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Biomedical subjects

J Miller

Publications and source records attributed to J Miller.

At least 37 records · Page 2Linked to original sources
PubMed2005

Transplantation for the treatment of intra-abdominal fibromatosis.

MATERIALS AND METHODS: During the last 9 years we treated 14 patients with a diagnosis of intra-abdominal fibromatosis. The 11 patients who received an intestinal allograft included isolated intestine (n = 6), liver-intestine (n = 1), intestine-kidney (n = 1), multivisceral (n = 1), multivisceral-kidney (n = 1), multivisceral-no liver (n = 1). Three patients received an intestinal autograft after partial abdominal evisceration and ex vivo tumor resection. Three patients additionally underwent an abdominal wall allograft. RESULTS: At follow-up until August 2004, all autotransplant patients are alive. Four intestinal transplant patients died within the first postoperative month. There were three graft losses. A patient who lost his graft early postoperatively was retransplanted but died of sepsis shortly there after. Two more patients lost their graft due to severe rejection and were retransplanted successfully. Two patients developed desmoid tumor recurrence in their abdominal or thoracic wall. Ten patients are alive 1 to 9 years posttransplantation. Nine have fully functioning grafts and one patient requires TPN supplementation at night due to dysmotility of her autograft. CONCLUSION: Intestinal allo-, or autotransplantation combined with transplantation of the abdominal wall can be lifesaving for patients suffering from extensive intra-abdominal fibromatosis.

Fibromatosis, Abdominal↗
PubMed2005

Conversion of stable kidney transplant recipients from a twice daily Prograf-based regimen to a once daily modified release tacrolimus-based regimen.

UNLABELLED: Modified release (MR) tacrolimus is an extended release formulation administered once daily (qD). The purpose of this pharmacokinetic (PK) study was to evaluate tacrolimus exposure in stable kidney transplant recipients converted from Prograf twice a day to MR tacrolimus qD. METHODS: This was an open-label, multicenter study with a crossover design. Eligible patients were 18 to 65 years of age, more than 6 months posttransplant with stable renal function, and received stable Prograf doses more than 2 weeks prior to enrollment. Patients received Prograf twice a day through day 7; 24-hour PK profiles were obtained on days 1 and 7. Patients were converted to the same milligram-for-milligram daily dose of MR tacrolimus qD in the morning on day 8; 24-hour PK profiles were obtained for MR tacrolimus on days 8, 14, and 21. Laboratory and safety parameters were also evaluated. RESULTS: Most patients (67 of 70) completed all 5 PK profiles. The 90% confidence intervals (CI) for the MR tacrolimus vs Prograf comparison at steady state (days 14 and 21 vs days 1 and 7) were 90.7 and 99.4 for AUC0-24 and 82.7 and 91.9 for Cmin. MR tacrolimus was well tolerated with a safety profile comparable to that of Prograf. AUC0-24 was highly correlated to Cmin for Prograf (day 1, r = 0.80; day 7, r = 0.84) and MR tacrolimus (day 14, r = 0.92; day 21, r = 0.86). Renal function remained stable after conversion to MR tacrolimus. CONCLUSION: The steady state PK of MR tacrolimus are equivalent to Prograf after a milligram-for-milligram conversion in stable kidney transplant recipients. The results provide evidence to support a safe 1:1 conversion from Prograf twice a day to MR tacrolimus.

Adult↗
PubMed2005

Shielding and fragmentation studies.

Radiation dosimetry for manned spaced missions depends on the ability to adequately describe the process of high-energy ion transport through many materials. Since the types of possible nuclear interactions are many and complex, transport models are used which depend upon a reliable source of experimental data. To expand the heavy ion database used in the models we have been measuring charge-changing cross sections and fragment production cross sections from heavy-ion interactions in various elementa targets. These include materials flown on space missions such as carbon and aluminium, as well as those important in radiation dosimetry such as hydrogen, nitrogen and water. Measuring heavy-ion fragmentation through these targets also gives us the ability to determine the effectiveness of new materials proposed for shielding such as graphite composites and polyethylene hybrids. Measurement without a target present gives an indication of the level of contamination of the primary beam, which is also important in radiobiology experiments.

Construction Materials↗
PubMed2005

Human immune response to a plague vaccine comprising recombinant F1 and V antigens.

