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Biomedical subjects

J Miller

Publications and source records attributed to J Miller.

At least 145 records · Page 8Linked to original sources

Using the jackknife-based scoring method for measuring LRP onset effects in factorial designs.

Miller, Patterson, and Ulrich (1998) introduced a jackknife-based method for measuring the differences between two conditions in the onset latencies of the lateralized readiness potential (LRP). The present paper generalizes such jackknife-based methods to factorial experiments with any combination of within- and between subjects factors. Specifically, we introduce a subsample scoring method to assess potential main and interaction effects on LRP onsets within conventional yet slightly adjusted analyses of variance (ANOVAs) and post hoc comparison procedures.

Adult↗

Shielded Heavy-Ion Environment Linear Detector (SHIELD): an experiment for the Radiation and Technology Demonstration (RTD) Mission.

Radiological assessment of the many cosmic ion species of widely distributed energies requires the use of theoretical transport models to accurately describe diverse physical processes related to nuclear reactions in spacecraft structures, planetary atmospheres and surfaces, and tissues. Heavy-ion transport models that were designed to characterize shielded radiation fields have been validated through comparison with data from thick-target irradiation experiments at particle accelerators. With the RTD Mission comes a unique opportunity to validate existing radiation transport models and guide the development of tools for shield design. For the first time, transport properties will be measured in free-space to characterize the shielding effectiveness of materials that are likely to be aboard interplanetary space missions. Target materials composed of aluminum, advanced composite spacecraft structure and other shielding materials, helium (a propellant) and tissue equivalent matrices will be evaluated. Large solid state detectors will provide kinetic energy and charge identification for incident heavy-ions and for secondary ions created in the target material. Transport calculations using the HZETRN model suggest that 8 g cm -2 thick targets would be adequate to evaluate the shielding effectiveness during solar minimum activity conditions for a period of 30 days or more.

Computer Simulation↗

Recent measurements for hadrontherapy and space radiation: nuclear physics.

The particles and energies commonly used for hadron therapy overlap the low end of the charge and energy range of greatest interest for space radiation applications, Z=1-26 and approximately 100-1000 MeV/nucleon. It has been known for some time that the nuclear interactions of the incident ions must be taken into account both in treatment planning and in understanding and addressing the effects of galactic cosmic ray ions on humans in space. Until relatively recently, most of the studies of nuclear fragmentation and transport in matter were driven by the interests of the nuclear physics and later, the hadron therapy communities. However, the experimental and theoretical methods and the accelerator facilities developed for use in heavy ion nuclear physics are directly applicable to radiotherapy and space radiation studies. I will briefly review relevant data taken recently at various accelerators, and discuss the implications of the measurements for radiotherapy, radiobiology and space radiation research.

Cosmic Radiation↗

Creation and utilization of a World Wide Web based space radiation effects code: SIREST.

In order for humans and electronics to fully and safely operate in the space environment, codes like HZETRN (High Charge and Energy Transport) must be included in any designer's toolbox for design evaluation with respect to radiation damage. Currently, spacecraft designers do not have easy access to accurate radiation codes like HZETRN to evaluate their design for radiation effects on humans and electronics. Today, the World Wide Web is sophisticated enough to support the entire HZETRN code and all of the associated pre and post processing tools. This package is called SIREST (Space Ionizing Radiation Effects and Shielding Tools). There are many advantages to SIREST. The most important advantage is the instant update capability of the web. Another major advantage is the modularity that the web imposes on the code. Right now, the major disadvantage of SIREST will be its modularity inside the designer's system. This mostly comes from the fact that a consistent interface between the designer and the computer system to evaluate the design is incomplete. This, however, is to be solved in the Intelligent Synthesis Environment (ISE) program currently being funded by NASA.

Algorithms↗

Donor bone marrow-derived chimeric cells present in renal transplant recipients infused with donor marrow. I. Potent regulators of recipient antidonor immune responses.

