Search PubMed⌕ Search

Biomedical subjects

L Penchansky

Publications and source records attributed to L Penchansky.

At least 19 recordsLinked to original sources
PubMed1999

Chylous pleural effusions simulating leukemic infiltrate associated with thoracoabdominal disease and surgery in infants.

Surgical procedures and diseases in childhood involving damage to or obstruction of the thoracic duct and related lymphatic channels can cause pleural effusions that are often chylous and can be massive. The morphology of fluid cytology in these cases can prompt a mistaken diagnosis of a hematolymphoid malignancy. We describe 6 infants, aged 3 days to 5 months, in whom thoracoabdominal disease and/or surgical procedures interfered with lymphatic drainage of the thorax and pleural space. In 5 cases, the clinically significant chylous pleural effusion was postoperative; in 1 case, it was related to congenital abnormalities. After chest tube drainage, the effusion resolved in all cases. Fluid cytology revealed a predominant population of small to medium immature-appearing cells with moderate amounts of basophilic cytoplasm without granules. The nuclei were often irregular or slightly lobulated, with evenly dispersed chromatin and occasionally prominent nucleoli. Flow cytometry performed on these cases revealed a heterogeneous population of lymphoid cells, most of which showed phenotypic markers typical for mature T cells. A complete patient history and ancillary studies in such cases can correctly characterize the cells to reach an accurate diagnosis.

Abnormalities, Multiple↗
PubMed1997

Transient erythroblastopenia of childhood associated with human herpesvirus type 6, variant B.

Transient erythroblastopenia of childhood (TEC) is a disorder of young children ages 3 months to 4 years that is characterized by anemia associated with reticulOcytopenia and decreased red blood cell precursors in the bone marrow aspirate (BMA). A viral cause has been suspected for TEC. Bone marrow aspirate-derived DNA from 14 children with anemia or another hematologic disorder, including two children with TEC, were analyzed by polymerase chain reaction for human herpesvirus type 6 (HHV-6) DNA and human parvovirus B19 DNA. Testing revealed an HHV-6 variant B DNA in both children with TEC but not in the children who did not have TEC. The BMAs from these two children contained large pronormoblasts and an extensive lymphoid infiltrate. We proposed that HHV-6 may be a causative agent of TEC in immunocompetent children. This hypothesis is based on the demonstrated ability of HHV-6 to suppress the formation of burst-forming units-erythroid (BFU-E) and granulocyte macrophage-colony-forming units (GM-CFU) in vitro, and in vivo in HHV-6-infected patients who undergo bone marrow transplantation.

Adolescent↗
PubMed1996

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 Children's 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.

Bacteriological Techniques↗
PubMed1996

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

PURPOSE: We describe a case of acquired megaloblastic anemia in a 7 1/2 year-old white 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.

Anemia, Megaloblastic↗
PubMed1995

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.

Agranulocytosis↗
PubMed1994

Acute myeloblastic leukemia with a pericentric inversion of chromosome 6 in a child with Down syndrome.

Cytogenetic analysis of bone marrow cells demonstrated a pericentric inversion of chromosome 6 when acute myeloblastic leukemia (AML) was diagnosed in a 15-month-old child with Down syndrome. The abnormal clone with inv(6)(p24q16) was associated with FAB-M1 AML and disappeared when a complete remission was achieved. This is a unique cytogenetic abnormality for FAB-M1 AML in a child with Down syndrome and, to our knowledge, is only the second case of a pericentric inversion of chromosome 6 reported in AML.

Chromosome Inversion↗
PubMed1994

Pyuria and bacteriuria in urine specimens obtained by catheter from young children with fever.