The human immune response to a new recombinant plague vaccine, comprising recombinant F1 (rF1) and rV antigens, has been assessed during a phase 1 safety and immunogenicity trial in healthy volunteers. All the subjects produced specific immunoglobulin G (IgG) in serum after the priming dose, which peaked in value after the booster dose (day 21), with the exception of one individual in the lowest dose level group, who responded to rF1 only. Three subjects, found to have an anti-rV titer at screening, were excluded from the overall analysis. Human antibody functionality has been assessed by quantification of antibody competing for binding to rV in vitro and also by the transfer of protective immunity in human serum into the naive mouse. Human and macaque IgG competed for binding to rV in vitro with a mouse monoclonal antibody, previously shown to protect mice against challenge with plague, suggesting that this protective B-cell epitope on rV is conserved between these three species. Total IgG to rV in individuals and the titer of IgG competing for binding to rV correlated significantly at days 21 (r = 0.72; P < 0.001) and 28 (r = 0.82; P < 0.001). Passive transfer of protective immunity into mice also correlated significantly with total IgG titer to rF1 plus rV at days 21 (r(2) = 98.6%; P < 0.001) and 28 (r(2) = 76.8%; P < 0.03). However, no significant vaccination-related change in activation of peripheral blood mononuclear cells was detected at any time. Potential serological immune correlates of protection have been investigated, but no trends specific to vaccination could be detected in cellular markers.

Adult↗
PubMed2005

Minimally invasive, direct, real time measurement of drug concentration in the anterior eye.

AIMS: To evaluate a corneal contact lens which effectively turns the anterior chamber of the eye into a cuvette, enabling the concentration of a drug to be measured using absorption spectroscopy. METHODS: A hand held contact lens incorporating optical fibres connected to a spectrograph enabled a beam of light to be directed in, across, and out of the anterior chamber. The device was used to follow the time course of drug concentration in the anterior chamber of rabbit (sedated) and humans, using topical brimonidine or fluorescein (with or without local anaesthesia). Absorbance measurements were taken for a 5-25 second period, repeated every 30 minutes. Drug concentrations were compared using absorbance peak height. RESULTS: Corneal absorption starts to rise rapidly at wavelengths shorter than 315 nm. The light path within the anterior chamber is 6.9 mm (rabbit) and 5.8 mm (human), the absorbance measured also includes a corneal component. Application of fluorescein (three drops of 2% solution) in rabbit allowed detection, 60 minutes later, of a large absorbance peak at 490 nm. In the human eye, the device could not measure fluorescein (applied as in rabbit), but clearly detected brimonidine for 3 hours following topical application of 0.6 mg. Modification of the device to measure fluorescence resulted in the detection of 5.3 nM fluorescein in the ex vivo rabbit eye, an increase in sensitivity of two orders of magnitude over the absorption measurements. CONCLUSION: This device has the potential to allow repeated measurements of drug concentrations in the anterior eye provided the drug has suitable absorption or fluorescence characteristics.

Absorption↗
PubMed2005

Cytogenetic effects of high-energy iron ions: dependence on shielding thickness and material.

We report results for chromosomal aberrations in human peripheral blood lymphocytes after they were exposed to high-energy iron ions with or without shielding at the HIMAC, AGS and NSRL accelerators. Isolated lymphocytes were exposed to iron ions with energies between 200 and 5000 MeV/nucleon in the 0.1-1-Gy dose range. Shielding materials consisted of polyethylene, lucite (PMMA), carbon, aluminum and lead, with mass thickness ranging from 2 to 30 g/cm2. After exposure, lymphocytes were stimulated to grow in vitro, and chromosomes were prematurely condensed using a phosphatase inhibitor (calyculin A). Aberrations were scored using FISH painting. The yield of total interchromosomal exchanges (including dicentrics, translocations and complex rearrangements) increased linearly with dose or fluence in the range studied. Shielding decreased the effectiveness per unit dose of iron ions. The highest RBE value was measured with the 1 GeV/nucleon iron-ion beam at NSRL. However, the RBE for the induction of aberrations apparently is not well correlated with the mean LET. When shielding thickness was increased, the frequency of aberrations per particle incident on the shield increased for the 500 MeV/nucleon ions and decreased for the 1 GeV/nucleon ions. Maximum variation at equal mass thickness was obtained with light materials (polyethylene, carbon or PMMA). Variations in the yield of chromosomal aberrations per iron particle incident on the shield follow variations in the dose per incident particle behind the shield but can be modified by the different RBE of the mixed radiation field produced by nuclear fragmentation. The results suggest that shielding design models should be benchmarked using both physics and biological data.

