Karyotype Anomalies in Patients with Disorders of Sexual Development.

OBJECTIVES: Objectives Disorders of sex development(DSD)can result in discordance between the chromosomal and anatomicand/orphenotypic sex of a patient. Reporting patients with uncommon karyotypes associated with DSD is important for clinical comparison of developmental outcomes, and management. Methods We describe three female patients with karyotypes resulting in DSD and the use of a combination of chromosomes and FISH techniques to identify potential causes. Results The first patient was mosaic for idic(Y) that was negative for SRY by FISH. The second patient had idic(Y) that was positive for SRY by FISH. The third patient had an unbalanced translocation between the X chromosome and chromosome 2 [der(2)(X;2)] and XY. These three patients illustrate three different genetic mechanisms underlying DSD. Conclusion Our findings expand the list of abnormal karyotypes that can be associated with DSD and highlight the importance of SRY and DAX1 in phenotypic and functional sexual development.

Cytogenetic and Cytogenomic Microarray Characterization of Chromothripsis in Chromosome 8 Affecting MOZ/NCOA2 (TIF2), FGFR1, RUNX1T1, and RUNX1 in a Pediatric Acute Myeloid Leukemia.

Concurrent perturbations in different driver genes have been reported primarily in lymphoma. In acute myeloid leukemia (AML), cases with concurrent alterations in 2 driver genes are infrequently reported. In contrast to pathogenetic pathways in lymphoma with concurrently perturbed genes, the initial gene alteration in AML arrests maturation and the alteration in the second gene promote self-renewal of the blasts. Here, we report a unique case of infantile leukemia in which chromothripsis in chromosome 8 completely altered the G-band structure and resulted in concurrent changes in MOZ/NCOA2, FGFR1, RUNX1T1, and RUNX1. These multiple-hit abnormalities in AML have not been reported previously.

A Chronic Myelogenous Leukemia (CML) Case with a Cryptic Insertion of the ABL1 Gene of Chromosome 9 into 22 Resulting in a Fusion Signal on the Derivative 22: 46,XY.ish ins(22;9)(q11.2;q34q34)BCR+,ABL1.

Chronic myelogenous leukemia (CML) is characterized by the specific cytogenetic translocation t(9;22)(q34;q11.2), also called the Philadelphia (Ph) chromosome. We present a case of a cryptic BCR/ABL1 fusion, which was not originally detected by standard karyotyping. The patient is a forty-seven-year-old man who presented with leukocytosis. Bone marrow biopsy was consistent with CML in chronic phase with no increase in myeloblasts. Conventional cytogenetic studies revealed a 46,XY karyotype. Despite this finding, the patient was started on hydroxyurea therapy followed by Gleevec. At six-month follow-up, a repeat karyotype was again normal, though FISH analysis was positive for BCR/ABL1 fusion. FISH performed on previously G-banded metaphases showed a very rare cryptic insertion involving 22q11. While most genetic abnormalities in CML can be diagnosed using classical cytogenetics, molecular studies remain the gold standard in definitively identifying the characteristic BCR/ALB1 fusion. This case represents one of the variant cryptic rearrangements in CML where clinical correlation with morphologic, immunophenotypic, cytogenetics and FISH findings are indicated and highlights the importance of molecular testing at the time of primary diagnosis.

Recombinant chromosome 7 in a mosaic 45,X/47,XXX patient.

Individuals with pericentric inversions are at risk for producing offspring with chromosomal gains and losses, while those carrying paracentric inversions usually produce unviable gametes [Madan, 1995]. In this current study, we present a newborn with dysmorphic features and malformations, whose karyotype showed an abnormal copy of chromomosome 7 described at first as add(7)(q32) as well as mos 45,X/47,XXX. Array comparative genomic hybridization (CGH) revealed an interstitial deletion in the long arm of chromosome 7 involving bands q35 to q36.3 but retaining the 7q subtelomere. The patient's deletion is believed to be due to meiotic recombination in the inversion loop in the phenotypically normal father who seems to carry two paracentric inversions in the long arm of chromosome 7, which was described as rec(7)(7pter- > q35::q36.3- > 7qter)pat. The abnormal copy of chromosome 7 in the father has been described as: der(7)(7pter- > q22.1::q36.3- > q35::q22.1- > q35::q36.3- > 7qter). This is a unique karyotype that to our knowledge has not been previously reported in the literature and predisposes to meiotic recombination that can result in deletions or duplications of 7q35-36.

Clinico-microbiological study of opportunistic infection in HIV seropositive patients.

