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Biomedical subjects

L Richmond

Publications and source records attributed to L Richmond.

15 recordsLinked to original sources
PubMed2005

Lonafarnib reduces the resistance of primitive quiescent CML cells to imatinib mesylate in vitro.

Recent studies indicate that a rare population of primitive quiescent BCR-ABL(+) cells are innately insensitive to imatinib mesylate (IM) and persist after IM therapy of patients with chronic myeloid leukemia (CML). New approaches to the eradication of these cells are therefore likely to be crucial to the development of curative therapies for CML. We have now found that Ara-C, LY294002 (a PI-3 (phosphatidylinositol-3' kinase) kinase inhibitor), 17AAG (a heat-shock protein (HSP)-90 antagonist) and lonafarnib (a farnesyltransfease inhibitor) all enhance the toxicity of IM on K562 cells and on the total CD34(+) leukemic cell population from chronic phase CML patients. However, for quiescent CD34(+) leukemic cells, this was achieved only by concomitant exposure of the cells to lonafarnib. Ara-C or LY294002 alone blocked the proliferation of these cells but did not kill them, and Ara-C, LY294002 or 17AAG in combination with IM enhanced the cytostatic effect of IM but did not prevent the subsequent regrowth of the surviving leukemic cells. These studies demonstrate the importance of in vitro testing of novel agents on the subset of primary leukemic cells most likely to determine long-term treatment outcomes in vivo.

Antigens, CD34↗
PubMed2004

The effect of interstate travel on sleep patterns of elite Australian Rules footballers.

The purpose of the current study was to examine the effect of interstate air travel on the quality and quantity of sleep in elite Australian Rules football players. Ten elite male athletes, who were members of a Western Australian-based Australian Football League (AFL) team, participated in the study. Sleep pattern was assessed by measuring sleep duration (SLD), sleep efficiency (SE), number of wakings (NW) and total wake time after sleep onset (WT) using a wrist-worn actigraph. Subjective sleep quality (SQ) was assessed using a scale of sleep rating. Throughout the 2002 AFL season, measurements were obtained on the night before (N1), the night of (N2) and the night after (N3) home and away games. Baseline measurements were obtained from five consecutive non-game nights. Compared to baseline, SLD on N1 was increased when home and away (by 51 and 105 mins respectively, p<0.05), while all other measures of sleep pattern were unchanged. On N2, SLD was decreased to a similar degree whether home or away (by 68 and 64 mins respectively, p<0.05), while all other measures of sleep pattern were unchanged. By N3 all measures of sleep pattern had returned to baseline values. Relative to baseline, perception of SQ was worst on N2 of a home game. This study has shown that interstate travel by elite AFL players has no adverse effects on sleep pattern on the night before a game.

Adaptation, Physiological↗
PubMed2001

Intraspecific competition in populations of Helix aspersa with different histories of exposure to lead.

A range of invertebrates have become adapted to certain toxic metals, such that, in the presence of the contaminant, some measure of their performance, typically growth or reproduction, is superior to that of an unexposed population. Under such a toxic stress, a population with a history of exposure might outperform a naïve population in competition for limited resources. This study compared the shell growth of laboratory-bred juveniles from six populations of Helix aspersa with different histories of exposure to Pb. In 10 trials using various combinations of two populations, the snails competed for a limited supply of food that contained either no Pb or 500 micrograms/g-1 Pb, for 98 days. Each trial consisted of 10 juveniles, five from each population and was replicated four times. Nearly all of the food provided was consumed quickly after presentation. The total amount of shell growth within each replicate (the sum of the mean growth of the two populations) was highly consistent between trials so that the total amount of shell built was limited by food availability. The presence of Pb in the diet caused no measurable depression of shell growth and exposure history did not appear to confer any competitive advantage or disadvantage in any of the trials. One population consistently grew faster than its competitors in every trial of which it was a part. Shell growth tended to be greater in smaller juveniles. Snail activity is known to be inhibited at high densities and this may have contributed to the lower incremental growth in individuals kept at the higher densities. The competitive advantage enjoyed by one population may be primarily determined by their activity or perhaps their Ca metabolism.

Adaptation, Physiological↗
PubMed2000

Serving street-dwelling individuals with psychiatric disabilities: outcomes of a psychiatric rehabilitation clinical trial.