Chromosome Aberrations↗
PubMed2005

Immunosuppressive treatment options in renal transplantation.

An overview of the first 4 decades of clinical kidney transplantation would characterize progress primarily in the development of new immunosuppressive agents designed to reduce the incidence and severity of acute rejection to improve short-term outcomes, but with less marked effects on long-term patient and graft survival. The new trend of immunosuppressive therapy is to facilitate long-term allograft and patient survival, and to help to maintain a good quality of life after renal transplantation. To achieve these goals, transplant physicians need to determine the immunosuppressive protocols that will best minimize risk factors associated with reduced allograft/patient survival and quality of life. Recent protocols and clinical experience with modern immunosuppression strategies, as well as the efficacy and safety of various combination protocols, will be reviewed.

Adrenal Cortex Hormones↗
PubMed2004

Mouse model characterisation for anthrax vaccine development: comparison of one inbred and one outbred mouse strain.

In order to evaluate the immunogenicity and protective efficacy of anthrax vaccine candidates a suitable small animal model is required. The inbred A/J strain of mouse has been selected as a potential model, and its immune response to immunisation with recombinant protective antigen (rPA) vaccine characterised, by assessment of rPA specific antibody production, and protection against injected challenge, with the unencapsulated STI strain of Bacillus anthracis. Studies were conducted to determine the time required post immunisation to develop a protective immune response, to define the minimum protective dose of vaccine required and to assess the long-term immune response to immunisation. From the results of these studies it was possible to establish that the A/J mouse is a consistent and robust small animal model for rPA vaccine testing. A comparison of the immune response to rPA vaccine immunisation in the Turner Outbred (TO) mouse strain was also conducted. Both inbred and outbred mouse strains displayed a predominantly Th2 biased immune response and showed a comparable antibody response to rPA immunisation. An assessment of protection in the TO mouse against aerosol challenge with the fully virulent strain of B. anthracis, Ames, was also made.

Animals↗
PubMed2004

Plasma homocysteine levels and risk of Alzheimer disease.

OBJECTIVE: To explore the association between high homocysteine levels and risk of Alzheimer disease (AD) in the Washington Heights-Inwood Columbia Aging Project (WHICAP). METHODS: The authors obtained fasting plasma samples in 909 elderly subjects chosen at random from a cohort of Medicare recipients; there was longitudinal data in 679 subjects without dementia at baseline who were followed for 3,206 person-years. Prevalent and incident dementia and its subtypes were diagnosed using standard methods. RESULTS: There were 128 persons with prevalent AD and 109 with incident AD in 3,206 person-years of follow-up. The adjusted OR of prevalent AD for the highest quartile of homocysteine compared to the lowest was 1.3 (95% CI = 0.7, 2.3; p for trend = 0.25). In longitudinal analyses, the authors found that the adjusted hazard ratio of AD for the highest quartile of homocysteine was 1.4 (95% CI = 0.8, 2.4; p for trend = 0.31). The authors also found that high homocysteine levels were not related to a decline in memory scores over time. Age was a significant confounder in all the analyses. The study had 80% power to detect a hazard ratio of 1.3 in the longitudinal analyses. CONCLUSION: High homocysteine levels were not associated with AD and were not related to a decrease in memory scores over time.

Age Factors↗
PubMed2004

The ALTEA/ALTEINO projects: studying functional effects of microgravity and cosmic radiation.

The ALTEA project investigates the risks of functional brain damage induced by particle radiation in space. A modular facility (the ALTEA facility) is being implemented and will be operated in the International Space Station (ISS) to record electrophysiological and behavioral descriptors of brain function and to monitor their time dynamics and correlation with particles and space environment. The focus of the program will be on abnormal visual perceptions (often reported as "light flashes" by astronauts) and the impact on retinal and brain visual structures of particle in microgravity conditions. The facility will be made available to the international scientific community for human neurophysiological, electrophysiological and psychophysics experiments, studies on particle fluxes, and dosimetry. A precursor of ALTEA (the 'Alteino' project) helps set the experimental baseline for the ALTEA experiments, while providing novel information on the radiation environment onboard the ISS and on the brain electrophysiology of the astronauts during orbital flights. Alteino was flown to the ISS on the Soyuz TM34 as part of mission Marco Polo. Controlled ground experiments using mice and accelerator beams complete the experimental strategy of ALTEA. We present here the status of progress of the ALTEA project and preliminary results of the Alteino study on brain dynamics, particle fluxes and abnormal visual perceptions.