OBJECTIVES: The present study was undertaken to determine the prevalence of respiratory, gastrointestinal and other pathogens in 100 Human Immunodeficiency Virus (HIV) seropositive patients. SETTINGS: This study was carried out on randomly selected 100 HIV seropositive patients from S. S. G. Hospital during the period from Jan 2006 to Jan 2007. MATERIALS AND METHODS: Sputum samples, stool samples and oral swabs were collected from all the patients and cerebrospinal fluid (CSF) was collected from symptomatic patients and processed as per the standard protocol. Sputum samples were examined by microscopy and cultured for bacterial respiratory pathogens. Stool samples were concentrated and examined by microscopy for enteric parasites. Oral swabs and CSF were also examined microscopically and cultured for fungal pathogens. CSF was also examined for bacterial pathogens. RESULTS: A total of 101 pathogens were detected in 60 patients. More than one pathogen was observed in 30 patients. Candida was the commonest isolate (32.67%), followed by Mycobacterium tuberculosis (22.71%) and Cryptosporidium parvum (19.8%). CONCLUSIONS: Since opportunistic infections are a major cause of mortality and morbidity in HIV seropositive patients, an early diagnosis and effective treatment are required to tackle them. The type of pathogens infecting HIV patients varies from region to region, and therefore such patients should be constantly screened for these pathogens.

Acute myeloid leukemia with inv(16) with CBFB-MYH11, 3'CBFB deletion, variant t(9;22) with BCR-ABL1, and del(7)(q22q32) in a pediatric patient: case report and literature review.

Coexistence of inv(16) and t(9;22) is a rare chromosomal aberration, one that has been described in chronic myelogenous leukemia (CML), mainly in myeloid blast crisis, and de novo acute myeloid leukemia (AML). Approximately 14 cases have been reported, including only 1 pediatric case. Here we present the case of a 13-year-old boy with a new diagnosis of AML with some features of monocytic differentiation. Conventional cytogenetic analyses on unstimulated blood showed three related abnormal clones with inv(16) in the stemline: 46,XY,inv(16)(p13.1q22)[2]/46,idem,del(7)(q22q32)[16]/46,idem,t(9;22;19)(q34;q11.2;p13.1)[2]. Fluorescence in situ hybridization (FISH) studies on interphase nuclei and previously G-banded metaphases showed a 3'CBFB deletion and confirmed the presence of the Philadelphia chromosome in a t(9;22;19) rearrangement. Deletion 7q31 was also confirmed by interphase FISH analysis. The patient was treated with standard AML chemotherapy plus gemtuzumab as part of a clinical trial. At 10-months follow-up, he was in remission. To the best of our knowledge, this is the first description of a pediatric case of de novo AML with a stemline showing inv(16) along with 3'CBFB deletion, an abnormal clone revealing in addition a del(7)(q22q32), and another clone with a t(9;22;19)(q34;q11.2;p13.1) as an additional abnormality.

A Cryptic t(1;21;8)(p36;q22;q22) in a Case of Acute Myeloid Leukemia with Maturation.

The t(8;21)/RUNX1-RUNX1T1 is found in ~5 percent of cases of acute myeloid leukemia (AML) and in 10 percent of the prior AML with maturation (M2) category of the French-American-British (FAB) classification. While AML with t(8;21) is considered a distinct entity with a favorable prognosis, the clinical consequence of variant translocations is less well defined. In this report we described a 45 year-old male patient having a diagnosis of AML-M2 with morphologic and immunophenotypic features suggestive of t(8;21). However, the initial karyotypic analysis revealed an apparently balanced translocation between 1p36 and 8q22. Further fluorescence in situ hybridization (FISH) studies using the AML1/ETO and the p58 probes from Abbott Molecular, demonstrated a three-way translocation between chromosomes 1, 21, and 8, with single fusion of RUNX1-RUNX1T1 on the derivative chromosome 8 [t(1;21;8)(p36.1;q22;q22)]. The patient was in complete remission after induction therapy followed by consolidation. This report demonstrates the importance of FISH studies for detection of cryptic specific chromosome rearrangements that may have prognostic significance.

Un caso de leucemia mieloide aguda en un paciente con una translocación (1; 21; 8)y una sola fusión AML1-ETO / A case of water myeloid leukemia in a patient with a translocation (1, 21, 8) and one AML1-ETO fusion

The t(8;21) accounts for 5-12% of AML patients, often occurring in the younger population (1). This translocation fuses the AML 1 gene on chromosome 21q22 and the ETO gene on 8q22 resulting in a AML1-ETO hybrid transcript. Under the World Health Organization (WHO) classification, the t(8;21) is distinctly characterized under AML with recurrent aberrations with a favorable prognosis. Variant t(8;21; var) display comparable clinical manifestations compared to the classical translocation; however, they are less defined and their clinicak significance remains arguable. Complex t(8;21) variants account fo approximately 3-4% of all AML1-ETO fusion transcripts with approximately 100 variants described in the literature (1,2). In this article, we discuss a variant (8;21) translocation in AML. Chromosomal analysis of this case using conventional cytogenetics showed an apparently balanced transcolation between the short arm of chromosome 1 at 1p36 and the long arm of chromosome 8 at 8q22. Subsequent FISH studies demonstrated that there was also a fusion of the AML1 and ETO genes on the derivative chromosome 8, a key event in M2, a small ETO signal on chromosome 1, a normal ETO signal on the other homologue 8 and two AML1 signals (a small AML1 signal on the normal copy of chromosome 21). This report demonstrates how important is to do FISH studies to characterize a specific rearrangement in the management of hematological maligancies.

