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Biomedical subjects

A M Miller

Publications and source records attributed to A M Miller.

At least 19 recordsLinked to original sources

Resolution of chronic idiopathic thrombocytopenia purpura following syngeneic peripheral blood progenitor transplant.

Idiopathic thrombocytopenia purpura (ITP) is an acquired disease of children and adults characterized by a low platelet count, an essentially normal bone marrow, and absence of evidence for other disease. We report the use of syngeneic peripheral blood progenitor transplantation (PBPT) in a 19-year-old male with chronic refractory ITP since the age of 5. Engraftment was successful and has resulted in resolution of his disease. We conclude that syngeneic PBPT is a potentially curative option for refractory ITP.

Adult↗

Validation of a technique to measure leukocyte adhesion to arterial segments: effects of drug treatments.

Adhesion and transmigration of leukocytes into arterial walls occurs after vascular injury and may play a role in the development of atherosclerosis and restenosis. This protocol presents a simple, rapid method for quantifying leukocyte adhesion to artery segments ex vivo. The procedure involves isolating leukocytes from rabbit whole blood and labelling with the gamma-emitting isotope 51Cr. Labelled leukocytes are added to open rings of subclavian artery taken from the same rabbit. After gamma counting, percentage leukocyte adhesion can be calculated with reference to a sample containing a quantity of labelled leukocytes equivalent to that which was added to the artery. Leukocyte adhesion was increased by L-NAME, thrombin and increasing incubation time and decreased by low temperatures. In addition, leukocyte adhesion was found to be increased following a vascular stretch injury performed in vitro. This protocol offers a number of advantages: the rapidity of the leukocyte isolation and labelling; the small quantity of leukocytes required; the ability to use autologous leukocytes; the applicability to whole arteries and arteries injured in vitro or in vivo, allowing the effects of vascular injury on leukocyte adhesion to be studied.

Animals↗

Inhibition by leukocyte depletion of neointima formation after balloon angioplasty in a rabbit model of restenosis.

OBJECTIVE: The aim of the current study was to examine neointima formation in balloon injured left subclavian artery of rabbits subjected to two different methods of leukocyte depletion at the time of injury. METHODS: Angioplasty of the left subclavian artery was performed in leukopenic male New Zealand White rabbits. Depletion of circulating leukocytes was induced by either mustine hydrochloride or an antibody against leukocyte common antigen (anti-LCA) before angioplasty. Left and right subclavian arteries were removed 28 days after injury for morphological analysis and measurement of neointimal size. At the same time, leukocytes were isolated from autologous rabbit blood for 51Cr-labelling for assessment of leukocyte adhesion to injured and non-injured artery segments. RESULTS: Leukopenia decreased neointima formation in injured arteries (neointimal area was 0.09+/-0.03 mm(2) in mustine-treated arteries, n=8, vs. 0.56+/-0.07 mm(2) in control arteries, n=7; P<0.001 and 0.07+/-0.01 mm(2) in anti-LCA treated arteries, n=9, vs. 0.22+/-0.04 mm(2) in non immune serum-treated arteries, n=9; P<0.001). Adventitial fibrosis was also significantly (P<0.05) decreased by both leukopenic interventions. Neither medial nor adventitial area was modified in any of the groups. No differences in leukocyte adhesion were observed between injured and non-injured arteries in any of the experimental groups at the 28 day time point. CONCLUSION: These results suggest that leukocytes play a major role in the development of two of the major characteristics of the response to balloon injury, namely formation of neointima and adventitial fibrosis, that currently limit the success of clinical angioplasty. Elucidation of the fine mechanisms involved in leukocyte-mediated injury may lead to the discovery of novel therapeutic targets for the prevention of restenosis.

Angioplasty, Balloon↗

Autotransplants for Hodgkin's disease in first relapse or second remission: a report from the autologous blood and marrow transplant registry (ABMTR).

