Thoracic outlet syndrome: evaluation with CT

Diagnosis of the thoracic outlet syndrome is often difficult, particularly in patients without osseous abnormalities on plain radiographs. The radiographic and computed tomographic (CT) findings were reviewed from 27 patients with thoracic outlet syndrome and 21 normal subjects. The plain radiographs and CT scans were assessed by two independent observers without awareness of the clinical history. Fifteen patients with thoracic outlet syndrome had osseous abnormalities (anomalous cervical ribs; abnormally long, drooping C-7 transverse processes) identifiable on plain radiographs. CT did not provide further diagnostic information in the patients with abnormal radiographs. Eight of 12 patients (66%) with normal plain radiographs had abnormal findings on CT scans, consisting of impingement of the C-7 transverse process on the scalene triangle or anteromedial aspect of the middle scalene muscle. Only two of 21 control patients (9.5%) displayed this CT abnormality (P less than .01). CT may be useful in patients with symptoms suggestive of thoracic outlet syndrome and no osseous abnormalities on plain radiographs.     

Tongue and oropharynx: findings on MR imaging

Ten healthy subjects and 44 patients with diseases of the tongue or oropharynx were studied with magnetic resonance (MR) imaging. Axial, coronal, and sagittal images with a thickness of 4 mm were obtained with a pixel size of 0.75 X 0.75 mm on a 256 matrix. Nineteen of the patients underwent computed tomography (CT). Nine of those patients later had surgery, and the specimens were obtained for organ sectioning. These three studies as well as clinical history and physical examination findings were correlated. MR imaging was equal to or better than CT in those patients having both examinations. However, neither CT nor MR allowed recognition of histologic features or detection of microscopic spread of disease. Direct coronal and sagittal imaging planes on MR imaging allowed visualization of intrinsic tongue musculature, not possible with CT; this was important in recognizing subtle tumor extension. For these reasons, MR is the imaging method of choice for studying diseases of the tongue and oropharynx.     

Development of specific receptors for N-formylated chemotactic peptides in a human monocyte cell line stimulated with lymphokines

A human monocyte-like cell line, U937, when grown in continuous culture, does not secrete lysosomal enzymes or migrate towards chemotactic factors. When the cells are stimulated by lymphokines, however, they develop the ability both to migrate directionally and to secrete enzymes in response to several types of chemoattractants. The development, by stimulated cells, of chemotactic and secretory responses to one class of chemoattractants, the N- formylated peptides, is accompanied by the appearance on the cells of specific binding sites for these substances. Using tritiated N-formyl- methionyl-leueyl-phenylalanine (fMet-Leu-[(3)H]Phe) as a ligand, it was determined that unstimulated U937 cells possess no detectable binding sites. However, after stimulation with lymphocyte culture supernates for 24, 48, and 72 h, they developed 4,505 (+/-) 1,138, 22,150(+/-) 4,030, and 37,200 (+/-) 8,000 sites/cell, respectively. The dissociation constants for the interaction of fMet-Leu-[SH]Phe with the binding sites were approximately the same regardless of stimulation time and ranged between 15 and 30 nM. The binding of fMet-Leu-[(3)H]Phe by stimulated U937 cells was rapid and readily reversed by the addition of a large excess of unlabeled peptide. The affinity of a series of N-formylated peptides for binding to U937 cells exactly reflected the potency of the peptides in inducing lysosomal enzyme secretion and chemotaxis. The availability of a continuous human monocytic cell line that can be induced to express receptors for N-formylated peptides will provide a useful tool not only for the characterization of such receptors but also for the delineation of regulatory mechanisms involved in cellular differentiation and the chemotactic response.     

Plasma homocysteine, a risk factor for cardiovascular disease, is lowered by physiological doses of folic acid

Elevated plasma homocysteine, an independent risk factor for cardiovascular disease (CVD) can be lowered by administration of pharmacological doses of folic acid. The effect of lower doses in apparently normal subjects is currently unknown but is highly relevant to the question of food fortification. Healthy male volunteers (n = 30) participated in a chronic intervention study (26 weeks). Folic acid supplements were administered daily at doses increasing from 100 micrograms (6 weeks), to 200 micrograms (6 weeks), to 400 micrograms (14 weeks). Fasting blood samples collected before, during and 10 weeks post intervention were analysed for plasma homocysteine, serum and red- cell folate levels. Results, expressed as tertiles of baseline plasma homocysteine concentration, showed significant (p < or = 0.001) homocysteine lowering in the top (10.90 +/- 0.83 mumol/l) and middle (9.11 +/- 0.49 mumol/l) tertiles only. In the low tertile, where the mean baseline homocysteine level was 7.07 +/- 0.84 mumol/l, no significant response was observed. Of the three folic acid doses, 200 micrograms appeared to be as effective as 400 micrograms, while 100 micrograms was clearly not optimal. There is thus a minimal level of plasma homocysteine below which folic acid has no further lowering effect, probably because an optimal folate status has been reached. A dose as low as 200 micrograms/day of folic acid is effective in lowering plasma homocysteine concentrations in apparently normal subjects. Any public health programme for lowering homocysteine levels, with the goal of diminishing CVD risk, should not be based on unnecessarily high doses of folic acid.      

