Skin responses to step-up and step-down heating in C3H mice.

The effects of step-up (42 leads to 44 degrees C sequence) and step-down (44 leads to 42 degrees C sequence) heating were studied on the skin of C3H/He mouse feet. Skin damage in mouse feet exposed to 44 degrees C alone became proportionally more severe with increasing exposure time, while it was slight or not observed at 42 degrees C for up to 2 hr. Preheating to 42 degrees C for 60 or 120 min (step-up) had little effect on the damage from 30-60 min exposure at 44 degrees C, but increased the damage seen with 90 min at 44 degrees C. However, skin damage was markedly enhanced by exposure to step-down heating. On the other hand, thermal resistance was induced in the mouse skin by 44 degrees C fractionated treatments. The induced thermal resistance reached a maximum with a 1 day interval, and then disappeared after a 3 day interval. In another fractionation schedule of step-down heating, the enhanced skin damage which was observed when here was no interval, recovered rapidly and attained an additive response within a 1 day interval. No thermal resistance was observed.

Doxapram hydrochloride in the treatment of acute exacerbation of chronic respiratory failure. A patient with four episodes treated without use of a respirator.

A 51-year-old woman with chronic respiratory failure (status after tuberculosis) was given an infusion of doxapram hydrochloride (1 to 2 mg/kg of body weight per hour) for four episodes of acute exacerbation of her condition. Treatment with the drug prevented worsening of hypercapnia in the four episodes, when administration of 24 percent oxygen had occasioned rises in the arterial carbon dioxide tension of 23, 10, 9, and 7 mm Hg.

Occupational asthma from cobalt sensitivity in workers exposed to hard metal dust.

Eight asthmatic patients who had no history of asthma before starting work in a hard-metal plant and eight control subjects (three atopic, three nonatopic asthmatic, and two normal volunteers) without a history of exposure to hard metal dust were subjected to provocation tests, skin tests, radioallergosorbent tests (RAST) and Farr test with cobalt. Four of the eight patients were atopic, and seven showed bronchial hyperresponsiveness to methacholine (BHR). Patch and intradermal skin tests with cobalt chloride (CoCl2) could not discriminate the patients from control subjects. All patients had positive reactions to CoCl2 in the provocation tests; two developed immediate asthmatic reaction (IAR), four late asthmatic reaction (LAR), and two dual asthmatic reaction (DAR), while the control subjects showed no reaction. Evidence of specific IgE antibodies to cobalt-conjugated human serum albumin (Co-HSA) was presented by four patients (RAST score greater than 2) based on comparison of serum samples from 60 asthmatic patients and 25 asymptomatic workers in the same plant. Positive serum samples selectively bound 57Co, and the test was blocked by nonlabled cobalt sulfate (CoSO4). These findings suggest the development of hard metal-induced asthma from cobalt sensitivity.

Thermosensitization by methylglyoxal bis(guanylhydrazone) in Chinese hamster cells.

The modification of methylglyoxal bis(guanylhydrazone) (MGBG) by 42 degrees C hyperthermia-and/or radiation-induced cell killing was examined in Chinese hamster V-79 cells. At concentrations of more than 10 microM, cell survival decreased exponentially with increased MGBG exposure times. Cell lethality of MGBG (10 microM) was not specific for cell-cycle phases tested from G1/S through G2. When cells were treated with MGBG (10 microM) for 6 hr and then exposed to 42 degrees C hyperthermia with or without a 24-hr interval, cell survival decreased markedly compared with that for 42 degrees C alone. Cells became thermosensitive after MGBG treatment. Cells exposed to MGBG (10 microM) for 6 hr before or after X irradiation were slightly radiosensitive. When X irradiation was combined with MGBG and 42 degrees C hyperthermia, cells became more radiosensitive. From these results, it is suggested that MGBG may change the intracellular state to sensitize cells to the cytotoxic action(s) of hyperthermia.

Lymphocyte transformation test with nickel in hard metal asthma: another sensitizing component of hard metal.

