Protective effect of prophylactic penicillin on splenectomized mice exposed to an aerosolized suspension of type III Streptococcus pneumoniae

Prophylactic penicillin has been recommended for use in asplenic patients and postsplenectomy patients. A laboratory model using aerosolized pneumococci has been devised to test the effectiveness of prophylactic penicillin in a manner analogous to human experience. There is increased mortality, over time, in asplenic mice exposed to aerosolized type III Streptococcus pneumoniae. One hundred twenty-one male Swiss mice (mean weight 26 g) were divided into four groups: splenectomized, sham-operated, splenectomized + penicillin, and sham- operated + penicillin. After 2 wk the four groups were exposed for 30 min to an aerosolized atmosphere of 2.4 x 10(9) colony-forming units of type III S. pneumoniae using a Tri-R model A-42 airborne infection apparatus. Penicillin was given at a daily intramuscular dosage of 40,000 units procaine penicillin G beginning 2 days prior to exposure and continuing through the third day after exposure. The splenectomized and sham-operated mice given penicillin showed significantly lower mortality (p less than 0.001) than mice not given penicillin.     

Multiple myeloma: circulating lymphocytes that express plasma cell antigens

The bone marrow and peripheral blood of 14 patients with multiple myeloma were studied with murine monoclonal antibodies that identify antigens on plasma cells (R1-3 and OKT10). Peripheral blood lymphocytes expressing plasma cell antigens were found in six cases. Five of these cases expressed the same antigens that were present on the plasma cells in the bone marrow. Patients that showed such peripheral blood involvement were found to have a larger tumor burden and higher bone marrow plasma cell proliferative activity. In some patients, antigens normally found at earlier stages of B cell differentiation (B1, B2, and J5) were expressed by peripheral blood lymphocytes and/or bone marrow plasma cells.     

Infrequent alterations of the RAR alpha gene in acute myelogenous leukemias, retinoic acid-resistant acute promyelocytic leukemias, myelodysplastic syndromes, and cell lines

Retinoids are important regulators of cell growth and differentiation in vitro and in vivo and they exert their biologic activities by binding to nuclear retinoic acid receptors (RARs; alpha, beta, and gamma) and retinoid X receptors (RXRs; alpha, beta, and gamma). All- trans retinoic acid (RA) induces complete remission in patients with acute promyelocytic leukemia (APL) presumably by binding directly to RAR alpha of APL cells. Leukemic blasts from APL patients initially responsive to RA can become resistant to the agent. HL-60 myeloblasts cultured with RA have developed mutations of the ligand-binding region of RAR alpha and have become resistant to RA. Furthermore, insertion of an RAR alpha with an alteration in the ligand-binding region into normal murine bone marrow cells can result in growth factor-dependent immortalization of the early hematopoietic cells. To determine if alterations of the ligand binding domain of RAR alpha might be involved in several malignant hematologic disorders, the mutational status of this region (exons 7, 8, and 9) was examined in 118 samples that included a variety of cell lines and fresh cells from patients with myelodysplastic syndromes (MDS) and acute myeloid leukemias (AML), including 20 APL patients, 5 of whom were resistant to RA and 1 who was refractory to RA at diagnosis, using polymerase chain reaction-single- strand conformational polymorphism (PCR-SSCP) analysis and DNA sequencing. In addition, 7 of the 20 APLs were studied for alterations of the other coding exons of the gene (exons 2 through 6). No mutations of RAR alpha were detected. Although the sensitivity of PCR-SSCP analysis is less than 100%, these findings suggest that alterations of RAR alpha gene are rare and therefore other mechanisms must be involved in the onset of resistance to retinoids and in the lack of differentiation in disorders of the myeloid lineage.     

