(Micro)spectroscopic analyses of particle size dependence on arsenic distribution and speciation in mine wastes.

The chemical speciation and distribution of potentially toxic metal(loid)s in mine wastes is critical to assessing the risks posed by these wastes and predicting the potential bioavailability of the metal(loid)s present. Of additional potential importance is the role of particle size in the fate, transport, and toxicity of contaminated mining materials. Spectroscopic analyses of size-separated mine tailings and adjacent background samples from the Randsburg Historic Mining District, California were conducted to quantify the speciation and distribution of arsenic (As) as a function of particle size. Micro-X-ray fluorescence (µXRF) mapping of separate size fractions was used to identify multiple populations of particles with different As:Fe ratios, indicating a variety of distinct arsenic-bearing species. Bulk extended X-ray absorption fine structure (EXAFS) spectroscopy identified phases including arseniosiderite, Ca2Fe3(3+)(AsO4)3O3·3H2O, and As(V) sorbed to iron hydroxides (ferrihydrite, goethite), confirming a strong statistical correlation between arsenic and iron observed in both µXRF studies and bulk chemical analyses. Differences in As speciation between the mine tailings and background samples also suggest that weathering of crystalline As-bearing phases in tailings leads to sorption of dissolved arsenic to iron hydroxides in nontailings background material.

Crack cocaine induced upper airway injury.

The paper describes the presentation and management of patients presenting with crack cocaine induced upper airway injury. The study involved a retrospective clinical series of six patients with crack cocaine induced upper airway injury. Demographics, symptoms, physical exam, flexible laryngoscopy findings, treatment and intervention were recorded. All patients with crack cocaine induced thermal injury presented with mouth or throat pain plus at least one other laryngeal symptom, such as globus sensation, dysphagia or throat tightness. On physical exam, the supraglottis was the most common subsite of endolaryngeal injury. The only statistically significant finding was the number of subsites on initial physical exam and flexible laryngoscopy and need for airway intervention (p = 0.001). Airway intervention was required in one patient, while the remaining patients were closely observed until resolution of symptoms. Upper airway injury should be suspected in patients who present with pain and laryngeal symptoms after smoking crack cocaine.

Nous décrivons la clinique et la prise en charge des patients souffrant de lésions respiratoires supérieures liées à l'usage de Crack, en nous basant sur une série rétrospective de 6 cas. Nous avons colligé la démographie, les signes et symptômes, les données cliniques et endoscopiques ainsi que le traitement. Tous souffraient de douleur bucco- pharyngées et au moins d'un signe laryngé parmi sensation de gonflement, dysphagie ou sensation d'étouffement. Á l'examen, la zone supra- glottique était la plus communément atteinte. Le nombre de zones atteintes corrélait positivement (p = 0,001) à la nécessité d'une intervention sur les voies aériennes, qui n'a cependant été nécessaire que pour 1 patient, les autres ayant été simplement surveillés jusqu'à disparition des symptômes. Une atteinte des voies aériennes supérieures doit être soupçonnée devant un patient se présentant avec des douleurs et des signes laryngés après avoir fumé du crack.

Treatment of ulcerative endobronchial tuberculosis and bronchial stenosis with aerosolized streptomycin and steroids.

OBJECTIVES: Endobronchial tuberculosis (EBTB) is defined as a tuberculous infection of the tracheobronchial tree. It has been reported that aerosolized therapy with streptomycin and steroids is useful for EBTB; however, the effectiveness of this therapy for bronchial stenosis has yet to be clarified. This study was undertaken to determine the effectiveness of aerosol therapy in the treatment of bronchial stenosis due to EBTB. DESIGN: An observational, historical, controlled comparative study. Retrospective analysis of 27 patients treated with conventional therapy, and prospective analysis of 30 patients treated with aerosol therapy. METHOD AND PATIENTS: Flexible bronchoscopy was performed at least twice in 57 patients with ulcerative EBTB, in whom the degree of bronchial stenosis between the first and last bronchoscopic examinations was estimated. Bronchial stenosis was graded as minimal, mild, moderate, severe or obstructive, and the follow-up of bronchial stenosis assessed as aggravation, no change or improvement. RESULTS: Conventional therapies led to aggravation in 13 patients, no change in 13 patients, and improvement in one patient. Aerosol therapy led to no change in 27 patients, and improvement in three patients. No patients developed aggravation. The differences between the therapeutic groups were significant. CONCLUSION: Aerosol therapy helps to prevent progressively severe bronchial stenosis due to EBTB.

Potential use of Amplicor PCR kit in diagnosing pulmonary tuberculosis from gastric aspirate.