To determine cell-mediated immunity to nickel, another matrix in hard metal besides cobalt, lymphocyte transformation tests (LTT) with nickel were carried out in seven hard metal asthma patients all of who had reacted to cobalt chloride in the bronchial provocation tests (BPT). Immunoallergic studies prior to the present study revealed that three of the seven generated a simultaneous positive reaction in the BPT with nickel and the allergosorbent test with nickel-conjugated human serum albumin (Ni-HSA). A stimulation index in LTT indicating a positive response was defined on the basis of results from the studies in the controls. Data revealed that two of the three who showed a combination of positive bronchial and immunological reactions with nickel had a positive LTT with nickel. In the other five, peripheral lymphocytes did not proliferate in response to nickel. Thus it is suggested that cell-mediated immunity to nickel as well as cobalt is implicated in some cases associated with hard metal asthma.

Enhancement of thermal cell killing by methylglyoxal bis(guanylhydrazone) in Chinese hamster V-79 cells.

Using the method of colony formation, the modifying effect of methylglyoxal bis(guanylhydrazone) (MGBG) was examined on 44 degrees hyperthermia- and/or radiation-induced cell killing and on thermotolerance development after 44 degrees exposure in Chinese hamster V-79 cells. After exposure to MGBG (10 microM) for more than 6 hr, cells became more sensitive to 44 degrees hyperthermia. When an interval at 37 degrees (up to 24 hr) was interposed between MGBG and hyperthermic treatments, cell survival was not significantly increased, as compared with that for MGBG immediately followed by 44 degrees. Cells treated with MGBG remained more thermosensitive, even after a 24 hr interval. On the other hand, when cells were exposed to split dose 44 degrees hyperthermia in the presence of MGBG during an interval of 6 hr at 37 degrees, the development of thermotolerance was not inhibited. After the combined treatments of MGBG followed by X-ray irradiation and hyperthermia, cell survival was markedly decreased, as compared with that in the case of X-ray irradiation alone or in combination with hyperthermia.

Hard metal asthma: cross immunological and respiratory reactivity between cobalt and nickel?

Eight asthmatic patients with hard metal asthma due to cobalt underwent bronchial provocation challenge with nickel sulphate. Seven patients developed a fall in FEV1 of 20% or more after inhaling nickel sulphate, four showing an immediate response and three a late response. Eight control subjects, including six asthmatic patients, with no history of hard metal exposure, showed no bronchoconstriction in response to a provocation challenge with nickel sulphate. Specific antibodies to nickel conjugated human serum albumin were present in four of the eight patients with sensitivity to cobalt conjugated human serum albumin but were absent from the serum of 60 unexposed asthmatic patients and 25 exposed symptom free workers. These results suggest that nickel as well as cobalt sensitivity plays a part in hard metal asthma.

[A rare case of allergic granulomatous angitis (Churg Strauss syndrome) with positive anti-glomerular basement membrane (GBM) antibody in serum].

A 33-year-old man with a 6-month history of rhinitis and bronchial asthma was referred to our hospital with polyarthralgia, severe anemia, hypoxemia, mononeuropathy multiplex, and renal insufficiency with hematuria. Marked eosinophilia was observed in his sputum, peripheral blood, and bronchoalveolar lavage fluid (BALF). In addition, his sputum contained many hemosiderin-laden macrophages, indicative of pulmonary hemorrhage. His chest roentgenogram on admission showed diffuse ground grass appearance. High resolution computed tomography (HRCT) demonstrated diffuse high density areas throughout the lung fields and characteristic irregularity and enlargement of the peripheral pulmonary arteries. His general condition rapidly deteriorated, but dramatically improved with oral steroid administration, and his major symptoms disappeared within a few days. Examination of the biopsied lung tissue revealed unequivocal evidence of pulmonary angitis with marked eosinophilic infiltration and perivascular granulomas. Bone marrow biopsy showed hyperplasia of eosinophilic leukocytes in contrast to the low cellularity. Suppression of erythroid hemopoiesis was thought to be the primary cause for his rapidly progressive anemia. Serum anti-GBM antibody titer returned to within the normal range soon after the initiation of steroid therapy.