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Biomedical subjects

S C Miller

Publications and source records attributed to S C Miller.

At least 37 records · Page 2Linked to original sources
PubMed2002

Extrapulmonary organ distribution of plutonium in healthy workers exposed by chronic inhalation at the Mayak production association.

The systemic distribution of plutonium was determined for "healthy" workers who chronically inhaled plutonium at the radiochemical plants of the Mayak Production Association. The data were obtained by radiochemical analysis of soft tissues and bones samples collected upon autopsy of 120 workers who died from acute coronary diseases and accidents. The soft tissue samples were wet-ashed using nitric acid and hydrogen peroxide. Bone samples were ashed in a muffle furnace at 500 degrees C. Plutonium was extracted on anionite and coprecipitated with bismuth phosphate. The precipitation was blended with ZnS powder, and the alpha-activity was measured by ZnS solid scintillation counting in a low-background alpha radiometer. Twenty-five years after the beginning of inhalation exposures, the average percentage of plutonium in the skeleton and liver was 50% and 42% of systemic burden, respectively. A multivariate regression was used to quantify the effects of exposure time, "transportability" of the various compounds, plutonium body content, and age on systemic plutonium distribution. The early retention of plutonium in the liver is assumed to be greater than that in the skeleton. The initial distribution of plutonium between the liver and the skeleton, immediately after entering the circulatory system, was 50:38%, respectively. With time, the fraction of plutonium found in the liver decreased, while the fraction in the skeleton increased at a rate of 0.5% y(-1) of systemic deposition. Exposure time had a greater effect on the relative retention of plutonium in the main organs when compared to age. The statistical estimates that characterized the relative plutonium distribution were less stable for the liver than for the skeleton, likely due to the slower turnover of skeletal tissues and the retention of plutonium in bone.

Administration, Inhalation↗
PubMed2002

Greatly increased cancellous bone formation with rapid improvements in bone structure in the rat maternal skeleton after lactation.

There is a decrease in cancellous bone mass and strength during lactation but these are partially or completely reconstituted in the postlactational period. The purpose of this study was to determine changes in cancellous bone structure and formation after lactation in established breeder rats. For this, rats were taken at the end of the second pregnancy (Preg-2) and second lactation (Lac-2) and 2, 4, and 6 weeks after weaning. Nulliparous (NP) groups were included for comparisons. Bone structure was measured using morphometric methods and bone dynamics by histomorphometry. Tibial metaphyseal cancellous bone was lost during the first reproductive cycle, as expected, and again depleted during the Lac-2. Bone formation indices were elevated at the end of Lac-2, compared with those at the end of the second pregnancy or in the nulliparous animals. Within 2 weeks after the second weaning, the amount of double-labeled surface (dLS) increased approximately 800%, the mineralizing surface (MS) increased >400% with similar increases in bone formation rates (BFRs), compared with already elevated bone formation measured at the end of Lac-2. From 2 to 4 weeks after lactation, there were commensurate increases in cancellous bone mass and structural indices with essentially complete restoration of cancellous bone volume and structure compared with that measured at the end of Preg-2. The results show rapid and substantial increases in bone formation with reconstitution of cancellous bone mass and structure after lactation in rats. The skeletal changes that occur during the postlactational period may serve to prepare and protect the maternal skeleton for subsequent reproductive cycles.

Animals↗
PubMed2001

TNF-alpha further augments natural killer cells when co-administered with an interferon inducer to irradiated, leukemic, bone-marrow-transplanted mice.