Brain↗
PubMed2004

Effects of heavy ions on visual function and electrophysiology of rodents: the ALTEA-MICE project.

ALTEA-MICE will supplement the ALTEA project on astronauts and provide information on the functional visual impairment possibly induced by heavy ions during prolonged operations in microgravity. Goals of ALTEA-MICE are: (1) to investigate the effects of heavy ions on the visual system of normal and mutant mice with retinal defects; (2) to define reliable experimental conditions for space research; and (3) to develop animal models to study the physiological consequences of space travels on humans. Remotely controlled mouse setup, applied electrophysiological recording methods, remote particle monitoring, and experimental procedures were developed and tested. The project has proved feasible under laboratory-controlled conditions comparable in important aspects to those of astronauts' exposure to particle in space. Experiments are performed at the Brookhaven National Laboratories [BNL] (Upton, NY, USA) and the Gesellschaft für Schwerionenforschung mbH [GSI]/Biophysik (Darmstadt, FRG) to identify possible electrophysiological changes and/or activation of protective mechanisms in response to pulsed radiation. Offline data analyses are in progress and observations are still anecdotal. Electrophysiological changes after pulsed radiation are within the limits of spontaneous variability under anesthesia, with only indirect evidence of possible retinal/cortical responses. Immunostaining showed changes (e.g. increased expression of FGF2 protein in the outer nuclear layer) suggesting a retinal stress reaction to high-energy particles of potential relevance in space.

Animals↗
PubMed2004

Viral interleukin-10 gene therapy to induce tolerance to solid organ transplants in mice.

In this study, a novel gene therapy approach to prolong allograft survival was designed. Autologous (syngeneic) hematopoietic stem cell-enriched bone marrow cells (HSC; lin(-)) engineered with the vIL-10 gene (vIL-10-HSC) were injected (4 to 6 x 10(6) cells, i.v.) into lethally (9.5 Gy) or sublethally (4 Gy) irradiated CBA/J mice 6 weeks prior to allogeneic heart (C57BL/6) transplantation (Tx). Cardiac allograft survival was significantly (P <.004) prolonged in lethally (71 +/- 40 days) and sublethally (114 +/- 15 days) irradiated mice that received vIL-10-HSC compared to controls that received no HSC (11 +/- 1 days), unengineered HSC, or vector-DNA-engineered HSC (12 to 16 days). Tolerant graft histopathology demonstrated mild arteritis/venulitis (grade 0.7) and rejection (grade 1.0). Intragraft expression of costimulatory molecules (B7.1, B7.2), cytokines (IL-2, IL-4, mIL-10, IFN-gamma), and iNOS molecules were markedly lower in tolerant grafts that survived for >100 days; recipient T lymphocytes demonstrated hyporeactivity to donor and third-party antigens in mixed lymphocyte cultures. These findings have important implications and potential therapeutic applications in transplantation and autoimmune diseases.

Animals↗
PubMed2004

Use of cyclosporine in renal transplantation.

Since 1983, cyclosporine has been the backbone of immunosuppression in clinical organ transplantation. Cyclosporine is usually used in combination with steroids and with another second-line immunosuppressant like azathioprine or mycofenolate mofetil. With these regimens, graft survival at 1 year exceeds 90% and long-term results are excellent. The main complication is renal toxicity, which is usually secondary to excessive exposure. The new microemulsion formulation of cyclosporine, introduced in recent years, has improved intestinal absorption and bioavailability and resulted in much less intrapatient variation than the older formulation. The introduction of 2-hour peak blood level monitoring, which corresponds closely to the area under the curve of the drug, allows more appropriate dosing, thus minimizing rejection owing to underexposure or toxicity owing to overexposure. As new effective immunosuppressants are currently becoming available for use in combination with cyclosporine, the transplant community can look forward to more effective and safer immunosuppression.

Azathioprine↗
PubMed2004

Endometrial stromal sarcoma resembling adenomyosis and menstrual-phase endometrium.