BACKGROUND: Even though a number of transplant centers have adopted donor-specific bone marrow cell (DBMC) infusions to enhance donor cell chimerism, to date there has been no direct evidence linking chimerism with tolerance induction in human organ transplant recipients. METHODS: Cells of donor phenotype were isolated 1 year postoperatively from the peripheral blood lymphocytes and iliac crest bone marrow of 11 living-related-donor (LRD) renal transplant recipients, who had received perioperative donor bone marrow cell infusions. These recipient-derived donor (RdD) cells were characterized phenotypically by flow cytometric analysis and functionally as modulators in mixed lymphocyte reaction (MLR) and cell-mediated lympholysis (CML) assays. RESULTS: The yield of RdD cells ranged from 0.1 to O.9% of the starting material with the majority being TcRalphabeta, CD3 positive T cells, a substantial percentage of which coexpressed CD28. At 1 year posttransplant almost 50% of the LRD-kidney/DBMC recipients tested so far exhibited donor-specific unresponsiveness in MLR (7/17) and CML (6/13) reactions and this trend was further enhanced at 23 years. In the recipients with residual positive antidonor immune responses, the RdD cells inhibited recipient antidonor MLR and CML responses significantly more strongly than freshly isolated and similarly treated iliac crest bone marrow cells from the donor. RdD cells also inhibited the MLR of the recipient to third party allogeneic stimulator cells; however, this nonspecific effect was significantly weaker than specific inhibition. We also established long-term bone marrow cultures stimulated every 2 weeks with irradiated alogeneic feeder cells, that had similar functional properties thus possibly providing us with an in vitro correlate the RdD cells. CONCLUSIONS: These results clearly support the notion that the infused donor cells play a positive role in the induction and/or maintenance of transplant tolerance.

Bone Marrow Transplantation↗

Involvement of multiple subpopulations of human bone marrow cells in the regulation of allogeneic cellular immune responses.

BACKGROUND: The identity of the cells in the human bone marrow that function as effective regulators of in vitro and possibly in vivo cellular immune responses is not well established. METHODS: Cell subpopulations were isolated from cadaver donor vertebral-body bone marrow cells (DBMC) by using immuno-magnetic microbeads and were tested as inhibitors (modulators) in cell-mediated lympholysis (CML) and mixed lymphocyte reaction (MLR) responses of normal peripheral blood lymphocytes stimulated with irradiated cadaver donor spleen cells. RESULTS: Compared with spleen cells as controls, un-irradiated T-cell depleted DBMC inhibited both the MLR and CML responses of allogeneic responder cells in a dose dependent manner (as in our previous reports). The inhibition was also mediated by a number of purified subpopulations including pluripotent CD34+ stem cells, and their CD34 negative early progeny of both lymphoid and myeloid lineages. These included DBMC enriched for non-T-cell lymphoid precursors (NT-LP/DBMC; i.e., DBMC depleted of CD3, CD15, and glycophorin-A positive cells) and DBMC positively selected for CD38+, CD2+, CD5+, and CD1+ lymphoid cells (all were depleted of CD3+ cells) as well as CD33+ (but CD15 negative) myeloid precursors. However, positively selected CD19+ B-cells and CD15+ myeloid cells did not inhibit the MLR and CML responses. The NT-LP/DBMC that had been repeatedly stimulated with irradiated allogeneic peripheral blood lymphocytes caused the strongest inhibition of the MLR and CML responses of the same allogeneic cells with 200 times fewer modulator cells needed than uncultured DBMC (P<0.001). Flow cytometric analysis revealed that majority of cells in these cell lines had become CD3+ TcR-alphabeta+ CD4+ and CD28+ cells. CONCLUSION: A variety of less differentiated cells of various lineages residing in the human bone marrow are immunoregulatory in vitro. Among them, there is at least one subset that can undergo differentiation in vitro into regulatory T cells that can be maintained in long-term cultures.

Antigens, CD34↗

Identification of residues in the carboxy-terminal domain of Clostridium perfringens alpha-toxin (phospholipase C) which are required for its biological activities.

