Lila Penchansky

IS URINE CULTURE NECESSARY TO RULE OUT URINARY TRACT INFECTION IN YOUNG FEBRILE CHILDREN

OBJECTIVE To determine whether the absence of pyuria on the enhanced urinalysis can be used to eliminate the diagnosis of urinary tract infection, avoiding the need for urine culture and sparing large health care expenditures. DESIGN Results of an enhanced urinalysis (hemocytometer counts and interpretation of Gram-stained smears) performed on uncentrifuged urine specimens obtained by catheter were correlated with urine cultures in young febrile children at the Childrens Hospital of Pittsburgh Emergency Department. In a group of 4253 children (95% febrile) less than 2 years of age, pyuria was defined as > or = 10 white blood cells/mm3, bacteriuria as any bacteria on any of 10 oil immersion fields in a Gram-stained smear and a positive culture as > or = 50,000 colony-forming units/ml. A subgroup of 153 children with their first diagnosed urinary tract infection were enrolled in a separate treatment trial, acute phase reactants (peripheral white blood cell count, erythrocyte sedimentation rate and C-reactive protein) were obtained and 99Tc-dimercaptosuccinic acid renal scans were performed. RESULTS The presence of either pyuria or bacteriuria and the presence of both pyuria and bacteriuria have the highest sensitivity (95%) and positive predictive value (85%), respectively, for identifying positive urine cultures. Because a white blood cell count in a hemocytometer is the technically simpler component of the enhanced urinalysis, we chose to analyze the false negative results and achievable cost savings of using pyuria alone as the sole criterion for omitting urine cultures. If in this study urine cultures had been performed only on specimens from children who had pyuria or were managed presumptively with antibiotics, cultures of 2600 (61%) specimens would have been avoided. Twenty-two of 212 patients with positive urine cultures would not have been identified initially. However, based on interpretation of acute phase reactants, initial 99Tc-dimercaptosuccinic acid scan results, response to management and incidence of renal scarring 6 months later, 14 of the 22 patients most likely had asymptomatic bacteriuria and fever from another cause. The remaining 8 patients probably had early urinary tract infection. CONCLUSIONS The analysis of urine samples obtained by catheter for the presence of significant pyuria (> or = 10 white blood cells/mm3) can be used to guide decisions regarding the need for urine culture in young febrile children.

Acute leukemia following a malignant teratoma in a child with Klinefelter's syndrome: case report and review of secondary leukemias in children following treatment of a primary neoplasm.

A case of Klinefelters syndrome with the development of a mediastinal teratocarcinoma is reported suggesting that the association of a gonadotropin‐secreting tumor with the XXY chromosomal abnormality may be more than coincidental. Whereas this child appeared to survive the effects of the teratocarcinoma, he succumbed to acute leukemia two years later. This prompted a review of secondary leukemias in children following chemotherapy/radiotherapy for another primary malignancy. These patients responded poorly to treatment of the secondary leukemia with a median survival of about four months. The incidence of secondary leukemias might be expected to be on the rise as increasing numbers of pediatric cancer patients are surviving longer after treatment with agents that are potentially leukemogenic or carcinogenic themselves. Children who have survived cancer and its therapy present special problems and it will be necessary for the pediatrician and practitioner to monitor these children.

Transient 7q- in association with megaloblastic anemia due to dietary folate and vitamin B12 deficiency.

Purpose: We describe a ease of acquired megaloblastic anemia in a 71/2-year-old while boy whose bone marrow showed unusual morphology and a nonrandom del(7q). Methods and Results: This patient was found to have megaloblastic anemia due to acquired folic acid and vitamin B12 deficiencies. Bone marrow examination exhibited unusual morphology, including intranuclear inclusions. Cytogenetic analysis revealed a nonrandom del(7q). a clonal abnormality usually associated with the myelodysplastic syndrome (MDS) or secondary acute myelogenous leukemia (AML). Specific treatment with both folic acid and vitamin B12 corrected the clinical as well as the marrow morphologic and cytogenetic abnormalities. Conclusions: Megaloblastic anemia causes abnormalities in DNA synthesis and repair that may result in unusual marrow findings, both morphologic and cytogenetic. Such findings must be interpreted with caution in view of total reversibility with specific vitamin therapy.

Detection of neuroblastoma in the bone marrow: biopsy versus aspiration.

Purpose: Multiple studies have emphasized the higher yield of detection of metastatic neuroblastoma (MNb) by bone marrow biopsy (BMB) than by bone marrow aspiration (BMA). Because the need for BMA has been questioned, the yield of both procedures was investigated at diagnosis and during the course of disease. Methods: For morphologic and immunohistochemical detection of MNb, 289 specimens obtained by BMA and BMB from 57 children with neuroblastoma were reviewed. Results: In 34% of cases, MNb was present in both the aspirate and biopsy specimen. MNb was present in only the biopsy specimen in 8% and in only the aspirate in 6%. In 52%, neither BMA nor BMB detected MNb. In 15 of 18 cases in which MNb was present in the aspirate only, protein gene product 9.5 (PGP) stain was performed on the biopsy specimen. In one case, this helped to identify MNb that was not evident by routine hematoxylin and eosin stain. Of the 24 cases in which only the BMB was positive, 3 were identified only by means of PGP stain. Conclusions: Even with the additional use of immunohisto-chemistry, both BMA and BMB should be performed to have the highest yield of detection of MNb in bone marrow.

