and two additional patients presented. The clinical and pathologic features are discussed. The diagnosis of extrarenal Wilms tumor does not imply a bad prognosis. Treatment should utilize multidrug chemotherapy similar to the guidelines set by the National Wilms Tumor Study.