Results of urinalysis and culture of 2181 urine specimens obtained by catheter from febrile children aged less than 24 months were analyzed to determine the following: (1) an optimal cutoff point in considering a bacterial colony count clinically "significant," (2) the accuracy of leukocyte esterase and nitrite tests in identification of pyuria and bacteriuria, and (3) the utility of pyuria (defined as > or = 10 leukocytes/mm3) in the discrimination of urinary tract infection from asymptomatic bacteriuria. Among 110 urine cultures with > or = 10,000 colony-forming units per milliliter, 92 (84%) had > or = 100,000 CFU/ml, 10 (9%) had 50,000 to 99,000 CFU/CFU/ml and 8 (7%) had 10,000 to 49,000 CFU/ml. Urine specimens with 1000 to 49,000 CFU/ml were more likely than specimens with > or = 50,000 CFU/ml to yield Gram-positive or mixed organisms (36/60 vs 7/109; p < 0.001). A count of < 10 leukocytes/mm3 was almost invariably associated with a sterile culture; a count of > or = 10 leukocytes/mm3 was found in 93 of 102 patients with > or = 50,000 CFU/ml. The dipstick leukocyte esterase test had sensitivities of 52.9% and 66.7% in detecting > or = 10 leukocytes/mm3 and > or = 20 leukocytes/mm3, respectively. The dipstick nitrite test had a sensitivity of 31.4% in detecting bacteriuria (> or = 50,000 CFU/ml). Acute pyelonephritis was diagnosed by a renal scan with dimercaptosuccinic acid labeled with technetium 99m in 50 (77%) of 65 patients with > or = 10 leukocytes/mm3 but in none of five patients with < 10 leukocytes/mm3 (p < 0.01). The findings in these five patients were consistent with colonization of the urinary tract rather than infection. For urine specimens obtained by catheter, we believe that urinary tract infection is best defined by both a leukocyte count > or 10/mm3 and a CFU count > or = 50,000/ml. This definition almost always discriminates among true urinary tract infection, bacteriuria resulting from contamination of the urine specimen, and asymptomatic bacteriuria.

Bacteriuria↗
PubMed1994

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 Pearson's syndrome (vacuolation of bone marrow precursors, sideroblastic anaemia, exocrine pancreatic dysfunction). We describe a case of Pearson's 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.

Bone Marrow↗
PubMed1994

A non-classical translocation involving 17q12 (retinoic acid receptor alpha) in acute promyelocytic leukemia (APML) with atypical features.

Acute promyelocytic leukemia (APML) almost always involves a chromosomal translocation t(15:17) that results in the fusion of the retinoic acid receptor alpha (RAR alpha) gene with a transcription factor gene called PML. Several cases of APML with t(11;17) have recently been described, involving fusion of the RAR alpha gene with a new zinc finger gene named PLZF. We report here a second non-classical translocation, t(5;17), with a rearranged RAR alpha gene in a child with APML. Based on restriction endonuclease analysis, the rearrangement of RAR alpha occurred within the second intron, the common breakpoint site for t(15;17). The leukemic cells in the bone marrow aspirate were a mixture of hypergranular and hypogranular bilobed promyelocytes. Although less than 1% abnormal promyelocytes were identified after induction therapy, cytogenetics revealed persistent t(5;17). Therefore, the child was treated with all-trans-retinoic acid (ATRA). There was no disease progression, and one marrow was interpreted as remission, with confirmation by cytogenetics which failed to reveal the translocation. However, disease reoccurred shortly after completion of ATRA. This poor response to ATRA may be an additional characteristic associated with non-classical translocations in APML. The identification of a second variant translocation involving the RAR alpha gene in APML suggests yet another RAR alpha rearrangement related to neoplastic myelopoiesis.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Spontaneous remission of infantile acute nonlymphocytic leukemia for 11 years in a child with normal karyotype.

BACKGROUND: Leukemia or a leukemia-like picture in phenotypically normal infants with a normal marrow karyotype who undergo spontaneous remission is extremely unusual. RESULTS: A 6-week-old, phenotypically normal boy first was seen in 1979 with hepatosplenomegaly, a 36 x 10(9)/l leukocyte count, a leukoerythroblastic picture, and increased blasts in the bone marrow aspirate. Because no other known causes of leukemoid reaction could be demonstrated, the picture was consistent at that time with acute nonlymphocytic leukemia (ANLL), French-American-British (FAB) M1; however, because of the age of the child, the low blast count, normal cytogenetics, and questions about this diagnosis, treatment was withheld. Hematologic laboratory values normalized by the time he was 1 year of age. Eleven years later, he presented a similar picture that rapidly progressed to overt leukemia (FAB M1). A normal marrow karyotype was consistent throughout the 11 years of follow-up. Treatment of ANLL was initiated, resulting in marrow remission. This was followed by allogeneic bone marrow transplantation. He had a relapse again and was retreated, achieving a second marrow remission, and had a second allogeneic bone marrow transplantation. However, the patient died of venoocclusive disease of the liver after the second transplant. CONCLUSION: The diagnosis and prognosis of infants with an abnormal hematologic picture similar to ANLL but who are phenotypically and karyotypically normal are not as straightforward as in the older child or adult. Treatment should be withheld in this setting until the leukemic process is overt.

