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.     

Multiple myeloma in a patient at risk for AIDS

An increased incidence of tumors and B-cell lymphomas development has been reported in persons with or at risk for acquired immunodeficiency syndrome (AIDS). This report focuses on a 50-year-old homosexual man with HIV antibodies who met the established criteria for the diagnosis of multiple myeloma: an IgG monoclonal spike greater than 2 g/dl and a plasma cell count greater than 20% in the bone marrow aspirate. Serum protein immunoelectrophoresis showed monoclonal IgG kappa, and in the urine no excess of kappa chains was found. Laboratory data revealed a total IgG of 38 g/l, IgA of 5.2 g/l, and IgM of 2.3 g/l; the calcium level was normal; ESR was 119/130, and no plasmocytoid cells were seen in the differential count. No lytic lesions were found in the skeletal survey. The helper/suppressor T-cell ratio was depleted with 0.1 and HLA-DR was highly elevated with 56% in the immunofluorescent analysis. The development of the most differentiated B-cell tumor broadens the spectrum of B-cell neoplasias in patients with a predominant helper T-cell defect and focuses on the role of disordered immunoregulation and chronic antigenic stimulation in predisposing to B-cell malignant transformation associated with AIDS.     

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.     

Cumulative lifetime incidence of extracolonic cancers in Lynch syndrome: a report of 121 families with proven mutations

Lynch syndrome or hereditary non-polyposis colorectal cancer is caused by mutations of DNA mismatch repair (MMR) genes. The extracolonic tumour spectrum includes endometrial, ovarian, gastric, small bowel, pancreatic, hepatobiliary, brain, and urothelial neoplasms. Families were referred on the basis of clinical criteria. Tumour immunohistochemistry and microsatellite testing were performed. Appropriate patients underwent sequencing of relevant exons of the MMR genes. Proven and obligate mutation carriers and first-degree relatives (FDRs) with a Lynch syndrome spectrum cancer were considered mutation carriers, as were a proportion of untested, unaffected FDRs based on the proportion of unaffected relatives testing positive in each age group. Kaplan–Meier analysis of risk to 70 years was calculated. One hundred and eighty-four Lynch syndrome spectrum extracolonic cancers in 839 proven, obligate, or assumed mutation carriers were analysed. Cumulative risk for females of an extracolonic tumour is 47.4% (95% CI 43.9–50.8). The risk to males is 26.5% (95% CI 22.6–30.4). There was no reduction in gynaecological malignancies due to gynaecological screening (examination, transvaginal ultrasound scan, hysteroscopy and endometrial biopsy). Males have a higher risk of gastric cancer than females (p = 0.0003). Gastric cancer risk in those born after 1935 does not justify surveillance. These penetrance estimates have been corrected for ascertainment bias and are appropriate for those referred to a high-risk clinic.