An abnormal clone with monosomy 7 and trisomy 21 in the bone marrow of a child with congenital agranulocytosis (Kostmann disease) treated with granulocyte colony-stimulating factor : evolution towards myelodysplastic syndrome and acute basophilic leukemia

Cytogenetic analysis of bone marrow cells revealed an abnormal clone with monosomy 7 and trisomy 21 in a 12-year-old child with Kostmann disease (KD). The patient presented with anemia, thrombocytopenia, and splenomegaly after 5 years of treatment with granulocyte colony-stimulating factor (G-CSF). The bone marrow morphology was consistent with the diagnosis of myelodysplastic syndrome (MDS). Administration of G-CSF was discontinued at this point. Bone marrow studies 2 and 5 months later showed persistence of both myelodysplasia and the abnormal clone with monosomy 7 and trisomy 21. Monosomy 7 was also confirmed by fluorescence in situ hybridization (FISH). After 2 months of follow-up, the patient presented with acute basophilic leukemia, a very rare variant of acute myeloid leukemia (AML), expressing the same bone marrow chromosome abnormalities as observed earlier. This is a rare case of KD with prolonged survival and a cytogenetically abnormal clone evolving to MDS and acute basophilic leukemia. The significance of monosomy 7 and trisomy 21 in KD treated with G-CSF is discussed.

Idiopathic Hypereosinophilic Syndrome Terminating in Acute Lymphoblastic Leukemia

Idiopathic hypereosinophilic syndrome (IHES) is a heterogeneous group of disorders characterized by multisystem dysfunction and persistent, extreme eosinophilia of unknown cause. We describe a 9-1/2-year-old boy whose course included several unusual clinical features and terminated 2 years after diagnosis in acute lymphoblastic leukemia (ALL). Serial studies suggest that leukemia was not present earlier in his course. We speculate that this child may have had an evolving lymphoproliferative syndrome with a terminal blast crisis to which the eosinophilia was a nonmalignant leukemoid reaction.

Non‐Hodgkin's lymphoma in children. An analysis of 122 cases from Argentina

One hundred twenty two children with non‐Hodgkins lymphoma were studied from January 1966 to December 1975. The first group (1966–1972) did not receive an uniform treatment. The second group (1973–1975) entered in a G.A.T.L.A. protocol consisting of: vincristine‐prednisone plus surgery and/or radiotherapy as induction treatment, craniocervical radiotherapy and intrathecal methotrexate as CNS preventive treatment and anti‐leukemia (6‐mercaptopurine, methotrexate and vincristine‐prednisone pulses) or anti‐lymphoma (COPP) treatment as maintenance, in a randomized trial. Comparison of survival of the two groups are as follows: series 1966–1972, 22% and 20% at 12 and 24 months of evolution, respectively, and series 1973–1975, 33% and 26% at 12 and 24 months, respectively. After 2 years of complete remission we have not seen any relapse. We conclude that 1) this disease is highly malignant and must be treated with more intensive chemotherapeutic treatment, and 2) there is no difference between antileukemia or anti‐lymphoma maintenance treatment, as yet.

Normal Bone Marrow

The remarkably constant preservation of numerical levels of blood cells in normal individuals is the result of a balance between cell formation and destruction. The production of blood cells, hematopoiesis, is the main function of the human bone marrow (BM), which originates during intrauterine life at a crownrump length of 95 mm (Chen and Weiss 1975).

Pancytopenia and vacuolation of marrow precursors associated with necrotizing encephalopathy

Subacute necrotizing encephalopathy (SNE) or Leigh disease is an autosomal recessive disorder associated with various defects of oxidative phosphorylation. Two reports have described the concurrence of SNE with pancytopenia and vacuolation of bone marrow precursors, and have raised the possibility that this symptom complex may be part of a spectrum of diseases which includes Pearsons syndrome (vacuolation of bone marrow precursors, sideroblastic anaemia, exocrine pancreatic dysfunction). We describe a case of Pearsons syndrome in which haematological manifestations antedated progressive neurological deterioration by several years. Cytogenetic studies showed an inverted duplication of chromosome 9 (qh) [inv dup (9) (qh)]. We suggest that cytopenia associated with vacuolation of bone marrow precursors even without clinically apparent central nervous system pathology should prompt consideration of SNE, or related diseases. Conversely, a diagnosis of SNE should prompt evaluation of other organ system functions including bone marrow. Cytogenetic evaluation of other patients with SNE may determine whether the 9 (qh) findings are pathogenetic.

A new procedure for cell lineage determination in acute leukemias. Myeloperoxidase mRNA detection.

Determination of cell lineage in acute leukemias is essential for diagnosis and treatment. Detection of myeloperoxidase (MPO) mRNA establishes myeloid lineage of leukemic blasts that may be too primitive to be identified as myeloblasts based on morphology, cytochemistry, or im-munophenotype. A highly specific and sensitive new procedure for MPO mRNA detection has been developed using HL-60 cells. It involves a microprocedure for total cellular RNA extraction, reverse transcription, and specific amplification of target sequences in the resulting MPO cDNA. by the polymerase chain reaction. Specific primers are designed to amplify an 89-base pair (bp) sequence from the signal peptide, 179 and 318-bp sequences from the start and end, respectively, of the heavy-chain sequence, and a 255-bp sequence overlapping the prore-gion and light chain. The correct-size amplification products. detected electrophoretically, demonstrate MPO mRNA expression in the leukemic cells analyzed. The sensitivity of this new procedure was evaluated on serial concentrations of HL-60 cells and was found to be 10–104 cells depending on the MPO cDNA amplified sequence. No amplification products were obtained using peripheral blood lymphocytes as a negative cellular control. The specificity of the procedure is demonstrated by Southern blotting and hybridization with 32P-labeled oligonucleotide probes specific for each of the amplified sequences. An additional advantage of this procedure is availability of results in 8–24 h, compared with 1–2 weeks for conventional RNA methods.