Occurrence of the t(2;5)(p23;q35) in non-Hodgkin's lymphoma

Primary CD30(Ki-1)-positive anaplastic large-cell lymphoma (ALCL) is considered by some to be a distinct clinicopathologic entity associated with the t(2;5) (p23;q35). However, the specificity of t(2;5) for ALCL has not been carefully studied. Therefore, we performed a detailed analysis of all cases of ALCL with abnormal cytogenetics results in the Nebraska Lymphoma Study Group registry, as well as all other cases of non-Hodgkin's lymphoma with t(2;5) in the registry. We found the t(2;5) in only five of 10 cases of ALCL, four of whom were young patients. However, we also found the t(2;5) in 11 other cases of nonanaplastic lymphoma, including eight children with typical peripheral T-cell lymphomas of various types. The t(2;5) was also found in three older adults with B-cell lymphomas of various types. Thus, the t(2;5) was not specific for CD30+ ALCL. However, t(2;5) may define a clinicopathologic entity in children and young adults characterized by variable morphologies with a T-cell or indeterminate phenotype, CD30-positivity, nodal disease with frequent extranodal involvement, advanced stage, and an excellent response to therapy, including bone marrow transplantation for relapsed disease. The clinical relevance of the t(2;5) in older patients requires further study.     

Hemorrhagic and nonhemorrhagic brain lesions: evaluation with 0.35-T fast MR imaging

Two fast magnetic resonance (MR) imaging techniques, advanced Fourier and partial-flip imaging, were used at 0.35 T to examine 21 patients with suspected intracranial lesions; the results were quantitatively compared with a conventional spin-echo study. Both of the fast MR techniques yielded a fourfold reduction in imaging time per section. The advanced Fourier sequence showed contrast that was identical to the conventional spin-echo study with signal-to-noise ratios of 58% and 57% for the first and second echoes, respectively. The partial-flip sequence showed a contrast of 109% and 57% for lesions versus substantia alba, and 107% and 78% for substantia grisea versus substantia alba relative to the first and second echoes of the conventional spin-echo study. The partial-flip sequence was particularly sensitive to magnetic susceptibility; this produced artifacts that may undermine the usefulness of partial flip for routine screening in certain parts of the brain. However, this susceptibility significantly improved the detection of intracranial hemorrhage when compared with the spin-echo sequence, particularly when combined with phase mapping of the partial-flip study.     

Fatigue in multiple sclerosis is not due to sleep apnoea

Fatigue is a frequent and disabling phenomenon among patients with multiple sclerosis (MS). Daytime sleepiness is a typical symptom of the sleep apnoea/hypopnoea syndrome due to nocturnal hypoxia and recurrent arousals causing sleep fragmentation. Since MS plaques are often found in the midbrain, brain stem and upper cervical cord on magnetic resonance imaging (MRI) we hypothesized that fatigue in MS patients might be caused by a central respiratory dysfunction. We investigated 10 patients with definite MS by oligography, two questionnaires assessing fatigue (Fatigue Severity Scale, FSS) and daytime sleepiness (Epworth Sleepiness Scale, ESS), MRI and pulmonary function tests. A total of six patients had either an elevated FSS and/or an elevated ESS. None of the six patients with an elevated FSS and/or ESS has an apnoea index > 5/hour. CT₉₀ was normal in nine patients. We conclude that fatigue and daytime sleepiness in MS cannot be explained by nocturnal apnoeas or oxygen desaturations. The Fatigue Severity Scale should be integrated to the extended Barthel index, which is a new instrument for disability assessment in MS patients.     

