Biomedical subjects

B M Daly

Publications and source records attributed to B M Daly.

22 records · Page 2Linked to original sources

PubMedDate not supplied

Antipruritic action of thalidomide.

The effect of thalidomide on itch was studied in 11 patients with chronic pruritus from psoriasis, eczema, nodular prurigo, senile pruritus and primary biliary cirrhosis. Itch, assessed subjectively by the patients on a 10 cm line and measured objectively as nocturnal scratch movement, was decreased by thalidomide 200 mg on the 2 nights it was given. There was no improvement in the underlying disorders and it is concluded that thalidomide is a primary antipruritic agent. The patients all became drowsy and it seems likely that, as with most other antipruritic agents, the antipruritic action of thalidomide results from a central depressant effect. The primary antipruritic effect of thalidomide should now be assessed therapeutically.

Adult↗

PubMedDate not supplied

A hematopoietic stromal lesion associated with fractionated radiotherapy (FxRT): time- and dose-effects.

Earlier, we reported that the local exposure of femoral bone marrow to a clinically-relevant course of fractionated radiotherapy [FxRT; 2.0 Gy (q24h x 5) --> 74 Gy] resulted in the delayed appearance of a stromal lesion which temporally appeared after exposures to a threshold dose of 20 Gy FxRT. To further define this threshold dose, the temporal recovery of blood-forming elements ("cobblestone area" forming colonies; CAFC(7-28d)) and the microenvironmental stroma (long-term bone marrow cultures; LTBMC) of the marrow was examined over a 17-week period following 10 and 30 Gy FxRT. After a subthreshold dose of 10 Gy, each of the 4 CAFC subpopulations were significantly dampened, with recovery initiated within a 6-week interval of 10 Gy of FxRT. Above the threshold dose (30 Gy FxRT), the CAFC subpopulations were again reduced to a level similar to that observed with 10 Gy FxRT. However, after exposures to 30 Gy FxRT, CAFC recovery was significantly well beyond the 6-week interval observed with a 10 Gy Dose of FxRT. Similarly, cell production in LTBMC prepared from marrow exposed to either 10 or 30 Gy FxRT was significantly dampened for at least 3 weeks following the FxRT. Moreover, while cell production in LTBMC derived from marrow exposed to 10 Gy was eventually restored to normal, the dampened cell production observed in LTBMC prepared after 30 Gy FxRT persisted for a period in excess of 17 weeks. Collectively, these observations provide additional support to our earlier observation suggesting that FxRT generates two forms of dose-dependent damage in the marrow: the first an early lesion arising in the blood-forming CAFC subpopulations; the second form, a delayed lesion that involves the persistent expression of a dysfunctional microenvironmental phenotype, appearing to disrupt the normal regulation of hematopoietic stem cell (HSC) proliferation and differentiation of the HSC during the recovery process.

Animals↗

PubMedDate not supplied

Antioxidant enzyme activity in murine hematopoietic bone marrow following treatment with interleukin 1 alpha: influence of tumor.

To determine whether non-hematologic tumors influence the bone marrow's antioxidant enzyme response to the radioprotective cytokine interleukin 1 alpha (IL-1), studies were undertaken using BDF1 and Balb/c mice bearing small, medium or large Lewis lung carcinoma (LLCa) or EMT6 mammary carcinoma tumors, respectively. Results demonstrated that, similar to nontumor-bearing mice, treatment of tumor-bearing animals with IL-1 was associated with a significant increase in marrow MnSOD activity. However, the duration of this elevated activity was reduced as tumor burden increased, and this reduction may have an impact on IL-1's ability to radioprotect tumor bearing animals, especially when tumor burden is large. In addition to cytokine-mediated responses, significant tumor-related influences on the marrow's antioxidant enzyme status were seen. Notably, it was observed that the presence of tumor was correlated with a marked suppression of antioxidant enzyme activity. Surprisingly, however, the pattern of enzyme suppression was found to differ between the two tumor models studied both in temporal onset and in the number of enzymes involved. In conclusion, the data obtained from these studies on tumor-bearing animals demonstrate that there are both cytokine-related and tumor-related influences which can effect the antioxidant enzyme status of the hematopoietic marrow-influences which may have the potential to alter the marrow's ability to tolerate free radical-generating events, both endogenous (i.e inflammation, infection) and exogenous (i.e. radiation, certain chemotherapeutic drugs) in origin.

Animals↗

PubMedDate not supplied

Interleukin 1 alpha (IL-1) and macrophage colony-stimulating factor (M-CSF) accelerate recovery from multiple drug-induced myelosuppression.

Interleukin 1 alpha (IL-1) and macrophage colony-stimulating factor (M-CSF) interact synergistically to enhance the restoration of stem and progenitor subpopulations in murine marrow and, vis-a-vis, to accelerate hematopoietic recovery in 5FU myelosuppressed mice. Similarly, IL-1 is reported to accelerate recovery following myelosuppressive treatment with doxorubicin (AdR), cis-platinum (DDP) and cyclophosphamide (CTx). Studies were carried out in C57Bl/6 mice in order to determine whether IL-1 (+/- M-CSF) intervention was as effective against the myelosuppression experienced following 5FU-based multiple drug combinations. Maximal-tolerated doses (MTD) of AdR (10 mg/kg), DDP (8 mg/kg) or CTx (250 mg/kg) were administered either alone or in combination with 150 mg/kg 5FU. Cytokine intervention (q24 hours x 2) was initiated 24 hours later. Hematopoietic recovery was assessed by measuring the femoral content of the more primitive [IL-1 + IL-3 + M-CSF-responsive] HPP-CFC and the total granulocyte levels in the animals over a ten-day interval following treatment. MTDs of AdR, DDP and CTx, when compared with 5FU, produced only marginal levels of myelosuppression. As a result, cytokine intervention in animals treated with AdR, DDP or CTx resulted in only a modest, transient increase in the HPP-CFC and total granulocyte subpopulations when compared with their effect on 5FU--treated animals. Neither AdR, DDP nor CTx interacted with 5FU to significantly increase the cytotoxic effects of 5FU on the HPP-CFC or granulocyte subpopulations, and both IL-1 and IL-1 + M-CSF effectively stimulated hematopoietic recovery in all animals that received the 5FU--based drug combinations. However, the significant advantage (p < 0.05) achieved by combining IL-1 + M-CSF (vs. IL-1 alone) was only observed in animals that were treated with 5FU and either AdR or DDP. Furthermore, the initial stimulation of HPP-CFC recovery by IL-1 + M-CSF in animals that received DDP + 5FU, when compared with 5FU alone, was subsequently dampened. Although there were subtle, drug-related differences in the temporal response of the more primitive HPP-CFC and granulocyte populations to cytokine therapy, the data from this study demonstrated that abbreviated cytokine interaction can effectively accelerate hematopoietic recovery after combination drug therapy.

Animals↗