PURPOSE: We have recently demonstrated that the interferon inducer Poly I:C significantly augments both natural killer (NK) cell numbers and the life span of leukemic, irradiated mice given syngeneic bone marrow transplants (SBMT). The cytokine tumor necrosis factor-alpha (TNF-alpha) also stimulates NK cells directly through receptor-ligand mechanisms. We have combined in the present study the NK-enhancing properties of IFN (Poly I:C-induced) and TNF-alpha by giving Poly I:C to leukemic mice for 8 days after irradiation and SBMT, concomitant with TNF-alpha during the first 4 days immediately after SBMT. All mice were sampled at day 9 following irradiation, transplant, and treatment. METHODS: NK cells were identified and quantified by immunoperosidase labeling methods combined with a hematologic staining technique. RESULTS: The data reveal that TNF-alpha, added to the Poly I:C administration protocol, significantly boosted NK cell numbers 2.4-fold over that achieved by Poly I:C alone. CONCLUSIONS: Since the role of NK cells in the immediate post-transplant period is (a) to destroy residual tumor cells, and (b) to produce hemopoiesis-driving cytokines, it appears that two NK cell stimulants are better than one, at least in the crucial, early post-transplant period.

Animals↗
PubMed2001

Hospice enrollment and hospitalization of dying nursing home patients.

PURPOSE: This study's purpose was to evaluate whether Medicare hospice care provided in nursing homes is associated with lower hospitalization rates. SUBJECTS AND METHODS: This retrospective cohort study included nursing home residents in five states who enrolled in hospice between 1992 and 1996 (n = 9202), and who died before 1998. For each hospice patient, 3 nonhospice residents (2 in 106 instances) were chosen (n = 27,500). Medicare claims identified hospice enrollment and acute care hospitalizations. RESULTS: Twenty-four percent of hospice and 44% of nonhospice residents were hospitalized in the last 30 days of life. Adjusting for confounders, hospice patients were less likely than nonhospice residents to be hospitalized (odds ratio 0.43; 95% confidence interval [CI]: 0.39 to 0.46). Considering all of nonhospice residents who died (n = 226,469), those in facilities with no hospice had a 47% hospitalization rate, whereas rates were 41% in facilities with low hospice use and 39% in facilities with moderate hospice use (5%+ of patients in hospice). Hospitalization was less likely for nonhospice residents in facilities with low hospice use (odds ratio 0.82; 95% CI: 0.80 to 0.84) and moderate hospice use (odds ratio 0.71; 95% CI: 0.69 to 0.74), compared with those in facilities with no hospice. CONCLUSIONS: When integrated into the nursing home care processes, hospice care is associated with less hospitalization for Medicare hospice patients. Additionally, possibly through diffusion of palliative care philosophy and practices, nonhospice residents who died in nursing homes having a hospice presence had lower rates of end-of-life hospitalizations.

Aged↗
PubMed2001

Using point-of-care CD34 enumeration to optimize PBSC collection conditions.

BACKGROUND: A PBSC graft containing 4-5 x 10(6) CD34(+) cells/kg is considered optimal in terms of durable engraftment. Tracking CD34 kinetics via point-of-care testing during PBSC mobilization could determine which (and when) patients will yield an optimal product. We evaluated whether microvolume fluorimetry (MVF) would be useful in optimizing PBSC mobilization/harvest and if it will shorten our standard 6 h collection. METHODS: Absolute CD34 values were obtained using the IMAGN 2000 and STELLer CD34 assay (50 microL sample volume). Peripheral blood (PB) CD34 values from 30 patients undergoing PBSC mobilization were used to generate a PB CD34-based algorithm that would predict collection day/duration of apheresis. The algorithm was then used prospectively to collect PBSC products on 50 hematologic malignancy (HM) patients. RESULTS: Using the algorithm, patients were assigned to either a 6 (11-20 CD34/microL), 4 (21-49 CD34/microL) or 2 (> or = 50 CD34/microL) h collection. Patients with a CD34 value < or = 10/microL were re-tested. All patients (n = 43) predicted to mobilize reached the optimal CD34 (4-5 x 10(6)/kg) value with 1.0 apheresis procedure; seven patients had < or = 10/microL (nonmobilizers). The majority (75%) had apheresis charges decreased by 33-66%; 47% only required a 2 h procedure and 28% required 4 h. All patients demonstrated rapid trilineage engraftment. DISCUSSION: Absolute PB CD34 measurement using MVF offers a rapid and reliable approach to obtaining optimal PBSC products with minimal technical expertise. Although not a replacement for conventional flow cytometry, it meets the requirements for a point-of-care procedure.