La translocación (8;21) se presenta en un 5-12% de casos de leucemia mieloide aguda y ocurre preponderamente en una población joven de estos pacientes. En esta translocación se fusionan los genes AML1 en el cromosoma 21q22 con el gen ETO en el cromosoma 8 en el locus 8q22 produciendo un gen híbrido AML1-ETO, el cual esta asociado a un pronóstico bastante favorable. En este artículo presentamos un paciente cuyo cariotipo, usando citogenética convencional, mostró una "translocación aparentemente balanceada" entre el brazo corto del cromosoma 1 en la banda 1p36 y el brazo largo del cromosoma 8 en la banda 8q22. Los estudios de FISH usando la sonda de dos colores y doble fusión AML1/ETO determinaron que se trataba de una translocación triple entre los cromosomas 1, 8 y 21 ya que se pudo observar una fusión AML1/ETO el cromosoma 8 derivado, el cual es el evento clave en la translocación típica (8;21). Se observó además una señal de AML1 pequeña en el cromosoma derivado 21, una copia normal completa de AML1 en el homólogo normal 21, una señal pequeña de ETO en el brazo corto del cromosoma 1 así como una copia normal de ETO en el homólogo normal 8. El presente estudio nos permite ver la importancia de FISH en la caracterización de anormalidades cromosómicas así como el monitoreo de enfermedades hematológicas.

Should electroconvulsive therapy be an early consideration for suicidal patients?

INTRODUCTION: This article describes a quality management project undertaken for the purpose of ensuring that the most appropriate patients were being selected for electroconvulsive therapy (ECT) at an 80-bed, state-operated, civil psychiatric facility for the seriously mentally ill. METHOD: Thirty mentally ill patients, including patients with comorbid substance abuse diagnoses, were treated with ECT. Pre-ECT and post-ECT scores on the 24-item Brief Psychiatric Rating Scale (BPRS-24) were compared with admission and discharge BPRS-24 scores of a control group treated with psychotropic medication. RESULTS: ECT-treated patients demonstrated greater improvement in BPRS scores during a shorter period than did non-ECT-treated patients. Furthermore, the greatest improvement was seen in the areas of depression and expressed suicidal intent. An unanticipated result was that patients with comorbid substance abuse diagnoses treated with ECT showed the most improvement in these areas. CONCLUSION: ECT was shown to be particularly useful in the treatment of suicidally inclined depressed patients, suggesting that ECT should be an early consideration for suicidal patients.

Mutational study of the bacterial hemoglobin distal heme pocket.

Ligand binding experiments on three mutants in the distal heme pocket of Vitreoscilla hemoglobin (GlnE7His, ProE8Ala, and GlnE7His,ProE8Ala) were used to probe the role of GlnE7 and ProE8 in the pocket's unusual structure. The oxygen dissociation constants for the wild type, E8Ala mutant, and E7His mutant proteins were 4.5, 4.7, and 1.7microM, respectively; the K(d) for the double mutant was not determinable by our technique. Visible-Soret spectra of the carbonyl and cyanyl forms and FT-IR of the carbonyl form of the E8 mutant were similar to those of the wild type; the opposite was true for the GlnE7His and GlnE7His,ProE8Ala mutants, which also differed from wild type in the visible-Soret spectra of their oxidized forms. Models of the effects of the mutations on distal pocket structure were consistent with the experimental findings, particularly the larger effects of the GlnE7His change.

Effect of different strains of Saccharomyces cerevisiae on production of volatiles in Napa Gamay wine and Petite Sirah wine.

Napa Gamay grapes were fermented with four different strains of the yeast Saccharomyces cerevisiae (VL1, MI16, Fermirouge, and RA17). Petite Sirah grapes were fermented with seven different strains of the same yeast (BM45, Fermirouge, RA17, NI, CX3079, A350, and A796). Volatile compounds formed in the wines were analyzed by gas chromatography/mass spectrometry. Volatile compounds found in both wines were alcohols, esters, and acids, as well as some miscellaneous compounds. Isoamyl alcohol was the compound found in the highest relative amount with all four yeast strains in the Napa Gamay wines, followed by 2-phenyl ethanol, monoethyl succinate, and hexanoic acid. The relative amounts of isoamyl alcohol ranged from 30.84% (VL1) to 43.28% (RA17). Major volatile compounds found in Petite Sirah wines were isoamyl alcohol, 2-phenyl ethanol, 2-hydroxy ethyl propanoate, monoethyl succinate, and octanoic acid. The several esters, including 2-hydroxyethyl propanoate, may contribute to the fruity flavor of Petite Sirah wines. Overall, the S. cerevisiae yeast strains used to ferment Napa Gamay grapes and Petite Sirah grapes produced the same major components, with certain variations in formation levels.