Although patients with relapsed Hodgkin's disease have a poor prognosis with conventional therapies, high-dose chemotherapy and autologous hematopoietic stem cell transplantation (autotransplantation) may provide long-term progression-free survival. We reviewed data from the Autologous Blood and Marrow Transplant Registry (ABMTR) to determine relapse, disease-free survival, overall survival, and prognostic factors in this group of patients. Detailed records from the ABMTR on 414 patients with Hodgkin's disease in first relapse (n = 295) or second complete remission (CR) (n = 119) receiving an autotransplant from 1989 to 1995 were reviewed. Median age was 29 (range, 7-64) years. Median time from diagnosis to relapse was 18 (range, 6-219) months; median time from relapse to transplant was 5 (range, <1-215) months. Most patients received high-dose chemotherapy without total body irradiation for conditioning (n = 370). The most frequently used high-dose regimen was cyclophosphamide, BCNU, VP-16 (CBV) (n = 240). The graft consisted of bone marrow (n = 246), blood stem cells (n = 112), or both (n = 56). Median follow-up was 46 (range, 5-96) months. One hundred-day mortality (95% confidence interval) was 7 (5-9)%. One hundred and sixty-five of 295 patients (56%) transplanted in relapse achieved CR after autotransplantation. Of these, 61 (37%) recurred. Twenty-four of 119 patients (20%) transplanted in CR recurred. The probability of disease-free survival at 3 years was 46 (40-52)% for transplants in first relapse and 64 (53-72)% for those in second remission (P < 0.001). Overall survival at 3 years was 58 (52-64)% after transplantation in first relapse and 75 (66-83)% after transplantation in second CR (P < 0.001). In multivariate analysis, Karnofsky performance score <90% at transplant, abnormal serum LDH at transplant, and chemotherapy resistance were adverse prognostic factors for outcome. Progression of Hodgkin's disease accounted for 69% of all deaths. Autotransplantation should be considered for patients with Hodgkin's disease in first relapse or second remission. Future investigations should focus on strategies designed to decrease relapse after autotransplantation, particularly in patients at high risk for relapse.

Adolescent↗

Inflammation as a key event in the development of neointima following vascular balloon injury.

1. The present review discusses the current evidence to implicate leucocytes as key players in the development of neointima in arteries that have been subjected to balloon angioplasty injury. 2. There is substantial clinical evidence that leucocytes are activated after angioplasty, as determined by increased plasma levels of both leucocyte granulation products and soluble leucocyte and endothelial cell adhesion molecules. 3. Experimental evidence to implicate leucocytes in neointimal formation comes from studies that demonstrate leucocyte accumulation occurs within the vascular wall soon after injury and that induction of leukopenia prevents neointimal formation. 4. The evidence implicating specific adhesion molecules and cytokines in the key events leading to neointimal formation is discussed.

Angioplasty, Balloon↗

Rapid response of severe refractory metastatic Crohn's disease to infliximab.

A case is described of a middle-aged female who developed an aggressive form of biopsy-proven metastatic Crohn's disease involving the inguinal, perineal and submammary areas. Her condition had been unresponsive to topical and systemic corticosteroids, antibiotics, immunosuppressives, and repeated surgical debridement. Administration of infliximab resulted in a rapid clinical response with subjective improvements in pain and general well-being, and an objective decline in exudate, erythema and size of the lesions. Infliximab may be a suitable therapeutic option in patients with metastatic Crohn's disease.

Antibodies, Monoclonal↗

Measuring adherence to a women's walking program.

The purpose of this study is to demonstrate the use of a self-report exercise log and a heart-rate monitor in the measurement of adherence to the dimensions of an exercise prescription and to propose an alternative way to define adherence to a 24-week home-based women's walking program, which reflects the dynamic process of behavior change. Adherence was measured with exercise logs, Polar Vantage XL Heart-Rate Monitors, and pre- to postintervention change in VO2 max. Of the dimensions of the exercise prescription, frequency of walks documented by both the heart-rate monitor and the exercise log had a higher correlation than duration and intensity of walking, with change in VO2 max suggesting that frequency was potentially the most predictive adherence measure. Examination of the total number of walks and the number and sequence of weeks without walks over the 24-week intervention revealed dynamic patterns of adherence suggesting variation in the degree of behavioral change.

Aged↗

Uneasy promises: sexuality, health, and human rights.

Although attention to the links between health and human rights is growing globally, the full potential of a progressive human rights approach to health has not yet been explored, and it is even more faintly understood in the United States than in the rest of the world. At the same time, global claims for sexual rights, particularly for those identifying as gay, lesbian, transsexual, or bisexual, are increasingly being made as human rights claims. All of these approaches to rights advocacy risk limiting their own transformative impact unless advocates critique their own strategies. Paradoxically, using health as a way to bring attention to nonheteronormative sexualities can be both helpful and potentially dangerous, especially when coupled with human rights. Recognizing sexuality as a critical element of humanity, and establishing a fundamental human right to health, can play a role in broader social justice claims, but the tendency of both public health and human rights advocacy to "normalize" and regulate must be scrutinized and challenged.