OBJECTIVES: This study tested a psychiatric rehabilitation approach for organizing and delivering services to street-dwelling persons with severe mental illness. METHODS: Street-dwelling persons with severe mental illness were randomly assigned to the experimental program (called Choices) or to standard treatment in New York City. We assessed study participants at baseline and at 6-month intervals over 24 months, using measures of service use, quality of life, health, mental health, and social psychological status. The average deviation from baseline summary statistic was employed to assess change. RESULTS: Compared with persons in standard treatment (n = 77), members of the experimental group (n = 91) were more likely to attend a day program (53% vs 27%), had less difficulty in meeting their basic needs, spent less time on the streets (55% vs 28% reduction), and spent more time in community housing (21% vs 9% increase). They showed greater improvement in life satisfaction and experienced a greater reduction in psychiatric symptoms. CONCLUSIONS: With an appropriate service model, it is possible to engage disaffiliated populations, expand their use of human services, and improve their housing conditions, quality of life, and mental health status.

Adult↗
PubMed1998

Variation in the mineral composition of eggs of the snail, Helix aspersa between populations exposed to different levels of metal contamination.

The eggs of terrestrial gastropods represent a major investment of resources by the parent, not least in the provision of essential metals. In this experiment 11 populations of Helix aspersa were collected from habitats with different histories of lead exposure and allowed to reproduce in the laboratory. After 4 months on a low metal diet, five four-egg samples were taken from a single clutch of each population and analysed for their metal content. Within-clutch and between population variation in the eggs were measured. No Pb or Cd was detected in any of the eggs. Both trace and essential metals show considerable variation between eggs within the same clutch. Cu levels were consistent across populations while egg Zn was closely correlated with soil Zn. Median Ca and Mg levels show little relation to soil concentrations. However, Ca provision declines with soil Pb across the populations. While the metal content of the eggs appears to be closely regulated, an interaction between Pb and Ca in the parental tissues may mediate the supply of Ca to the eggs.

Journal Article↗
PubMed1997

CD34 positive PBPC expanded ex vivo may not provide durable engraftment following myeloablative chemoradiotherapy regimens.

We have previously demonstrated that CD34+ cells, selected from peripheral blood progenitor cells (PBPC), can be expanded in ex vivo culture and can be infused in tandem with unmanipulated PBPC with little or no toxicity. In this study, four patients (two non-Hodgkin's lymphoma (NHL), two multiple myeloma (MM)) received myeloablative conditioning prior to stem cell rescue using ex vivo expanded cells alone. The two patients with NHL received cyclophosphamide and total body irradiation (CY/TBI) and the two patients with MM, busulphan and melphalan (Bu/M). One case received an inadequate CFU-GM dose, despite expansion, and in one case the expanded cells were contaminated. No definitive conclusions may therefore be drawn concerning engraftment in these two cases. However, the other two cases received high doses of committed progenitors. Following infusion of the expanded material, all four patients failed to show sustained neutrophil engraftment and none showed evidence of platelet engraftment. Back-up, unmanipulated PBPC were therefore infused on days 14, 34, 32 and 28 and subsequently all four cases achieved satisfactory engraftment of both neutrophils and platelets. In conclusion, we feel that, CD34+ cells, expanded ex vivo using the conditions described in this report, may not provide durable engraftment following fully myeloablative conditioning.

Adult↗
PubMed1997

Efficacy of oral irinotecan against neuroblastoma xenografts.

The efficacy of the topoisomerase I inhibitor, 7-ethyl-10-(4-[1-piperidino]-1-piperidino)-carbonyloxy-camptotheci n (irinotecan, CPT-11), administered by oral gavage has been examined against a panel of six independently derived neuroblastoma xenografts. Irinotecan was administered either daily for 5 days on 12 consecutive weeks ¿(d x 5)12¿ or for 5 days on two consecutive weeks repeated every 21 days for 4 cycles ¿[(d x 5)2]4¿. Given on the (d x 5)12 schedule the maximum tolerated dose (MTD) was 50 mg/kg. For intermittent scheduling ¿[(d x 5)2]4¿, the MTD was 75 mg/kg, resulting in the same total dose being administered (3 g/kg) over the period of treatment. At the MTD for the 12 consecutive week schedule there were two of 42 toxicity related deaths, whereas intermittent scheduling at the MTD resulted in none of 42 deaths. The intermittent schedule ¿[(d x 5)2]4¿ was less toxic than therapy given (d x 5)12, as at the end of treatment mice weighed 92 +/- 4% (SD; n = 6 experiments) and 81 +/- 4% (SD; n = 6 experiments) of their body weight at the start of therapy, respectively. The latter schedule was associated with loose feces starting around week 8 of therapy, broken teeth and a high incidence of swelling of the orbital conjunctiva that developed late in the course of therapy. Given (d x 5)12, irinotecan caused complete regressions of all six neuroblastoma xenograft lines. Because mice tolerate significantly greater systemic exposure to SN-38 lactone than do patients (as determined by plasma AUC at the respective MTD), we evaluated the intermittent schedule of administration, reducing the dose/administration to determine the lowest dose levels that produced objective regressions of these neuroblastoma xenografts and determined the daily systemic exposure associated with these dose levels. In four lines examined objective responses were obtained at dose levels of 12.5 or 6.25 mg/kg. The daily plasma AUC exposures associated with minimum dose achieving response in NB1691 (12.5 mg/kg), NB1643 (6.25 mg/kg) and NBEB (12.5 mg/kg) for irinotecan lactone were 219, 152 and 653 ng-h/ml, respectively; and for SN-38 lactone were 704, 418 and 987 ng-h/ml, respectively. These results indicate that childhood neuroblastoma xenografts are highly sensitive to irinotecan given by oral administration and therapeutic activity is similar to i.v. irinotecan administered on similar schedules.