Algorithms↗
PubMed2001

Echinacea purpurea and melatonin augment natural-killer cells in leukemic mice and prolong life span.

OBJECTIVE: We recently showed that daily dietary administration of Echinacea purpurea root extract to normal mice for as little as 1 week resulted in significant elevations of natural-killer (NK) cells (immune cells that are cytolytic to virus-containing cells and many tumor cells). Such boosting of this fundamental immune cell population suggests a prophylactic role for this herb in normal animals. Based on this evidence, our goal in the present work was to assess the role of dietary administration of this herbal extract to mice bearing leukemia, a type of tumor well known to be a target for NK cells. DESIGN: A commercially available root extract of E. purpurea, which we have already shown to be highly effective in mice, was administered daily for 50 days from the onset of leukemia (day 0). Control leukemic mice received no extract. Other leukemic mice received the NK-enhancing neurohormone, melatonin, administered precisely as above. In all treatment and control categories, some mice were sampled at 9 days after tumor onset, others were sampled at 3 months, and still others were left to assess treatment effect on life span. RESULTS: At 9 days (intermediate stage leukemia; death beginning by day 17-18), E. purpurea-treated mice had a 2.5-fold increase in the absolute numbers of NK cells in their spleens. By 3 months after leukemia onset, E. purpurea-treated mice still had 2-3 times the normal numbers of NK cells in their spleens. No leukemic, untreated (control) mice remained alive at 3 months, hence the comparison with normal animals. Moreover, at 3 months post-tumor onset, all the major hemopoietic and immune cell lineages in their bone marrow birth site, were recorded at normal numbers, in E. purpurea-consuming, leukemic mice. The survival advantage provided by administering these leukemic mice with E. purpurea was highly significant versus untreated, leukemic mice when analyzed by Kaplan-Meier survival statistics. CONCLUSION: The present study has provided the first systematic analysis, under controlled laboratory conditions, of the effect(s) of the botanical, E. purpurea, in vivo, in leukemic hosts. The profoundly positive effects of this herb in disease abatement observed in this study suggest the therapeutic potential of E. purpurea, at least with respect to leukemia, if not other tumors as well.

Animals↗
PubMed2001

Cancellous and cortical bone mechanical properties and tissue dynamics during pregnancy, lactation, and postlactation in the rat.

There are substantial changes in maternal skeletal dynamics during pregnancy, lactation, and after lactation. The purpose of this study was to correlate changes in cortical and cancellous bone mass, structure, and dynamics with mechanical properties during and after the first reproductive cycle in rats. Rats were mated and groups were taken at parturition, end of lactation and 8 wk after weaning, and were compared with age-matched, nulliparous controls. Measurements were taken on femoral cortical bone and lumbar vertebral body cancellous bone. At the end of pregnancy, there was an increase in cortical periosteal bone formation and an increase in cortical volume, but a suppression of turnover in cancellous bone with no change in cancellous or cortical mechanical properties. Lactation was associated with a decrease in cortical and cancellous bone strength with a decrease in bone volume, but an increase in turnover on cancellous and endocortical surfaces. After lactation, there was a partial or full restoration of mechanical properties. This study demonstrates substantial changes in bone mechanics that correlate with changes in bone structure and dynamics during the first reproductive cycle in rats. The greatest changes were observed during the lactation period with partial or full recovery in the postlactational period.

Animals↗
PubMed2001

Does longevity in beagles injected with bone-seeking radionuclides depend upon radiation dose in the absence of known radiation effects?

