Single-sperm typing: determination of genetic distance between the G gamma-globin and parathyroid hormone loci by using the polymerase chain reaction and allele-specific oligomers.

The frequency of recombination between the G gamma-globin (HBG2) and parathyroid hormone (PTH) loci on the short arm of human chromosome 11 was estimated by typing greater than 700 single-sperm samples from two males. The sperm-typing technique employed involves the polymerase chain reaction and allele-specific oligonucleotide hybridization. Our maximum likelihood recombination fraction estimate of 0.16 (95%) confidence interval, 0.13-0.19) falls well within previous estimates based on family studies. With current technology and a sample size of 1000 sperm, recombination fractions down to approximately 0.009 can be estimated with statistical reliability; with a sample size of 5000 sperm, this value drops to about 0.004. Reasonable technological improvements could result in the detection of recombination frequencies less than 0.001.     

Tendon-to-bone healing of a semitendinosus tendon autograft used for ACL reconstruction in a sheep model

Anterior cruciate ligament (ACL) reconstruction was performed in a single hind limb of 30 sheep using a doubled semitendinosus tendon graft. Three additional animals were used as controls. Histologic and biomechanical analysis was performed from 4-52 weeks postoperatively. Perpendicular collagen fibers were found connecting the tendon graft to the bone tunnels at 8 weeks. These fibers were seen circumferentially at 12 weeks. By 24 weeks, the bone tunnel was well-defined, and no further changes were observed at 52 weeks. Tendon incorporation within the femoral and tibial tunnels was similar at each interval. Although the small sample size did not permit statistical testing, the reconstruction strength was similar up to 12 weeks (15%-19% of controls). This increased at 24 (28%) and 52 (40%) weeks. The stiffness primarily increased from 4-8 weeks (18%-39%) and 24-52 weeks (52%-82%). Up to 12 weeks, failures occurred by graft pull-out from the bone tunnel. All 24- and 52-week specimens ruptured through the intra-articular portion of the graft, further indicating sufficient graft incorporation within the bone tunnels.     

Natural history of a hamstring tendon autograft used for anterior cruciate ligament reconstruction in a sheep model

The purpose of this study was to describe the histologic structure of the intraarticular segment of a semitendinosus tendon autograft used for anterior cruciate ligament reconstruction over the first year after surgery. We performed an anterior cruciate ligament reconstruction in a single hindlimb of 11 sheep using a doubled semitendinosus tendon autograft secured to the femur with an endoscopic button and polyester tape and to the tibia with sutures tied around a screw. The histologic structure of the intraarticular segment of the graft at 4, 8, 12, 24, and 52 weeks after surgery was compared with that of the normal semitendinosus tendon and anterior cruciate ligament. The random collagen fiber orientation progressed to a longitudinal orientation from the peripheral to the central areas of the graft over the initial 12 weeks after surgery. A uniform sinusoidal crimp pattern similar to that seen in the normal anterior cruciate ligament was identified under polarized light in nearly one-half of each graft by 24 weeks. Further maturation was noted at 52 weeks. Graft necrosis was not evident at any time period. This study showed that semitendinosus tendon autografts transform into a histologic structure similar to that of the normal anterior cruciate ligament over the initial year after surgery, as has been described for patellar tendon grafts.     

Examining changes in students' perception of science relevancy and their career aspirations: Integrating sustainability-oriented socio-scientific issues into general chemistry curriculum

Making science relevant to students' lives, future careers, or societies by introducing controversial socio-scientific issues in classrooms motivates students to take more active roles in learning science. This study explored the influence of integrating two sustainability-oriented socio-scientific issues (SOS₂Is) - alternative energies and nanotechnology-into the General Chemistry curriculum on 743 students' career aspirations and perceptions of science relevancy. For the presentation of topics, two learning environments on Prezi were prepared. The participants were guided to explore these learning environments that focused on pros and cons of each topic, including environmental and health hazards of technological developments. In addition, students were encouraged to link these discussions to sustainability issues in the context of the UN SDGs. The analysis of Changes in Attitude Towards the Relevancy of Science and Career Aspirations surveys indicated that the interventions improved students' perception of science relevancy and altered their career aspirations in many areas, regardless of their socioeconomic status and ethnic background. This study provides empirical evidence for the effectiveness of discussions around socio-scientific issues in changing students’ perceptions of science and career aspirations and recommends practical methods to encourage students to become global and scientifically literate citizens.     