Criminal Law↗

Post-cardiac transplantation gout: incidence of therapeutic complications.

OBJECTIVE: To study the clinical impact of gout treatment following cardiac transplantation. METHODS: We performed an audit of all cardiac transplant recipients of the Alfred Hospital before August 1998 who lived in Victoria. RESULTS: We studied 225 patients (81% men), with a mean post-transplant follow-up of 50.8 months (SD 36). Forty-three (19%) had pre-transplant gout, 19 recurring post-transplantation. Twenty-three patients developed gout de novo. Of the 24 patients who received allopurinol, 6 developed pancytopenia and required hospitalization. Fourteen received a change in immunosuppression: in 5 patients following pancytopenia, and in 9 to enable safe use of allopurinol. Thirty-two patients received colchicine; 5 developed neuromyopathy. Impaired renal function, diuretic use, and hypertension were more common in this sub-group. Non-steroidal anti-inflammatory agents, used in 16 patients, caused serious complications in 1 patient (life-threatening peptic ulceration and hemorrhage, precipitating dialysis-dependent chronic renal failure). CONCLUSIONS: Cardiac transplant recipients, when treated for gout, are at high risk of therapeutic complications. Thus, gout treatment significantly affects care, health, and immunosuppression of these patients.

Adolescent↗

Sexual but not reproductive: exploring the junction and disjunction of sexual and reproductive rights.

Although the term "sexual rights" has gained widespread currency, its concrete scope and content have not yet been fully defined. The need for definition is critical not only for promoting governmental accountability but also for ensuring that sexual rights can be claimed by diverse persons around the world. Ironically, the concept of "sexual and reproductive rights" poses a challenge to this effort; practices and people not traditionally addressed by reproductive rights work must be explicitly named and protected. This article considers how international norms have contributed to a gendered regulation of sexuality and of contemporary theories of "socially constructed sexuality," and it proposes a focus on the conditions that contribute to the ability to choose and on the links between sexuality, conduct, identity, social structures, and reproduction. Given the probable politically charged responses, global coalition-building is needed.

Human Rights↗

Identification and immunolocalization of actin cytoskeletal components in light- and dark-adapted octopus retinas.

Photoreceptors in the octopus retina are of the rhabdomeric type, with rhabdomeres arising from the plasma membrane on opposite sides of the cylindrical outer segment. Each rhabdomere microvillus has an actin filament core, but other actin-binding proteins have not been identified. We used immunoblotting techniques to identify actin-binding proteins in octopus retinal extracts and immunofluorescence microscopy to localize the same proteins in fixed tissue. Antibodies directed against alpha-actinin and vinculin recognized single protein bands on immunoblots of octopus retinal extract with molecular weights comparable to the same proteins in other tissues. Anti-filamin identified two closely spaced bands similar in molecular weight to filamin in other species. Antibodies to the larger of the Drosophila ninaC gene products, p174, identified two bands lower in molecular weight than p174. Anti-villin localized a band that was significantly less in molecular weight than villin found in other cells. Epifluorescence and confocal microscopy were used to map the location of the same actin-binding proteins in dark- and light-adapted octopus photoreceptors and other retinal cells. Antibodies to most of the actin-binding proteins showed heavy staining of the photoreceptor proximal/supportive cell region accompanied by rhabdom membrane and rhabdom tip staining, although subtle differences were detected with individual antibodies. In dark-adapted retinas anti-alpha-actinin stained the photoreceptor proximal/supportive cell region where an extensive junctional complex joins these two cell types, but in the light, immunoreactivity extended above the junctional complex into the rhabdom bases. Most antibodies densely stained the rhabdom tips but anti-villin exhibited a striated pattern of localization at the tips. We believe that the actin-binding proteins identified in the octopus retina may play a significant role in the formation of new rhabdomere microvilli in the dark. We speculate that these proteins and actin remain associated with an avillar membrane that connects opposing sets of rhabdomeres in light-adapted retinas. Association of these cytoskeletal proteins with the avillar membrane would constitute a pool of proteins that could be recruited for rapid microvillus formation from the previously avillar region.

Actinin↗

Limited erythropoietic response to combined treatment with recombinant human interleukin 3 and erythropoietin in myelodysplastic syndrome.