Regression analyses of longevity as a function of skeletal radiation dose among groups of beagles injected with 226Ra, 228Ra, 228Th, 241Am, 90Sr or monomeric 239Pu suggested that at low doses and dose-rates (those at which induced effects are low), age at death seems to be independent of dose when animals dying with specific radiation effects were excluded, although longevity does appear to be a function of dose when animals dying with established radiation effects and at all doses were included. We conclude tentatively that, for mammals receiving skeletal dose from bone-seeking radionuclides at low doses and low dose-rates, longevity may not be dependent upon skeletal radiation dose in the absence of radiation-induced malignancies or other radiation effects.

Americium↗
PubMed2001

Review of 239Pu and 226Ra effects in beagles.

A long term biological study has been completed that was designed to assess the predicted effects in humans of internally deposited 239Pu by comparison with 226Ra in beagles. Herein we summarize for the first time results of several previous reports about the effects of these two radionuclides in our beagles in an attempt to elucidate what has been learned since the beginning of the study in the early 1950's. Perhaps the most important finding was that bone surface-seeking plutonium is more toxic at equal mean skeletal radiation doses (<3 Gy for 239Pu, <20 Gy for 226Ra) than bone volume-seeking radium for the induction of skeletal malignancy by about a factor of 16 for a single intravenous injection of monomeric 239Pu. In addition, ancillary studies have shown that when plutonium transfers continuously onto bone surfaces from a depot of particulate 239Pu in phagocytic cells, its relative toxicity per Gy average skeletal dose is enhanced by about a factor of 2. Juvenile animals or dogs injected as mature adults were only about half as sensitive for equal mean skeletal doses as dogs injected as young adults. Male and female dogs were about equally sensitive to radiation of the skeleton by either radionuclide. Findings about radiation-induced fractures are summarized as well as data on the induction of soft-tissue malignancies by 239Pu or 226Ra. Natural survival was not affected at the lower dosage levels of either 226Ra or 239Pu as compared with control dogs given no radioactivity, but the survival of animals at higher levels was reduced. No additional life-shortening effects beyond those attributable to occurrence of radiation-induced malignancies or other radiation-induced effects were suggested by analysis of data for low dosage levels.

Animals↗
PubMed2001

Swim-trained rats have greater bone mass, density, strength, and dynamics.

Weight-bearing exercise is traditionally recommended for improving bone health in postmenopausal women. Effects of swim exercise were studied as an alternative to weight-bearing exercise in ovariectomized rats. Rats in a swim group (Sw, n = 8) swam for 12 wk, 5 days/wk for 60 min per session. A control group (Con, n = 9) engaged in no structured exercise. Femurs were analyzed for bone mineral density and for bone mineral content by dual energy X-ray absorptiometry, biomechanical properties by three-point bending (Instron), and bone structure and formation by histomorphometry. Food intake did not differ among groups. Final body weights were significantly lower in Sw compared with Con (P < 0.05). Swimmers had significantly greater femoral shaft bone mineral density and content (P < 0.05) compared with Con. Femurs of the Sw group had greater mechanical properties (P < 0.05) compared with Con. Histomorphometric data were significantly better in the Sw group compared with Con after the 12-wk intervention (P < 0.05). In conclusion, data from this study demonstrate some beneficial effects of swim exercise on bone structure, turnover, and strength.

Absorptiometry, Photon↗
PubMed2001

The emergence of Medicare hospice care in US nursing homes.

Although Medicare-financed hospice care has been provided in nursing homes in the USA for over 10 years, very little is known regarding the use of this government health care benefit in nursing homes. Using resident assessment data and hospice and inpatient Medicare claim data from five US states, we were able to identify and describe nursing home residents receiving hospice care between 1992 and 1996, and their hospice utilization patterns. Six per cent of all dying nursing home residents received hospice care at some point in time and, in 1996, an estimated 24% of all Medicare hospice patients in the five study states received hospice while in a nursing home. Of those residents beginning hospice care after nursing home admission, 48% were 85 years or older, 70% were female, 94% were white, 76% were unmarried and 62% had a non-cancer principal diagnosis. The average length of stay in the hospice programme for residents receiving hospice care while in the nursing home was 90.6 days, the median 35 and the mode 2. Hospice care in US nursing homes is a prevalent model of care that appears further to extend the Medicare hospice benefit to older adults who are female and to those with non-cancer diagnoses. Lengths of stay in the programme are similar to those observed in the community and the average length of stay is substantially shorter than previously estimated by an influential government study.