Polymerase chain reaction (PCR) detection of mycobacteria from gastric aspirate for the diagnosis of tuberculosis is not fully evaluated up to now. A total of 116 gastric aspirate specimens were collected from patients with suspected pulmonary tuberculosis. The breakdown of diagnosis was 67 pulmonary tuberculosis, 16 nontuberculous mycobacterial infection, 5 extra pulmonary tuberculosis, and 28 other lung diseases. The conventional methods were shown to have a sensitivity of 47.8% and a specificity of 79.6%; on the other hand, Amplicor had 34.9% and 97.0%, respectively. The Amplicor provided a more rapid and specific method for diagnosing tuberculosis and was more useful than the conventional.

Effect of macrolide antibiotics on neutrophil function in human peripheral blood.

Since "small-dose and long-term" administration of erythromycin (EM) was shown to be efficacious in the treatment of chronic respiratory disease, the modulation of host defense responses by EM has attracted much attention. Although there is considerable controversy, it was recently demonstrated that EM activity reduces neutrophil function. In this study, we investigated the in vitro effects of the macrolides erythromycin (EM), a 14-membered ring, azithromycin (AZM), a 15-membered ring and rokitamycin (RKM), a 16-membered ring macrolide, on neutrophil function. The DCFH-DA method and cytochrome C method were used for assay of active oxygen generation and the Boyden-chamber method was used for assay of chemotaxis. EM and AZM, both of which have been shown to be clinically effective in the treatment of Diffuse panbronchiolitis (DPB), significantly suppressed active oxygen generation and chemotaxis of neutrophils at low concentrations equivalent to therapeutic doses (0.5 approximately 1.0 microgram/ml, p < 0.05), whereas the clinically ineffective RKM did not. The in vitro inhibitory effects of EM and AZM on active oxygen generation and chemotaxis of neutrophils demonstrated in the present study may be responsible for the therapeutic efficacy of these 14-membered and 15-membered ring macrolides in the treatment of DPB patients.

[Effect of macrolides on cytokine mRNA expression in human whole blood model].

Recently, low dose and long term use of Macrolides (Mls) has been reported to be effective in treatment of chronic lower respiratory tract infections, however its mechanism is still obscure. We evaluated the effect of Mls (EM, AZM, RKM) on cytokine mRNA expressions. We preincubated the whole blood with several concentrations of Mls and removed the Mls and then stimulated human whole blood with LPS as an experimental vivo model. In order to examine cytokine mRNA expressions, we used the RT-PCR method. Cytokine mRNA expressions were suppressed significantly (p < 0.05) by pretreatment with EM, AZM; moreover, the suppression was peaked at low concentrations (0.04 approximately 0.2 microgram/ml). Although, Cytokine mRNA expressions were not suppressed by pretreatment with RKM. These results suggest that EM, AZM have suppression on Cytokine mRNA expressions, and consequently, this suppression has a reasonable effect for DPB patients.

[Familial cases of spastic paraparesis, mental disturbance and thinning of the corpus callosum].

We reported a family in which two brothers and one sister out of five siblings were affected by a neurological disease showing the following clinical manifestations: 1) intellectual disturbance with relative preservation of memory and orientation probably developed on child food, 2) spastic paraparesis beginning at the age of about 20 years, 3) mild peripheral neuropathy and cerebellar sign. Their clinical courses were stereotyped, and so much the worse in elder patients. Two of them were investigated in detail. Laboratory findings including chromosomal analysis, amino acid analysis and thyroid function were normal. HTLV-1 antibody was negative. Several lymphocytes lysosomal enzymes including beta-hexosaminidase and arylsulfatase A and serum very long fatty acids were also within normal range. CT and MRI showed characteristic thinning of corpus callosum, dominant in anterior portion. However, changes in intensity of white matter in T2 weighted image were not so prominent. In the older patient, more mentally deteriorated, were demonstrated hypoperfusion in the fronto-parietal lobes by SPECT and slow wave bursts dominant in the same region by EEG. Therefore, we considered that the change of corpus callosum was hypoplasia, but not atrophy, and it may provoke dysfunction of relevant nervous system. Family cases of such clinical feature were rare. We could confirm only three families in literatures, all of them were Japanese.

[Isolated fracture of the lateral mass of the atlas: a case report].

Isolated fracture of the lateral mass of the atlas is extremely rare. The authors report such a case because of its rarity and to emphasize the usefulness of computed tomography (CT) for its diagnosis. The case was that of a 63-year-old male, who had been hit on his left parietal region by a board falling from behind, and which forced him to hyperflex his neck. He complained of neck pain on arrival at our hospital without any resulting neurological deficits. Routine plain cervical spine films were normal, but CT scan revealed a vertical fracture of the lateral mass of the atlas. He was placed in a Halo brace for several months, and after 3 months the fracture was seen, by CT scan, to have healed without complications. Fractures of the atlas are uncommon. They comprise 2-13% of all fractures of the cervical spine, and about 1.3% of the fractures of the entire spinal column. An isolated fracture of the lateral mass of the atlas has been reported only in seven cases including our case previously and this is the first case in which CT scan could make the diagnosis. We emphasize that CT scan is a most useful tool for the diagnosis of the fracture.