Twenty-two patients with myelodysplastic syndrome were treated with combined recombinant human erythropoietin and recombinant human interleukin 3 (rHuIL-3). All 22 patients were evaluable for toxicity and 21/22 for response. Thirteen patients (62%) required rHuIL-3 dose reduction because of toxicity. Nineteen experienced a 50% or greater rise in neutrophil count. Of seven patients with initial platelet counts of > 100,000, three experienced increases of > 15,000/ml while an equal number had a comparable decline. Five patients (21%) experienced a significant rise in reticulocyte count, and two transfusion-dependent patients experienced a significant decrease in transfusions. Erythroid burst-forming units were increased by > or = 50% in nine of 11 patients after combined therapy. Similar changes were seen in multipotential colony-forming units. Clinical responses were comparable to results obtained with epo alone while toxicities due to IL-3 were significant.

Aged↗

The pretectum mediates rapid eye movement sleep regulation by light.

A variety of sensory stimuli (e.g., visual, auditory, and thermal) are known to induce rapid eye movement (REM) sleep in mammals. Studies have examined the induction of REM sleep in albino rats by light-to-dark transitions, a phenomenon referred to as REM sleep triggering. Recent research has demonstrated that aspiration lesions of the superior colliculus (SC) and pretectal area attenuated REM sleep triggering. To define more specifically the area or areas involved in mediating REM sleep responses to changes in illumination, fiber-sparing neurotoxic lesions were made to the pretectum (PT) or the SC. Lesions of the PT attenuated REM sleep triggering, whereas lesions of the SC did not. Thus, the role of the PT may be expanded to include the regulation of REM sleep in response to photic stimulation in albino rats. These findings provide a paradigm in which to study mechanisms of REM sleep generation and the effects of light on behavioral state.

Animals↗

Anticoagulant therapy, anti-platelet agents and gastrointestinal endoscopy.

BACKGROUND: The increasing use of anticoagulant therapy and anti-platelet agents in the primary and secondary prevention of cardiovascular, cerebrovascular and venous thromboembolic disease has increased the need for guidelines for managing these agents prior to gastrointestinal endoscopy, particularly if therapeutic manoeuvres are required. The continuation of anticoagulant therapy increases the risk of haemorrhagic complications of gastrointestinal endoscopy. Temporary suspension of anticoagulant therapy exposes the patient to the risk of thromboembolism associated with the underlying condition requiring anticoagulant treatment. CONCLUSIONS: This article reviews the literature and proposes guidelines for the management of patients taking anticoagulant and anti-platelet agents who require gastrointestinal endoscopy.

Anticoagulants↗

Women's occupations, energy expenditure, and cardiovascular risk factors.

The purpose of this study was to examine the cardiovascular risk factors and energy expenditure of women from occupations that differ by physical activity level and socioeconomic level. Participants included 171 women randomly selected from employee lists at 10 employment sites. Measures included blood pressure, body mass index, levels of total and high-density lipoprotein (HDL) cholesterol, a submaximal aerobic fitness test on a bicycle ergometer, and a 12-month retrospective self-report of occupational, leisure time, and household energy expenditure. Women in active occupations had lower total cholesterol and higher HDL cholesterol than women in sedentary occupations. Women with higher occupational energy expenditure scores had higher HDL cholesterol and lower total cholesterol than women with lower occupational energy scores. Findings suggest that cardiovascular benefits, particularly for lipid profiles, may be derived from even small increases in occupational physical activity. The workplace may offer an environment for initiating policies to facilitate increased physical activity among women.

Activities of Daily Living↗

The superior colliculus-pretectum mediates the direct effects of light on sleep.

Light and dark have immediate effects on sleep and wakefulness in mammals, but the neural mechanisms underlying these effects are poorly understood. Lesions of the visual cortex or the superior colliculus-pretectal area were performed in albino rats to determine retinorecipient areas that mediate the effects of light on behavior, including rapid eye movement sleep triggering by lights-off and redistribution of non-rapid eye movement sleep in short light-dark cycles. Acute responses to changes in light conditions were virtually eliminated by superior colliculus-pretectal area lesions but not by visual cortex lesions. Circadian entrainment was evident in both groups with lesions and in normal controls. Thus, acute light-dark effects on sleep and wakefulness appear to be mediated independently from cortical vision or circadian rhythms.

Animals↗