Child↗
PubMed1993

Flow cytometric study of the expression of neutral endopeptidase (CD10/CALLA) on the surface of newborn granulocytes.

The susceptibility of newborn infants to bacterial infections is well documented. Neutrophils play an important role in defense against bacterial infection, the most common kind of infection in the newborn period. Many studies of lymphocyte surface characteristics during that period of life are available, but there are no reports on the surface immunophenotype of the granulocytes at birth. Because some of their membrane associated antigens have been identified as enzymes (CALLA/CD10), neutral endopeptidase, and (CD13) amino peptidase that could play a role in the biological functions of neutrophils, a study of the membrane phenotype appeared potentially important. Using flow cytometry, we studied the expression of a panel of the antigens expressed on mature neutrophils including CD10, CD13, and CD33 in 28 full-term babies and 19 adults. A significantly (p < 0.001) lower expression of CD10, CD13, and CD33 was found in full-term babies compared with 19 adults. These data raise two points: first, that because CD10 is detected only on segmented granulocytes, the low level of CD10 observed in neonates is consistent with a degree of immaturity of the neutrophil membrane, and second, that the deficiency of endopeptidase may impair neutrophil interactions with peptide effectors and thus play a role in the increased susceptibility to bacterial infections exhibited in newborns.

Adult↗
PubMed1993

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 immunophenotype. 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 proregion 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 10-10(4) 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.

Base Sequence↗
PubMed1992

Effect of low neutral endopeptidase expression on response to fMLP.

The effects of the low neutral endopeptidase (24.11/CD10) exhibited by cord blood neutrophils on response to the peptide mediator of cell function f-met-leu-phe (fMLP) were investigated. Oxidative radical release (superoxide and hydrogen peroxide) and chemotactic responses to fMLP were determined and compared to the responses of normal adult neutrophils. The effect of fMLP on CD10 expression as measured by flow cytometry also was evaluated. The data show that cord blood neutrophils produce increased amounts of O2- and H2O2 largely because of a prolonged reaction time to fMLP. In addition, adult polymorphonuclear neutrophil leukocytes increase the intensity of their expression of CD10 following fMLP stimulation, whereas cord blood CD10 expression does not change. Evaluation of chemotaxis demonstrated that cord blood neutrophils exhibited a shift in the fMLP dose-response relationship showing relatively better chemotaxis to lower concentrations. In support of this observation, the inhibition of endopeptidase on adult polymorphonuclear neutrophils leukocytes by phosphoramidon was associated with an augmentation of chemotaxis to 10(-9) and 10(-10) mol/L fMLP. These studies demonstrate that cord blood and adult neutrophils respond differently to fMLP and suggest that membrane endopeptidase plays a role in the observed response patterns. The low level of expression of CD10 on cord blood neutrophils and the failure to increase its expression after fMLP stimulation suggests that adult neutrophils have preformed intracellular CD10 that is not present in the newborn. We propose that the lack of endopeptidase on cord blood neutrophils together with other known features of immaturity may play a role in the overall compromised host defense exhibited by the newborn.

Adult↗
PubMed1992

Morphological diagnosis of parvovirus B19 infection. A cytopathic effect easily recognized in air-dried, formalin-fixed bone marrow smears stained with hematoxylin-eosin or Wright-Giemsa.

Readily identifiable intranuclear inclusions characterize parvovirus B19 cytopathic effect in formalin-fixed, paraffin-embedded material. Such inclusions are not apparent in air-dried smears of bone marrow aspirates. Brief formalin fixation of bone marrow smears, followed by either hematoxylin-eosin or Wright-Giemsa staining, permitted easy detection of parvovirus B19 inclusions in material from a renal transplant recipient with parvovirus B19 infection documented serologically and by electron microscopy. Formalin fixation of bone marrow and peripheral blood smears before hematoxylin-eosin or Wright-Giemsa staining may simplify the morphological diagnosis of parvovirus B19 infection.

Bone Marrow Diseases↗