A panel of random mutants within the DNA encoding the carboxy-terminal domain of Clostridium perfringens alpha-toxin was constructed. Three mutants were identified which encoded alpha-toxin variants (Lys330Glu, Asp305Gly, and Asp293Ser) with reduced hemolytic activity. These variants also had diminished phospholipase C activity toward aggregated egg yolk phospholipid and reduced cytotoxic and myotoxic activities. Asp305Gly showed a significantly increased enzymatic activity toward the monodisperse substrate rhoNPPC, whereas Asp293Ser displayed a reduced activity toward this phospholipid analogue. In addition, Asp293Ser showed an increased dependence on calcium for enzymatic activity toward aggregated phospholipid and appeared calcium-depleted in PAGE band-shift assays. In contrast, neither Lys330Glu nor Asp305Gly showed altered dependence on calcium for enzymatic activity toward aggregated phospholipid. Asp305 is located in the interface between the amino- and carboxy-terminal domains, whereas Asp293 and Lys330 are surface exposed residues which may play a role in the recognition of membrane phospholipids.

Amino Acid Substitution↗

Environmental control to reduce transmission of Clostridium difficile.

Restrictive antibiotic policies and infection control measures have been shown to reduce the incidence of Clostridium difficile-associated diarrhea (CDAD) among hospitalized patients. To date, the role of environmental disinfectants in reducing nosocomial CDAD rates has not been well studied. In a before-and-after intervention study, patients in 3 units were evaluated to determine if unbuffered 1:10 hypochlorite solution is effective as an environmental disinfectant in reducing the incidence of CDAD. Among 4252 patients, the incidence rate of CDAD for bone marrow transplant patients decreased significantly, from 8.6 to 3.3 cases per 1000 patient-days (hazard ratio, 0.37; 95% confidence interval, 0.19-0.74), after the environmental disinfectant was switched from quaternary ammonium to 1:10 hypochlorite solution in the rooms of patients with CDAD. Reverting later to quaternary ammonium solution increased the CDAD rate to 8.1 cases per 1000 patient-days. No reduction in CDAD rates was seen among neurosurgical intensive care unit and general medicine patients, for whom baseline rates were 3.0 and 1.3 cases per 1000 patient-days, respectively. Unbuffered 1:10 hypochlorite solution is effective in decreasing patients' risk of developing CDAD in areas where CDAD is highly endemic. Presumed mechanisms include reducing the environmental burden and the potential for C. difficile transmission among susceptible patients.

Adult↗

Successful surgical salvage of pancreas allografts after complete venous thrombosis.

BACKGROUND: Complete venous thrombosis of the pancreas after simultaneous pancreas-kidney (SPK) transplantation usually results in graft loss. We describe a technique that allows salvage of the graft after complete venous thrombosis. METHODS: A total of 150 patients with insulin dependent diabetes mellitus/end stage renal disease underwent SPK over the past decade at the University of Miami. Of these, three patients developed complete venous thrombosis after induction therapy with antiinterleukin-2R antibody and i.v. tacrolimus. These three patients underwent surgical thrombectomy followed by heparinization and oral anticoagulation. The splenic vein was opened distally at the tail of the pancreas and the superior mesenteric vein at the level of the mesentery or head of the pancreas. Thrombectomy was performed with a Fogarty catheter. The portal anastomosis was not opened or manipulated. The arterial "Y" graft was not clamped and the right iliac vein was controlled proximally with a double wrapped vessel-loop to contain possible thrombus. In one patient, the partially thrombosed splenic artery was opened at the tail of the pancreas and thrombectomy was performed in the same fashion. There were no apparent technical problems. A pancreatic biopsy was not performed, nor was acute rejection treated empirically. RESULTS: Intraoperative and serial Doppler ultrasound showed good flow through the allograft. In all three patients the exocrine and endocrine function of the pancreas was preserved with a mean follow-up of 15 months. CONCLUSIONS: The described surgical thrombectomy followed by systemic anticoagulation may be useful in the salvage of the allograft pancreas in case of complete venous thrombosis.

Adult↗

Safety and efficacy of tacrolimus in combination with mycophenolate mofetil (MMF) in cadaveric renal transplant recipients. FK506/MMF Dose-Ranging Kidney Transplant Study Group.