Effect of low-dose prednisone (with calcium and calcitriol supplementation) on calcium and bone metabolism in healthy volunteers

The administration of moderate to high doses of corticosteroids is associated with bone loss. This probably results from the uncoupling of bone formation (decreased) and bone resorption (unchanged or increased). We examined the effect of low-dose (10 mg/day) prednisone (LDP) and the possible mitigating effects of calcium and 1.25 (OH)2 vitamin D (calcitriol) on calcium and bone metabolism in eight healthy, young male volunteers. The study consisted of four observation periods: in the first period, LDP was prescribed during 1 week; in the second, third and fourth periods, calcium (500 mg/day), calcitriol (0.5 micrograms b.i.d.) and calcium in combination with calcitriol, respectively, were added to LDP. Bone formation was measured by means of serum osteocalcin, carboxy-terminal propeptide of type 1 procollagen (P1CP) and alkaline phosphatase, bone resorption by means of urinary excretion of calcium, hydroxyproline, (free and total) pyridinoline, (free and total) deoxypyridinoline and serum carboxy-terminal cross- linked telopeptide of type 1 collagen (1CTP). Dietary calcium and sodium intake were maintained at a stable level during the entire study period. Treatment with LDP led to a decrease in osteocalcin, P1CP and alkaline phosphatase (all P < 0.01). Urinary excretion of pyridinolines, hydroxyproline and serum 1CTP did not increase, but remained unchanged or slightly reduced (P < 0.05), depending on the time of measurement and the marker of bone resorption. Parathyroid hormone (PTH) (insignificantly) increased during LDP (+19%) and LDP plus calcium (+14%), but decreased during supplementation with calcitriol (-16%) and calcium/calcitriol (-44%; P < 0.01). Urinary excretion of calcium increased during treatment with LDP and calcitriol (P < 0.05) and calcium/calcitriol (P < 0.05). It is concluded that LDP has a negative effect on bone metabolism, since bone formation decreased while bone resorption remained unchanged or decreased slightly. The increase in PTH during LDP could be prevented by calcitriol combined with calcium supplementation.      

SWCNT suppress inflammatory mediator responses in human lung epithelium in vitro

Single-walled carbon nanotubes have gained enormous popularity due to a variety of potential applications which will ultimately lead to increased human and environmental exposure to these nanoparticles. This study was carried out in order to evaluate the inflammatory response of immortalised and primary human lung epithelial cells (A549 and NHBE) to single-walled carbon nanotube samples (SWCNT). Special focus was placed on the mediating role of lung surfactant on particle toxicity. The toxicity of SWCNT dispersed in cell culture medium was compared to that of nanotubes dispersed in dipalmitoylphosphatidylcholine (DPPC, the main component of lung lining fluid). Exposure was carried out for 6 to 48 h with the latter time-point showing the most significant responses. Moreover, exposure was performed in the presence of the pro-inflammatory stimulus tumour necrosis factor-α (TNF-α) in order to mimic exposure of stimulated cells, as would occur during infection. Endpoints evaluated included cell viability, proliferation and the analysis of inflammatory mediators such as interleukin (IL)-8, IL-6, TNF-α and macrophage chemoattractant protein-1 (MCP-1). Crocidolite asbestos was included as a well characterised, toxic fibre control. The results of this study showed that HiPco SWCNT samples suppress inflammatory responses of A549 and NHBE cells. This was also true for TNF-α stimulated cells. The use of DPPC improved the degree of SWCNT dispersion in A549 medium and in turn, leads to increased particle toxicity, however, it was not shown to modify NHBE cell responses.     

Prednisolone and salbutamol in the hospital treatment of acute asthma

The use of oral prednisolone (2 mg/kg) to treat children admitted to hospital with acute asthma was assessed in a placebo controlled study. Children were further randomised to receive either 0.15 mg/kg salbutamol every 30 minutes for the first three hours of admission, or 5 mg salbutamol every one to four hours as needed. Treatment was double blind and the assessor was unaware of the nebuliser regimen given. Children were examined before and after treatment with salbutamol on arrival and reassessed four hours after admission. Seventy children completed the study. Seventeen (46%) of 37 children receiving prednisolone and six (9%) of 33 receiving placebo were fit for discharge after four hours of treatment. There was no significant difference between the two nebuliser regimens. Clinical parameters indicative of asthma severity were improved in all groups. Between group comparisons at reassessment showed higher peak flows in those receiving prednisolone and nebulisers every 30 minutes but differences were not significant for other parameters. Objective parameters indicating steroid efficacy over placebo were minimal. Despite this, those receiving prednisolone were more readily identifiable as being fit for discharge within four hours of treatment.