Aged↗
PubMed2001

Complicated dual diagnosis: a case for physician involvement in addictions treatment.

Despite the high prevalence of substance use disorders, the prevention and treatment of such illnesses seem to receive little attention during physician training. This provides cause for concern, as physician involvement in addiction treatment has been relatively sparse. We present the case of a patient whose successful treatment likely relied upon her physicians' intensive training in each of the biological, psychological, and social aspects of her clinical presentation. The case illustrates the need for added emphasis on the assessment and treatment of addictive disorders during medical training, and for more active physician involvement in addictions treatment.

Adult↗
PubMed2001

Deleterious effects of Echinacea purpurea and melatonin on myeloid cells in mouse spleen and bone marrow.

The neurohormone, melatonin, a product of the pineal gland, is a potent immune cell stimulant. Phytochemicals contained in root extracts of the plant species Echinacea purpurea are also potent as immune cell stimulants. Both agents are potent stimulants of T, B, and/or natural killer cells, but little is known of their effect on other hemopoietic cells, specifically granular leukocytes, also participants in a wide variety of disease defense processes. Given their current popularity and availability for amelioration of a) jet lag and sleep disorders (melatonin) and b) virus-mediated respiratory infections (E. purpurea), we investigated the effects of these agents on granular leukocytes and their precursors, myeloid cells. Mice received these agents daily for 7 or 14 days via the diet, thus mimicking human administration, after which spleens and bone marrow were removed and assessed for mature, differentiated granulocytes and their myeloid progenitors. The influence of these agents was directly related to the stage of cell maturity. Administration of both agents together resulted in significantly elevated levels of myeloid progenitor cells in both bone marrow and spleen and significantly reduced levels of mature, functional granulocyte progeny in both organs, suggesting a) increased precursor proliferation, b) antiapoptosis among the progenitors, and/or c) inhibition of precursor maturation-the latter readily explaining the paucity of mature granulocyte progeny. In conclusion, individual administration of either the herbal derivative and melatonin was either without effect (E. purpurea) or even advantageous (melatonin) to cells of this lineage, but when administered together, these agents significantly perturbed myelopoiesis.

Animals↗
PubMed2001

Spaceflight alters bone mechanics and modeling drifts in growing rats.

BACKGROUND: Alterations in bone metabolism may be a particularly serious consequence of spaceflight and a major obstacle to long-term space exploration. The effects of spaceflight on bone mechanics are unclear. This study examined the effects of spaceflight on bone mechanics in a growing rat model during a 17-d mission aboard the space shuttle (STS-78). METHODS: There were 18 rats that were divided into 3 experimental groups: flight rats (n = 6), ground-based control rats housed in an animal enclosure module (AEM, n = 6), and ground-based control rats housed in standard vivarium caging (n = 6). At the conclusion of the mission, rat femurs were tested in three-point bending followed by static and dynamic bone histomorphometry. RESULTS: Maximum stress was unaffected by spaceflight, but flexural rigidity was significantly decreased in flight animals. Much of the decrease appeared to be the result of decreases in tissue properties (elastic modulus) rather than structural changes within the bone. No significant differences in cortical bone mass or geometry were observed. In contrast, endocortical resorption was significantly decreased in flight rats accompanied by a nonsignificant decrease in periosteal bone formation, suggesting alterations in bone modeling drifts during spaceflight. For nearly all measured indices, ground-based AEM rats displayed values intermediate to flight and ground-based vivarium rats. CONCLUSIONS: Spaceflight can impair tissue properties in femoral cortical bone during growth without significant decreases in bone mass or geometry.

