Subchronic and Chronic Inhalation Toxicity of Antimony Trioxide in the Rat

Fischer 344 rats were exposed by inhalation to Sb₂O₃ (antimonytrioxide) dust at exposure levels of 0, 0.25, 1.08, 4.92, and23.46 mg/m³ for 6 hr/day, 5 days/week for 13 weeks followedby a 27-week observation period. Subsequently, an inhalationon-cogenicity study was conducted at exposure levels of 0, 0.06,0.51, and 4.50 mg/m³ for 12 months followed by a 12-month observationperiod. The Sb₂O₃ in the subchronic study had a mass medianaerodynamic diameter (MMAD) of 3.05 ± 0.21 microns (mean± SD) with a geometric standard deviation (GSD) of 1.57± 0.06. In the chronic study, the MMAD was 3.76 ±0.84 and the GSD was 1.79 ± 0.32. Except for the eyes,no adverse clinical observations were attributed to Sb₂O₃ ineither study. In the subchronic study, corneal irregularitieswere seen after about 2 weeks of exposure and did not abateduring the observation period. In the chronic study, ophthalmoscopicevaluation at 24 months revealed a dose-related increase incataracts of 11, 24, 28, and 32% (both sexes combined) for eachgroup, respectively. Body weights were significantly lower (6%)than the control group's weights in the 23.46 mg/m³ males inthe subchronic study. These rats did not recover this weightduring the 27-week observation period. Body weights of the femalesin both studies and males in the chronic study were unaffected.There were no Sb₂O₃ effects on clinical chemistry or he-matologyin either study. Mean absolute and relative lung weights weresignificantly increased in the 4.92 and 23.46 mg/m³ groups inthe subchronic study. The 23.46 mg/m³ group's lung weights didnot recover to control levels during the 27-week observationperiod. Lung weights for rats in the chronic study were unaffected.Microscopic changes in the lungs in the subchronic and chronicstudy were limited to subacute-chronic interstitial inflammation,increased numbers of alveolar-in-traalveolar macrophages, foreignmaterial in the alveolar-in-traalveolar macrophages in the peribronchialand perivascular (chronic study only) lymphoid aggregates andin the peribronchial lymph nodes, granulomatous inflammation/granulomas,and fibrosis. In the chronic study, any observed neoplasms occurredwith comparable incidence among all groups and were within thehistorical range for controls. Clearance of Sb₂O₃ from the lungwas burden dependent and was reduced by 80/ in the 4.50 mg/m³group in the chronic study. The previously reported studies,which found Sb₂O₃ to be a carcinogen, were run at higher lungburdens. Under the exposure conditions of the current study,Sb₂O₃ was not a carcinogen.     

The Effect of Etiocholanolone on Granulocyte Kinetics

The effect of etiocholanolone on granulocyte kinetics in 12 hematologicallynormal patients has been investigated using the technic of ³H-DFP labelingof autologous blood in vitro.

Baseline determinations of the total blood granulocyte pool (TBGP), thecirculating pool (CGP), and the marginated pool (MGP) were performed.The values for the total blood granulocyte pools were similar to those previously reported. Following the administration of etiocholanolone, there was a98 per cent increase in the TBGP, which was considered to be due to mobilization of granulocytes from the bone marrow reserve. There was no change inthe ratio of CGP to MGP.

These studies suggest that etiocholanolone may be a useful agent for theestimation of bone marrow reserve.

Submitted on November 21, 1966 Accepted on April 13, 1967     

Studies with the Folate Binding Protein in Chronic Granulocytic Leukaemia Cells: I. SYNTHESIS AND RELEASE OF BINDER BY CELLS IN SHORT-TERM CULTURE

Chronic granulocytic leukaemia (CGL) cells which contained a high concentration of unsaturated folate binding protein were incubated in suspension culture for a period of 5 h. Cell samples were periodically assayed for binder and these demonstrated active synthesis which was inhibited by puromycin, cyclo heximide, N-ethylmaleimide, and by incubation at 4 degrees C, but not by actinomycin D. Folate binding activity could also be demonstrated in the culture medium and this increased with the duration of incubation. This release of binder was inhibited by culturing the cells at 4 degrees C and by the addition of N-ethylmaleimide, but not by actinomycin D, puromycin, or cycloheximide. When the pre- and post-culture cell lysates were saturated with tritiated folic acid ([3H]PteGlu) and subjected to chromatography on DEAE-agrarose, approximately half of the bound folate eluted with 0.001 M phosphate buffer at pH 6.0 and the other half eluted with 0.2 M buffer at pH 7.2. The culture medium and plasma from this patient with CGL was well as serum from two normal subjects saturated with [3H]PteGlu and similarly chromatographed contained primarily the acidic binder and much less of the binder eluting with the low molarity buffer. Since a folate binding protein immunochemically similar to the binder in CGL cells has been identified in the serum of non-leukaemic subjects, these experiments suggest that the source of circulating folate binding protein may be the immature granulocyte.     

The Involvement of General Practitioners in the Care of Patients with Human Immunodeficiency Virus Infection: Current practice and Future Implications

The objective was to determine the current use of their generalpractitioner (GP) by patients with human immunodeficiency virus(HIV) infection and whether such patients would be interestedin having ‘shared care’ between a specialist HIVclinic and their GP. A questionnaire was administered to 203HIV-positive men attending the HIV outpatient clinic of a centralLondon teaching hospital. The main outcome measures were patientcharacteristics, numbers of patients registered with a GP, numbersof patients with a GP aware of their diagnosis, contacts withthe GP in the last year and level of interest and shared care.Eighty-five per cent of patients were registered with a GP ofwhom 67% knew of the diagnosis. Those diagnosed for more than2 years were significantly more likely to have an informed GP.A total of 73% of those registered had visited their GP in theprevious year although only 27% had visited for an HIV-relatedproblem. Only 19% had a GP actively involved in their HIV care.In all 51% of the patients indicated an interest in having sharedcare between the clinic and their GP. A high proportion of HIVpatients are registered with and attend a GP although they rarelyconsult for HIV-related problems. A significant proportion ofpatients expressed interest in having shared care suggestingthat there is the potential for increased GP involvement inthe care of patients with HIV infection.     

Pyoderma Gangrenosum Complicating Crohn''s Disease

A case of multiple carcinoids and cancers coexisting in the stomach and thyroid gland is presented. The multiplicity of tumors suggests a neoplastic diathesis which should alert the physician to the possibility of other independent tumors.