BACKGROUND: Low-grade endometrial stromal sarcoma (LGESS) and endometriosis are two conditions of different prognostic significance that are usually not difficult to distinguish histologically. CASE: We present the case of a 38-year-old woman who underwent laparotomy after a diagnosis of endometrial stromal neoplasm on uterine curettings. Uterine enlargement and regional and paraaortic lymphadenopathy were found. Pathology showed adenomyotic-like myometrial hypertrophy and menstrual-like shedding of tumor in involved lymph nodes. The finding of large areas of endometrial stromal cells without accompanying glands forming tumorous masses in both sites supported the diagnosis of LGESS. We believe that this is the first time that these phenomena have been reported in LGESS. CONCLUSION: In these cases, adenomyotic myometrial hypertrophy and menstrual shedding have been used to distinguish endometriosis from LGESS, but do not appear to be absolute criteria. Endometriosis and LGESS are undoubtedly separate entities, but occasionally may resemble each other.

Adult↗
PubMed2004

Recruitment, engagement, and retention of people living with HIV and co-occurring mental health and substance use disorders.

People living with HIV/AIDS who have both a co-occurring mental health diagnosis and a substance use disorder (individuals with triple diagnoses) frequently do not receive adequate treatment for one or more of their illnesses. Poverty, risky behaviours, vacillating motivation, and cognitive impairments are additional problems facing many individuals with triple diagnoses. In many communities the service system is inadequately prepared to serve this population. Treatment barriers include stigma associated with the three illnesses, separate funding streams, and lack of co-ordination between medical, mental health, and substance abuse treatment facilities. This paper discusses strategies for recruiting, engaging, and retaining individuals with triple diagnoses in both treatment and research. Recruitment strategies should be directed at both professionals and individuals with triple diagnoses themselves. Recruiting and engaging these individuals in treatment requires that comprehensive services be provided on a 24-hour basis in a flexible and culturally competent manner. A team approach is often the most effective way of providing such services. Retaining individuals with triple diagnoses in a longitudinal research study requires multiple strategies including the collection of detailed tracking information, outreach workers, and financial incentives for completing the interviews.

Adolescent↗
PubMed2004

Characteristics of women who deliver with no prenatal care.

OBJECTIVE: To compare the characteristics, morbidities and pregnancy outcomes of women with no prenatal care and women receiving some care. METHODS: Medical records were abstracted for demographic variables as well as information concerning substance abuse, sexually transmitted diseases and perinatal outcome. Bivariate associations of descriptive data were tested using odds ratios or Fisher's exact test. Multivariate analysis determined adjusted odds ratios. Significance was set at alpha=0.05. RESULTS: Women who received no prenatal care were more likely to be multiparous, living with at least one child, less educated, uninsured, smoke, use cocaine and have a prior history of substance abuse. Preterm labor, preterm delivery, low birth weight and stillbirth were more common. Syphilis and HIV were found in nearly 5% of women without care. CONCLUSION: Intensive interventions are needed for women who fail to receive prenatal care so as to link these high-risk women to needed services.

Adult↗
PubMed2004

Radiofrequency ablation of airway smooth muscle for sustained treatment of asthma: preliminary investigations.

Bronchial thermoplasty is a procedure now being tested in humans for the treatment of asthma. Current studies focusing on safety are encouraging. The procedure, which causes extensive ablation of airway smooth muscle (ASM), is well tolerated, and there is a sustained reduction in airway responsiveness to methacholine. Two assumptions underlie the development of this procedure: 1) ASM is a vestigial tissue; and 2) that treatment directed at ASM alone will provide sustained symptomatic and physiological improvement in asthmatic humans. Even if this procedure is efficacious, it must be safe in the long-term. Current studies in animals and humans suggest that this is very likely to be the case. While bronchial thermoplasty may have a broad application, especially for patients who wish for a permanent amelioration of their symptoms or have difficulty adhering to medical regimens, the compelling use of this procedure is for patients who are inadequately controlled on current drug therapy or who cannot adhere to therapeutic regimens. The application of this procedure for the treatment of asthma is currently being considered by regulatory agencies, and study centres are currently disseminated throughout North America and Europe. Within the next 1-2 yrs, a profile of the potential role of this therapy in human asthma should be developed fully.

Animals↗