Characterization of the p67phox gene: genomic organization and restriction fragment length polymorphism analysis for prenatal diagnosis in chronic granulomatous disease

The genetic defect in the p67phox-deficient form of chronic granulomatous disease (CGD) follows an autosomal recessive pattern of inheritance. When genomic DNA from normal individuals is digested with HindIII and probed with p67phox cDNA an allelic restriction fragment length polymorphism (RFLP) of 4.0 kb or 2.3 kb is detected. We cloned and characterized the p67phox gene using the cDNA and sequenced the exon/intron boundaries, mapping 16 exons on the 40-kb gene. The polymorphic region was then sequenced to identify the inheritance pattern of amniocentesis-derived fetal cells by genomic amplification. The proband, a 9-year-old female patient with p67phox-deficient CGD, and her phenotypically normal mother are homozygous for the RFLP marker, whereas the father and two brothers are heterozygous. The fetus was shown to be heterozygous as well, showing it had inherited at least one normal p67phox gene from the father and that it was predicted to have a normal phenotype. Cord blood samples at birth showed normal oxidative function. Amplification allows rapid detection of the inheritance pattern for fetal diagnosis in informative families. We report the genomic structure of p67phox and an amplification-based method for detection of the marker on chromosome 1q25, used here for prenatal diagnosis of CGD.     

Young porcine endocrine pancreatic islets cultured in fibrin show improved resistance toward hydrogen peroxide

Aim: To study the protective effect of a fibrin scaffold toward embedded young porcine endocrine pancreatic islets from hydrogen peroxide within the context of islet encapsulation in transplantation. Methods: After isolation and in vitro maturation, groups of 200 young porcine islet equivalents (IEQ) were embedded in a 200 µL fibrin gel and exposed to 2 concentrations (10 and 100 µM) of hydrogen peroxide (H₂O₂) to investigate the ability of fibrin to protect islets against apoptotic stimuli. As a control, young porcine islets were seeded in tissue culture polystyrene (TCPS) well plates and exposed to the same H₂O₂ concentrations. Islet integrity, viability and function were then investigated. Results: Morphologically, the integrity of islets embedded in fibrin gels was better preserved compared with that of islets cultured in TCPS plates, when exposed to H₂O₂. Immunofluorescence staining showed that insulin and glucagon expression was higher in islets cultured in fibrin. Overall, H₂O₂ incubation led to decreased insulin and glucagon expression. A TUNEL assay revealed elevated numbers of apoptotic cells for islets cultured in TCPS plates when compared with those embedded in fibrin. Islets cultured in TCPS plates and exposed to H₂O₂ had diminished ability to secrete insulin in response to glucose stimulation, whereas islets embedded in fibrin maintained their glucose responsiveness. Insulin trapped in fibrin was extracted and quantified, revealing insulin in the extract. Conclusions/Interpretation: Fibrin has a protective effect on young porcine endocrine pancreatic islets exposed to hydrogen peroxide.     

Non-coronary sinus of Valsalva aneurysm diagnosed after a road traffic accident

A 38 year old man with a huge unruptured sinus of Valsalva aneurysm, complicated with severe valvar aortic regurgitation, is described. The aneurysm was detected by echocardiography in the asymptomatic patient who presented with an intense precordial diastolic rumble after a road traffic accident. The patient had successful surgery for the aneurysm and aortic valve replacement. Possible aetiologies for the aneurysm and a brief revision of clinical aspects and treatment are discussed.


Keywords: sinus of Valsalva aneurysm; valvar disorders; trauma     

The Austrian syndrome: a case report and review of the literature

A 61-year-old man presented with fever and altered mental status. He was intubated for respiratory distress and was found to have multilobar pneumonia for which antibiotic therapy was instituted. However, his mental status continued to deteriorate despite appropriate antibiotic therapy for his pneumonia. The results from lumar puncture revealed meningitis and endocarditis was evident on a trans-esophageal echocardiogram. His blood and respiratory cultures grew Streptococcus pneumoniae. The patient was diagnosed with Austrian syndrome. After appropriate changes to his antibiotic regimen and an aortic valve replacement, he recovered and was discharged.     