Ink4a and Arf are crucial factors in the determination of the cell of origin and the therapeutic sensitivity of Myc-induced mouse lymphoid tumor.

The cell of origin of tumors and the factors determining the cell of origin remain unclear. In this study, a mouse model of precursor B acute lymphoblastic leukemia/lymphoma (pre-B ALL/LBL) was established by retroviral transduction of Myc genes (N-Myc or c-Myc) into mouse bone marrow cells. Hematopoietic stem cells (HSCs) exhibited the highest susceptibility to N-Myc-induced pre-B ALL/LBL versus lymphoid progenitors, myeloid progenitors and committed progenitor B cells. N-Myc was able to induce pre-B ALL/LBL directly from progenitor B cells in the absence of Ink4a and Arf. Arf was expressed higher in progenitor B cells than Ink4a. In addition, N-Myc induced pre-B ALL/LBL from Arf(-/-) progenitor B cells suggesting that Arf has a predominant role in determining the cell of origin of pre-B ALL/LBL. Tumor cells derived from Ink4a/Arf(-/-) progenitor B cells exhibited a higher rate of proliferation and were more chemoresistant than those derived from wild-type HSCs. Furthermore, the Mdm2 inhibitor Nutlin-3 restored p53 and induced massive apoptosis in mouse pre-B ALL/LBL cells derived from Ink4a/Arf(-/-) cells and human B-ALL cell lines lacking Ink4a and Arf expression, suggesting that Mdm2 inhibition may be a novel therapeutic approach to the treatment of Ink4a/Arf(-/-) B-ALL/LBL, such as is frequently found in Ph(+) ALL and relapsed ALL. Collectively, these findings indicate that Ink4a and Arf are critical determining factors of the cell of origin and the therapeutic sensitivity of Myc-induced lymphoid tumors.

c-MYC overexpression with loss of Ink4a/Arf transforms bone marrow stromal cells into osteosarcoma accompanied by loss of adipogenesis.

The development of cancer is due to the growth and proliferation of transformed normal cells. Recent evidence suggests that the nature of oncogenic stress and the state of the cell of origin critically affect both tumorigenic activity and tumor histological type. However, this mechanistic relationship in mesenchymal tumors is currently largely unexplored. To clarify these issues, we established a mouse osteosarcoma (OS) model through overexpression of c-MYC in bone marrow stromal cells (BMSCs) derived from Ink4a/Arf (-/-) mice. Single-cell cloning revealed that c-MYC-expressing BMSCs are composed of two distinctly different clones: highly tumorigenic cells, similar to bipotent-committed osteochondral progenitor cells, and low-tumorigenic tripotent cells, similar to mesenchymal stem cells (MSCs). It is noteworthy that both bipotent and tripotent cells were capable of generating histologically similar, lethal OS, suggesting that both committed progenitor cells and MSCs can become OS cells of origin. Shifting mesenchymal differentiation by depleting PPARγ in tripotent MSC-like cells and overexpressing PPARγ in bipotent cells affected cell proliferation and tumorigenic activity. Our findings indicate that differentiation potential has a key role in OS tumorigenic activity, and that the suppression of adipogenic ability is a critical factor for the development of OS.

[Effects of erythromycin on H2O2 generation by neutrophils].

Low-dose long-term erythromycin therapy has been reported to be effective in diffuse panbronchiolitis, but the mode of action remains obscure. We therefore evaluated the effect of erythromycin the generation of H2O2 by neutrophils. In vitro, erythromycin (0.1, 1.0, and 20 micrograms/ml) suppressed both spontaneous and PMA-stimulated H2O2 generation. H2O2 generation by neutrophils obtained from peripheral blood and from bronchoalveolar lavage fluid from patients with diffuse panbronchiolitis was higher than that from healthy controls. After erythromycin therapy, H2O2 generation by neutrophils was lower. Compared with the control, H2O2 generation by peripheral neutrophils was low in the patients who responded clinically to erythromycin therapy, but was high in those who did not respond. These results suggest that at least some of the therapeutic effect of erythromycin in patients with diffuse panbronchiolitis is due to reduction in H2O2 generation by neutrophils.

[Very rare case of adenoid cystic carcinoma of the hypopharynx].

We experienced a case of adenoid cystic carcinoma (cribriform type) of the hypopharynx treated with radiation followed by total laryngectomy and bilateral radical neck dissection. There have been no reports of adenoid cystic carcinoma of the hypopharynx in the last 30 years. In this case, the primary tumor and lymph node metastases, of the neck responded well to radiation therapy. Residual disease of the primary tumor and lymph node metastases, after a dose delivery of 50 Gy, were removed by radical surgery.