Adaptation, Physiological↗
PubMed2001

Skeletal adaptations during mammalian reproduction.

Remarkable changes occur in the mammalian skeleton prior to, during and after the reproductive cycle. Skeletal changes occur with ovarian maturation and initiation of menses and estrus in adolescence, which may result in a greater accumulation of skeletal mineral in the female vs the male skeleton. There is also some evidence to suggest an excess skeletal mass in young female experimental animals. In early pregnancy, growth, modeling and perhaps suppressed remodeling promote the accumulation of calcium. Some changes may also occur with the transition from pituitary to placental control of the pregnancy. In later pregnancy, an increase in bone turnover appears to coincide with fetal skeletal mineralization. Rapid and important changes occur in the skeleton and mineral metabolism in the transition from pregnancy to lactation as the mammary gland rather than the uterus draws on the maternal calcium stores. Lactational demands are met at least partially by a temporary demineralization of the skeleton, which is associated with increased bone modeling and remodeling. Endochondral growth almost ceases during lactation, but envelope-specific bone modeling and remodeling are greatly increased. This is generally associated with a loss of skeletal mass and density, more apparent at sites with less of a mechanical role (e.g. central metaphysis regions and the endocortical envelope). The post-lactational period is profoundly anabolic with substantial increases in bone formation, but blunted resorption at almost all skeletal envelopes. Skeletal mass is increased during this period and it is associated with improved skeletal mechanical properties. There are several important observations. 1) The nulliparous animal appears to have an excess skeletal mass to perhaps compensate for maternal metabolic inefficiency of the first reproductive cycle. 2) Changes in growth, modeling and remodeling occur at different times and at different skeletal envelopes during the reproductive cycle. These site-specific, temporal changes appear to be adaptations that facilitate the use of skeletal mineral while preserving mechanical competence. 3) After the first reproductive cycle, modeling and remodeling optimize the existing skeletal mass into a structure that better accommodates the prevailing mechanical environment. 4) The post-lactational period is profoundly anabolic and may provide new strategies for preservation of skeletal mass when reproductive capacity ceases.

Journal Article↗
PubMed2000

Exogenous melatonin: quantitative enhancement in vivo of cells mediating non-specific immunity.

Melatonin (MLT), a biogenic indoleamine and neuromodulator produced by the pineal gland, is known to activate T helper cells by means of direct binding to melatonin receptors on both Th1 and Th2 cells. The present in vivo study aimed to investigate the effect of exogenously administered MLT on the hemopoietic and immune cell populations of the bone marrow and spleen in healthy, young adult male mice at two distinct MLT exposure intervals. The neurohormone, administered daily through the diet (7-14 days), was homogenized into finely ground chow. Control mice received ground chow without MLT. The results revealed cell lineage-specific, quantitative, MLT exposure-time-dependent changes in both the bone marrow and spleen. NK cells and monocytes (both components of the non-specific immune system functioning as the first line of defense against neoplasia and virus infected cells) were significantly increased in the bone marrow by both 7 and 14 days of dietary melatonin. The quantitative increment in these two cell populations, in the organ of their production, i.e. the bone marrow, indicates that new cell proliferation/production may have been stimulated by MLT. In the spleen, as in the bone marrow, NK cell levels remained significantly elevated at both 7 and 14 days after melatonin exposure. However, the number of monocytes in the spleen did not maintain, at day 14 of MLT exposure, the high levels observed after 7 days of MLT, in spite of their sustained, high numbers at 14 days in the bone marrow. This suggests that the progeny of the apparently increased monocyte production in the bone marrow (elevated absolute numbers therein), had localized in anatomical sites (other than the spleen) also common to these cells. Thus, the selective, positive influences of in vivo administered, exogenous melatonin on cells mediating non-specific immunity suggests a plausible mechanism for numerous claims that it is responsible for tumor amelioration in patients.

Adjuvants, Immunologic↗