Morphologic, biochemical, and cytogenetic studies of bone marrow and circulating blood cells in painters exposed to ethylene glycol ethers.

In a previous cross-sectional survey, up to 15% of shipyard painters were found to have mild anemia or granulocytopenia, mostly acquired since employment. Environmental studies had suggested a possible etiologic role for ethylene glycol ethers, solvents to which the men were heavily exposed and which have established myelotoxic potential. To exclude alternative hypotheses, examine possible common patterns of injury, and identify potential risk factors and markers for such an effect, the affected painters were further studied. The painters were matched with two groups of controls: exposed painters without evidence of hematologic abnormality on the previous survey and unexposed controls. Altogether 25 subjects were studied by histopathologic examination of bone marrow, cytogenetic studies of marrow cells, and peripheral lymphocytes and peripheral red cell studies of membrane and metabolic function. Except for an unexpected finding of a race-associated effect on marrow histology, insignificant differences were seen among the groups in terms of marrow morphology and cellularity, stem cell growth kinetics, and marrow or peripheral cytogenetics. Two metabolic abnormalities of peripheral red cells related to exposure or clinical status of the subjects were found. Pyruvate kinase, an established marker of acquired myelodysplasia, was significantly depressed in the subjects with previously abnormal counts. Although reduced glutathione levels and holoenzyme activities of glutathione reductase (GSHR) did not differ among groups, exposed subjects had decreased saturation of GSHR with flavin adenine dinucleotide which could be restored in vitro, suggesting riboflavin deficiency or impaired riboflavin metabolism. Thus, although a unique pattern of bone marrow injury by histologic or genetic assay attributable to ethylene glycol ethers was not defined, biochemical effects of possible mechanistic importance were identified. The relevance of these findings as subclinical disease markers remains to be established.     

Osteoid osteoma: radionuclide diagnosis

The double-density sign, seen on radionuclide bone scans, is described for diagnosing osteoid osteomas and for localizing the nidus. Its use in differentiating the nidus of an osteoid osteoma from osteomyelitis is also described. The utility of computed tomography in localization of the nidus is also illustrated. The double-density sign was helpful in diagnosing seven cases of surgically confirmed osteoid osteoma.     

Lymphadenopathy detected by ultrasound examination as first diagnostic hint of chronic lymphocytic leukaemia in a patient with melanoma

Recent reports indicate that patients with malignant melanoma might be at higher risk for developing a non-cutaneous unrelated second malignancy. We describe the case of a 46-year-old woman who had a malignant melanoma on her right shoulder that was treated in 1998 by surgical excision combined with axillary lymph node dissection. In 1999, ultrasound examination of peripheral lymph nodes revealed one suspicious echopoor structure in the woman's right axilla that was not palpable. Diagnostic excision and histopathological examination revealed a small B-cell lymphocytic lymphoma, and further investigations led to a diagnosis of chronic lymphocytic B-cell leukaemia (B-CLL). We would like to point out the value of high-resolution ultrasound examination in the follow-up of patients with malignant melanoma; this examination can detect early metastasis as well as other unrelated malignancies.     

Effect of vagotomy on the quantitative histological distribution of histamine and histidine decarboxylase in the rat stomach

Determinations were made of the quantitative histological distribution of histamine and histidine decarboxylase in the body of the glandular stomach of fed and 14-hr fasted rats subjected to pyloroplasty and to pyloroplasty with vagotomy for comparison with untreated rats. Pyloroplasty on fasted rats had no significant effect on the concentration of histamine which was localized predominantly in the chief cell zone. However, the superimposed vagotomy was associated with some increase in the concentration. With the fed rats, the concentration was essentially unchanged from normal in either group of operated animals and it also was about the same as that in the normal fasted group. Histidine decarboxylase activity, which was also localized predominantly in the chief cell zone, underwent an increase in concentration following pyloroplasty of the fasted rats; no additional effect was observed with added vagotomy. The higher concentration of the enzyme activity in the fed rats was markedly further elevated in both groups of operated animals but these groups did not differ significantly from one another. An explanation of the elevation of histidine decarboxylase activity following pyloroplasty requires further investigation, but the lack of effect of the superimposed vagotomy on the enzyme activity would appear to rule out direct vagal control as the sole factor in determining the enzyme function at this site.     

Hypertrophy of C-1 anterior arch: useful sign to distinguish os odontoideum from acute dens fracture

Dens fractures are often difficult to detect radiographically because of overlapping structures. The lateral radiographs were examined of all patients at the authors' institution who demonstrated an abnormal odontoid process or an abnormal anterior arch of C-1. Six patients were found: Four had os odontoideum, one had rheumatoid arthritis, and one had a congenital defect in the posterior arch of C-1. All had hypertrophy of the C-1 anterior arch on the lateral view. The width of the anterior arch of C-1 and the cortical thickness of the anterior arch in these six patients were measured and compared with the findings in a control group of 20 patients; the measurements from the six patients were found to be significantly greater. Hypertrophy of the anterior arch of C-1 is a useful sign of a chronic pathologic condition at the atlantoaxial articulation, and in the setting of acute trauma it may be an important clue that prevents unnecessary invasive treatment for a mistaken diagnosis of fractured dens.     

Glutamate acting at NMDA receptors stimulates embryonic cortical neuronal migration

During cortical development, embryonic neurons migrate from germinal zones near the ventricle into the cortical plate, where they organize into layers. Mechanisms that direct neuronal migration may include molecules that act as chemoattractants. In rats, GABA, which localizes near the target destination for migrating cortical neurons, stimulates embryonic neuronal migration in vitro. In mice, glutamate is highly localized near the target destinations for migrating cortical neurons. Glutamate-induced migration of murine embryonic cortical cells was evaluated in cell dissociates and cortical slice cultures. In dissociates, the chemotropic effects of glutamate were 10-fold greater than the effects of GABA, demonstrating that for murine cortical cells, glutamate is a more potent chemoattractant than GABA. Thus, cortical chemoattractants appear to differ between species. Micromolar glutamate stimulated neuronal chemotaxis that was mimicked by microM NMDA but not by other ionotropic glutamate receptor agonists (AMPA, kainate, quisqualate). Responding cells were primarily derived from immature cortical regions [ventricular zone (vz)/subventricular zone (svz)]. Bromodeoxyuridine (BrdU) pulse labeling of cortical slices cultured in NMDA antagonists (microM MK801 or APV) revealed that antagonist exposure blocked the migration of BrdU-positive cells from the vz/svz into the cortical plate. PCR confirmed the presence of NMDA receptor expression in vz/svz cells, whereas electrophysiology and Ca2+ imaging demonstrated that vz/svz cells exhibited physiological responses to NMDA. These studies indicate that, in mice, glutamate may serve as a chemoattractant for neurons in the developing cortex, signaling cells to migrate into the cortical plate via NMDA receptor activation.