Multiple granular cell tumors are an associated feature of LEOPARD syndrome caused by mutation in PTPN11

We report a patient with a clinical and molecular diagnosis of LEOPARD syndrome (LS) associated with multiple granular cell tumors (MGCT). Bidirectional sequencing of exons 7, 12, and 13 of the PTPN11 gene revealed the T468M missense mutation in exon 12. This mutation has been previously reported in patients with LS. To our knowledge, this is the first report of MGCT associated with molecularly characterized LS and provides the first molecular evidence linking granular cell tumors (GCT) to the Ras/mitogen-activated protein (MAP) kinase pathway. We propose that MGCT can be associated with LS. Analysis of GCT from this case tested negatively for loss of heterozygosity (LOH) at the PTPN11 and NF1 loci and did not show deletions of the PTEN gene. The absence of LOH of PTPN11 supports published functional data that T468M is a dominant-negative mutation.     

Occult malignant breast lesions in 114 patients: relationship to age and the presence of microcalcifications

This study evaluates the mammographic findings in 352 patients, aged 30-85 years, who underwent spot localization and biopsy for evaluation of nonpalpable breast abnormalities. Malignancy was found at biopsy in 114 cases. The mammographic appearance (specifically, whether grouped microcalcifications, mass, or both were present) was correlated with patient age and histologic findings (specifically, whether the pathologic changes were infiltrating or noninfiltrating in nature). The prevalence of malignant conditions increased directly with age. The presence of grouped microcalcifications as the sole indicator of malignancy was seen in 100% (seven of seven) of the patients in the 30-39-year age group, 64% (18 of 28) in the 40-49-year age group, 37% (11 of 30) in the 50-59-year age group, 30% (seven of 23) in the 60-69-year age group, and 23% (six of 26) in the 70-85-year age group. Of the 49 tumors that were manifested solely as microcalcifications, 34 (69%) were noninfiltrating. The finding of grouped microcalcifications should be aggressively investigated, since it may indicate noninfiltrating carcinoma in an early stage, when the potential for cure is greatest.     

Does Physical Activity in Adolescence Have Site‐Specific and Sex‐Specific Benefits on Young Adult Bone Size,Content, and Estimated Strength?

The long‐term benefits of habitual physical activity during adolescence on adult bone structure and strength are poorly understood. We investigated whether physically active adolescents had greater bone size, density, content, and estimated bone strength in young adulthood when compared to their peers who were inactive during adolescence. Peripheral quantitative computed tomography (pQCT) was used to measure the tibia and radius of 122 (73 females) participants (age mean ± SD, 29.3 ± 2.3 years) of the Saskatchewan Pediatric Bone Mineral Accrual Study (PBMAS). Total bone area (ToA), cortical density (CoD), cortical area (CoA), cortical content (CoC), and estimated bone strength in torsion (SSI_p) and muscle area (MuA) were measured at the diaphyses (66% tibia and 65% radius). Total density (ToD), trabecular density (TrD), trabecular content (TrC), and estimated bone strength in compression (BSI_c) were measured at the distal ends (4%). Participants were grouped by their adolescent physical activity (PA) levels (inactive, average, and active) based on mean PA Z‐scores obtained from serial questionnaire assessments completed during adolescence. We compared adult bone outcomes across adolescent PA groups in each sex using analysis of covariance followed by post hoc pairwise comparisons with Bonferroni adjustments. When adjusted for adult height, MuA, and PA, adult males who were more physically active than their peers in adolescence had 13% greater adjusted torsional bone strength (SSI_p, p < 0.05) and 10% greater adjusted ToA (p < 0.05) at the tibia diaphysis. Females who were more active in adolescence had 10% larger adjusted CoA (p < 0.05), 12% greater adjusted CoC (p < 0.05) at the tibia diaphysis, and 3% greater adjusted TrC (p < 0.05) at the distal tibia when compared to their inactive peers. Benefits to tibia bone size, content, and strength in those who were more active during adolescence seemed to persist into young adulthood, with greater ToA and SSI_p in males, and greater CoA, CoC, and TrC in females. © 2014 American Society for Bone and Mineral Research.