Administration, Oral↗
PubMed1996

CD34-positive cells isolated from cryopreserved peripheral-blood progenitor cells can be expanded ex vivo and used for transplantation with little or no toxicity.

PURPOSE: The objectives of this phase I study were to assess the feasibility of using cryopreserved peripheral-blood progenitor cells (PBPC) for large-scale CD34 selection and subsequent expansion, and the safety of their use for reinfusion following chemoradiotherapy. PATIENTS AND METHODS: For 10 patients with nonmyeloid malignancy, an aliquot from a PBPC harvest was recovered from liquid nitrogen, and CD34 selected using the Isolex system (Baxter Healthcare, Newbury, United Kingdom) and expanded for 8 days ex vivo in a medium free of animal proteins but supplemented with autologous serum, stemcell factor (SCF), interleukin-1 beta (IL-1 beta), IL-3, IL-6, and erythropoietin. RESULTS: The mean increase for cell number was 21-fold, for colony-forming units-granulocyte/macrophage (CFU-GM) 139-fold, and for burst-forming units-erythroid (BFU-E) 114-fold. The expanded cells were reinfused in tandem with unmanipulated material (> or = 25 x 10(4) CFU-GM/kg). The patients did not experience any adverse effects immediately on cell infusion or within 48 hours. The 10 index patients were compared with 10 historical controls for parameters of myelosuppressive morbidity. In this small study, there were no differences in either neutrophil or platelet recovery between the patients who received expanded cells and historical controls. CONCLUSION: These data demonstrate that CD34 cells can successfully be selected from cryopreserved material, expanded ex vivo on a large scale, and safely reinfused following myeloablative conditioning regimens.

Adolescent↗
PubMed1995

Pregnancy behind bars.

Since the 1960s, the cycle of violence and drug use has mounted and an increasing number of people are being incarcerated. Coincident with this phenomena, we have experienced rising rates of morbidity and mortality among the incarcerated, many of whom suffer from infectious diseases. In fact, the spread of diseases like tuberculosis has been facilitated by the congregate nature of the penal system. As the number of people behind bars has risen, we have seen a disproportionate increase in the number of women incarcerated, most of whom are in their childbearing years. The number of pregnant women in jails and prisons has, in turn, been escalating. Certain prenatal interventions are described and evaluated in the literature, which we review in this article. Experience with the prenatal program in the New York City jail system is described. In general, the authors' position is that as society chooses a social policy of incarceration to address the problems of violence and drug use, there is solid public health reason to design and implement comprehensive prenatal programs in correctional facilities with connections to community-based health services.

Female↗
PubMed1987

Adaptation by an urban population of the snail Helix aspersa to a diet contaminated with lead.

Two populations of the garden snail Helix aspersa, from an urban car park and from a semi-rural site, were fed a diet containing 500 microg g(-1) of Pb as PbSO(4). After 2 days, half of each population was removed to a Pb-free diet and half continued on the dosed food, both for 64 days. The snails from the contaminated site had a significantly lower uptake of Pb compared with those from the rural, uncontaminated site. The car park snails also lost Pb more rapidly from their tissues. A second experiment evaluated the effect of a previous exposure to a high Pb diet on Pb uptake. The results suggest that the differences between the two populations are not due to a physiological adaptation, but rather that the car park snails represent an ecotype adapted to a high Pb diet.

Journal Article↗