Pediatric Burkitt's Lymphoma and Diffuse B-Cell Lymphoma: Are Surveillance Scans Required?

Outcomes in pediatric B-Non-Hodgkin Lymphoma (B NHL) have improved with intensive chemotherapy protocols, with long-term survival now over 80%. However, long-term adverse effects of therapy and poor outcomes for patients who relapse remain challenges. In this study, we aimed to evaluate the potential risks and benefits of routine relapse surveillance imaging after the completion of therapy. We reviewed 44 B NHL patients diagnosed and treated at Texas Children's Cancer Center in the period between 2000 to 2011. All cross-sectional diagnostic imaging examinations performed for disease assessment after completion of chemotherapy were reviewed and cumulative radiation dosage from these examinations and the frequency of relapse detection by these examinations were recorded. Only 3 patients of the 44 relapsed (6.8%), though none of the relapses were initially diagnosed by computed tomography (CT) or fludeoxyglucose positron emission tomography (FDG-PET) scans. Median effective dose of ionizing radiation per patient was 40.3 mSv with an average of 49.1 mSv (range 0–276 mSv). This single-institution study highlights the low relapse rate in pediatric B-NHL with complete response at the end of therapy, the low sensitivity of early detection of relapse with surveillance CT or FDG-PET imaging, and the costs and potential increased risk of secondary malignancies from cumulative radiation exposure from surveillance imaging. We propose that routine surveillance CT or FDG-PET scans for these patients may not be necessary.     

Selective coronary angiography via antegrade venous route in congenital cyanotic heart disease

An antegrade venous technique was utilised to perform selective coronary angiography in cyanotic infants and children. The procedure was successful in 88% (37/42) cases and excellent quality angiograms were recorded. The importance of proper catheter selection and details of the technique are discussed. © 1993 Wiley-Liss, Inc.     

A phase I study of bexarotene, a retinoic X receptor agonist, in non-M3 acute myeloid leukemia

PURPOSE: Bexarotene is a retinoic X receptor agonist that has been shown in vitro to inhibit growth and induce differentiation of myeloid leukemic cell lines. We therefore conducted a phase I dose escalation study to assess the maximum tolerated dose, toxicities, and activity of bexarotene in patients with non-M3 acute myeloid leukemia (AML). EXPERIMENTAL DESIGN: We enrolled patients with active non-M3 AML who had either relapsed or refractory disease or were not eligible for standard cytotoxic chemotherapy. Cohorts of three to six patients received escalating doses of daily oral bexarotene ranging from 100 to 400 mg/m(2) until evidence of disease progression or unacceptable adverse events occurred. RESULTS: Twenty-seven patients, with median age of 69 years (range, 51-82 years), were treated. Twenty-four (89%) patients had undergone prior chemotherapy. At the highest dose level tested (400 mg/m(2)), three of six patients had to reduce their dose of bexarotene due to grade 3 adverse events. The maximum tolerable dose of bexarotene was determined to be 300 mg/m(2). Clinical activity was manifested by 4 (15%) patients with reduction in bone marrow blasts to 1 year while taking bexarotene. Leukemic blast differentiation was suggested by the presence of the leukemic cytogenetic abnormality in mature circulating granulocytes and the occurrence of differentiation syndrome. CONCLUSIONS: The recommended dose of bexarotene for future studies is 300 mg/m(2)/d. Bexarotene is well tolerated in patients with non-M3 AML and has evidence of antileukemic activity.     