Genetic linkage of the tricho-dento-osseous syndrome to chromosome 17q21

Tricho-dento-osseous syndrome (TDO), MIM# 190320, is transmitted as a highly penetrant autosomal dominant trait that is characterized by variable clinical expression. The principal clinical features include kinky/curly hair in infancy, enamel hypoplasia, taurodontism, as well as increased thickness and density of cranial bones. Possible genetic linkage has been reported for TDO with the ABO blood group locus, but the gene defect remains unknown. We have identified four multiplex families (n = 63, 39 affected, 24 unaffected) from North Carolina segregating TDO. We previously have excluded a major locus for TDO in the ABO region for these families. Utilizing a genome-wide search strategy, we obtained conclusive evidence for linkage of the TDO syndrome locus to markers on chromosome 17q21 (D17S791, Z max = 10.54, Theta = 0.00) with no indication of genetic heterogeneity. Multipoint analysis suggests the TDO locus is located in a 7 cM chromosomal segment flanked by D17S932 and D17S941. This finding represents the first step towards isolation and cloning of the TDO gene. Identification of this gene has important implications for understanding normal and abnormal craniofacial development of hair, teeth and bone.      

Missense mutation in a von Willebrand factor type A domain of the alpha 3(VI) collagen gene (COL6A3) in a family with Bethlem myopathy

The Bethlem myopathy is a rare autosomal dominant proximal myopathy characterized by early childhood onset and joint contractures. Evidence for linkage and genetic heterogeneity has been established, with the majority of families linked to 21q22.3 and one large family linked to 2q37, implicating the three type VI collagen subunit genes, COL6A1 (chromosome 21), COL6A2 (chromosome 21) and COL6A3 (chromosome 2) as candidate genes. Mutations of the invariant glycine residues in the triple-helical domain-coding region of COL6A1 and COL6A2 have been reported previously in the chromosome 21-linked families. We report here the identification of a G-->A mutation in the N-terminal globular domain-coding region of COL6A3 in a large American pedigree (19 affected, 12 unaffected), leading to the substitution of glycine by glutamic acid in the N2 motif, which is homologous to the type A domains of the von Willebrand factor. This mutation segregated to all affected family members, to no unaffected family members, and was not identified in 338 unrelated Caucasian control chromosomes. Thus mutations in either the triple-helical domain or the globular domain of type VI collagen appear to cause Bethlem myopathy.      

Transition from Film to Electronic Media in the First-Year Medical School Gross Anatomy Lab

For the benefit of the first-year gross anatomy students, we digitized and published on a Web site images that had been collected over a 30-year period. We provided a CD-ROM (compact disk, read-only media) containing the image set in higher quality format to students and faculty. We supplemented basic images with hot topics such as CT angiography, virtual colonography, computer-aided diagnosis, and 3D post-processing. Full motion video and moving JPEG (Joint Photo Expert Group) animations were integrated into the atlas. On the post course questionnaire medical students reported that the images on CD-ROM were helpful during the course and for review prior to examinations. Faculty and medical students used the CD-ROM for problem-based learning sections and facilitator training. The images were clear and easily projected during review sessions and were useful for the small group sessions, where they served as examples of normal anatomy.     

The effect of a keto acid-amino acid supplement to a restricted diet on the progression of chronic renal failure

We treated 24 patients who had chronic renal failure with a low-phosphorus diet containing 20 to 30 g of mixed-quality protein, supplemented by amino acids and their keto analogues. Seventeen patients had well-defined rates of progression before treatment, as assessed by serial determinations of serum creatinine levels. By extrapolating these rates of progression, we found that 10 of the 17 (59 per cent) had a clinically important slower rise in creatinine levels during long-term treatment (average, 20 months) than predicted; none had a faster rise than predicted. Seven of the 17 patients began treatment before creatinine reached the level of 8 mg per deciliter; in six of the seven, followed for an average of 22 months, creatinine has remained at or below the level at the start of treatment. Nutrition, as assessed by body weight, nitrogen balance, serum albumin, and serum transferrin, has been well maintained. This regimen slowed or arrested the rise in creatinine levels and thus must have slowed or halted the progression of renal insufficiency in a majority of cases, especially when treatment was initiated before creatinine had reached the level of 8 mg per deciliter. The mechanism underlying this effect remains to be determined.