Cellular immunotherapy after allogeneic stem cell transplantation in hematologic malignancies

PURPOSE OF REVIEW: The chimeric state after allogeneic stem cell transplantation provides an ideal platform for adoptive immunotherapy of hematologic malignancies using donor-derived cells. The present review aims to summarize recent results of the transfusion of donor-derived cells with regard to the diseases treated, the cells used for treatment, and the origin of these cells. RECENT FINDINGS: The transfusion of donor lymphocytes has been studied widely, not only in patients with recurrent disease, persistent disease, and mixed chimerism but also in a variety of hematologic malignancies. Donors of lymphocytes and hematopoietic stem cells have been HLA-identical siblings, HLA-matched unrelated donors, and HLA-different haploidentical family members. A variety of cells have been used for adoptive immunotherapy, including plain lymphocytes, selected T cells, T cell lines, and T cell clones. The possible therapies have been expanded by natural killer cells and natural killer T cells as well as antibodies directing the effector cells toward the malignancy. SUMMARY: Adoptive immunotherapy in chimeras has become not only a routine form of treatment of recurrent hematologic malignancy but also a prophylactic measure in high-risk leukemia and lymphoma.     

Community‐Based Practice Experience of Unsuspected Breast Magnetic Resonance Imaging Abnormalities Evaluated With Second‐Look Sonography

Objective. The purpose of this study was to assess the utility and efficacy of second‐look breast sonography in the evaluation of abnormalities identified on presurgical breast magnetic resonance imaging (MRI) examinations. Methods. A retrospective review was performed of 152 presurgical breast MRI examinations having 196 unsuspected abnormalities to identify findings that underwent subsequent breast sonography. Eligible examinations had a suspicious abnormality identified on presurgical MRI and documentation of the location and size of the finding on MRI and subsequent second‐look sonography. Fourteen examinations not meeting the criteria were excluded, with 182 abnormalities remaining. Patient medical records were reviewed. Results. Seventy percent (128 of 182) of breast MRI lesions were visible at second‐look sonography; 30% (54 of 182) were sonographically occult. Ninety‐five percent (121 of 128) of sonographically visible abnormalities underwent breast biopsy. Pathologic examinations of sampled sonographically visible lesions revealed 39 cancers, 9 high‐risk lesions, 72 benign lesions, and 1 lesion not specified at surgery; 23% (9 of 128) of cancers were in the contralateral breast. Fifty‐four lesions were sonographically occult. Needle biopsy was performed for 93% (50 of 54) of occult lesions, revealing 8 cancers, 1 high‐risk lesion, and 41 benign lesions; 3 of the benign lesions did not have sufficient pathologic specimens but were benign at follow‐up. Magnetic resonance imaging guidance was used in 86% (43 of 50) of these biopsies. One contralateral cancer was identified in the sonographically occult subset. Of the 182 lesions that underwent second‐look sonography, 20% (36 of 182) had a change in management. Conclusions. Second‐look sonography has value in the evaluation of abnormalities found on breast MRI. We found enhancements in 70% (128 of 182), yielding 39 cancers.     

Vascular compression of the oculomotor nerve disclosed by thin-slice magnetic resonance imaging

Purpose: To describe the thin-slice magnetic resonance imaging features of vascular compressive oculomotor nerve paresis.Methods: We performed thin-slice (2 mm thick) magnetic resonance imaging of the brainstem in a 74-year-old woman with right partial oculomotor nerve paresis using spoiled gradient recalled acquisition in the steady state.Results: Thin-slice magnetic resonance images disclosed that the right oculomotor nerve was compressed and dislocated superiorly and laterally by the tortuous basilar artery. No other abnormalities were observed.Conclusion: This is the first case report of vascular compressive oculomotor nerve paresis disclosed by thin-slice magnetic resonance imaging.     

Blood preservation. XXXIV. DHA maintains 2,3-DPG and its adverse effect on ATP is reversed with extra phosphate

We have found that the addition of 10 mM inorganic phosphate to DHA in CPD-adenine maintains ATP levels at normal or higher than normal values for six weeks of storage. 2,3-DPG values are slightly lowered by the extra phosphate, but are still maintained at approximately half normal for four weeks by the DHA. The addition of a higher phosphate concentration, 20 mM, to DHA produced lower levels of ATP and 2,3-DPG than those observed with 10 mM phosphate, although both levels were better than in the CPD-adenine control. pH values in this experiment were lowest in the three preservatives containing DHA, probably indicating increased lactate production due to metabolism of this triose sugar, in addition to dextrose present in CPD.