Evidence of gray matter reduction and dysfunction in chromosome 22q11.2 deletion syndrome

Chromosome 22q11.2 deletion syndrome (22q11DS) is associated with cognitive deficits and morphometric brain abnormalities in childhood and a markedly elevated risk of schizophrenia in adolescence/early adulthood. Determining the relationship between neurocognition and neuroimaging findings would yield crucial information about childhood neurodevelopment and provide a basis for the study of the trajectory that occurs on the pathway to psychosis. We compared morphometric brain findings between non-psychotic children with 22q11DS (n = 22) and healthy controls (n = 16), and examined the association between neurocognitive functioning and morphometric brain findings. Volumetric regional gray matter differences between the 22q11DS and control subjects were measured, and correlations of the regional gray matter volumes and neurocognition were performed. Children with 22q11DS demonstrated reductions in gray matter in several brain regions, chiefly the frontal cortices, the cingulate gyrus and the cerebellum. The volumetric reductions in these salient areas were associated with poor performance in sustained attention, executive function and verbal memory; however, the relation of brain volume with cognitive performance did not differ between the patient and control groups. Thus, children with 22q11DS demonstrate gray matter reductions in multiple brain regions that are thought to be relevant to schizophrenia. The correlation of these volumetric reductions with poor neurocognition indicates that these brain regions may mediate higher neurocognitive functions implicated in schizophrenia.     

Correlation of MR imaging findings with intraoperative findings after cervical spine trauma

BACKGROUND AND PURPOSE: There are limited data correlating MR imaging and anatomic findings of ligamentous injury in cervical spine trauma. This study compares acute MR imaging with surgical observations of disk/ligamentous injury after blunt cervical trauma. MATERIALS AND METHODS: Consecutive patients with acute cervical spine trauma who underwent preoperative MR imaging and surgery from 1998 to 2001 were identified. MR imaging was obtained within 48 hours of injury for most patients. All scans included sagittal T1, T2 fat-saturated, and short tau inversion recovery sequences. At surgery, extent of injury at the operated level was recorded on a standardized form for either anterior or posterior structures or both depending upon the operative approach. MR examinations were separately evaluated by 2 readers blinded to the intraoperative findings. Radiologic and surgical findings were then correlated. RESULTS: Of 31 patients, an anterior surgical approach was chosen in 17 patients and a posterior approach in 13 patients. In one patient anterior and posterior approaches were utilized. Seventy-one percent of patients had spinal cord injury on MR imaging. MR imaging was highly sensitive for injury to disk (93%), posterior longitudinal ligament (93%), and interspinous soft tissues (100%), but it was less sensitive for injury to the anterior longitudinal ligament (71%) and ligamentum flavum (67%). For most ligamentous structures, there was limited agreement between specific MR imaging findings and injury at surgery. CONCLUSION: In acute cervical spine trauma, MR imaging has moderate to high sensitivity for injury to specific ligamentous structures but limited agreement between specific MR imaging findings and injury at surgery. MR imaging may overestimate the extent of disruptive injury when compared with intraoperative findings, with potential clinical consequences.     

Evidence of myeloid differentiation in non-M3 acute myeloid leukemia treated with the retinoid X receptor agonist bexarotene

All-trans-retinoic acid has dramatically changed the treatment paradigm for acute promyelocytic leukemia, however, it has no significant activity in non-M3 acute myeloid leukemia (AML). In vitro, bexarotene, a retinoid X receptor agonist inhibits the proliferation of non-M3 AML cell lines and induces differentiation of leukemic blasts from patients. We hypothesized that there may be similar activity in patients with AML. We report on two patients with relapsed or refractory non-M3 AML treated with bexarotene monotherapy. After initiating treatment, both patients showed leukemic differentiation in their peripheral blood and reduction in bone marrow blasts to less than 5%. One patient had a significant improvement in her platelet count with loss of platelet transfusion needs. Differentiation syndrome occurred in one patient and was successfully treated with steroids and discontinuation of bexarotene. These data suggest that bexarotene has clinical activity in non-M3 AML and may be able to induce myeloid differentiation in vivo.