BACKGROUND: Tacrolimus (FK506) is a safe and effective treatment for the prevention of rejection of renal allografts. Mycophenolate mofetil (MMF) has been used as adjunct immunosuppressive therapy with cyclosporine and corticosteroids for the same purpose. The objective of this study was to investigate the safety and efficacy of FK506 and MMF in renal transplant recipients. METHODS: After cadaveric renal transplant, patients were randomized to receive tacrolimus in combination with either azathioprine (AZA, n=59), MMF 1 g/day (n=59), or MMF 2 g/day group (n=58). Patients were followed for 1 yr posttransplant for the incidence of biopsy-confirmed acute rejection, patient and graft survival, and adverse events. RESULTS: Tacrolimus doses and trough concentrations were similar between treatment groups at all time points; 80% of patients were maintained within a range of 5.0-13.9 ng/ml at 12 months posttransplant. The mean dose of MMF decreased in the 2 g/day group to 1.5 g/day by 6 months posttransplant, primarily due to gastrointestinal GI-related disorders. The incidence of biopsy-confirmed acute rejection at 1 year was 32.2%, 32.2%, and 8.6% in the AZA, MMF 1 g/day, and MMF 2 g/day groups, respectively (P<0.01). The use of antilymphocyte antibodies for the treatment of rejection was comparable across treatment groups. The incidence of most adverse events was similar across treatment groups and comparable with previous reports. The overall incidence of posttransplant diabetes mellitus was 11.9%, with the lowest rate observed in the MMF 2 g/day group (4.7%), and was reversible in 40% of patients. The incidence of malignancies and opportunistic infections was low and not different across treatment groups. CONCLUSION: Tacrolimus in combination with an initial dose of MMF 2 g/day is a very effective and safe regimen in cadaveric kidney transplant recipients.

Acute Disease↗

A syndrome of lipoatrophy, lactic acidaemia and liver dysfunction associated with HIV nucleoside analogue therapy: contribution to protease inhibitor-related lipodystrophy syndrome.

BACKGROUND: Lipodystrophy (LD; peripheral lipoatrophy, central adiposity) hyperlipidaemia and insulin resistance often complicate protease inhibitor-containing antiretroviral therapy. Lipoatrophy and abdominal distension were observed in protease inhibitor-naive nucleoside analogue reverse transcriptase inhibitor (NRTI) recipients with lactic acidaemia and hepatic impairment, which are known NRTI-induced mitochondrial toxicities. DESIGN AND SETTING: Case-control study in a university-based outpatient clinic. PATIENTS AND METHODS: The patients studied included 14 NRTI recipients with lipoatrophy, 32 antiretroviral-naive patients without LD, 28 NRTI recipients without LD, 44 combined NRTI-protease inhibitor recipients without LD, and 102 NRTI-protease inhibitor recipients with LD. Data was obtained on body composition (questionnaire, physical examination, dual-energy x-ray absorptiometry and abdominal computerized tomography), with biochemical, lipid and glycaemic parameters. RESULTS: The NRTI-LD syndrome was characterized by recent onset fatigue and nausea, peripheral lipoatrophy (6 kg loss over 4 months), abdominal distension (ascites +/- hepatomegaly) and elevated lactate (4.6, 1.1, 1.2, 1.4 and 1.7 mmol/l, respectively; P< 0.0001) and liver enzymes. Cases without hepatic involvement also had lower body fat and greater lactate than unaffected controls. Metabolic disturbances and weight improved after cessation. The NRTI-LD syndrome differed from protease inhibitor-related LD syndrome by the presence of recent onset symptoms and weight loss, higher lactate and alanine aminotransferase, and lower albumin, cholesterol, triglycerides, glucose and insulin. In treated controls, current stavudine therapy, protease inhibitor duration, and lactic acidaemia were independently associated with both lipoatrophy and abdominal obesity; total NRTI duration was also associated with lipoatrophy, and lamivudine and protease inhibitor duration with buffalo hump. CONCLUSIONS: A syndrome of lipoatrophy, constitutional illness, lactic acidaemia and hepatic dysfunction can complicate NRTI therapy. Both protease inhibitor and NRTI therapies, particularly if associated with lactic acidaemia, contribute to LD syndrome, but have some distinguishable clinical and metabolic effects.

Acidosis, Lactic↗

Inhibition of IL-4 responses after T cell priming in the context of LFA-1 costimulation is not reversed by restimulation in the presence of CD28 costimulation.

Costimulation is one of several factors that influence the differentiation of CD4+ Th cell responses. Previously, we have shown that Ag presentation in the context of LFA-1 costimulation by fibroblasts transfected with class II and ICAM-1 (ProAd-ICAM) can drive naive CD4-positive T cells into cell cycle, but these T cells die by apoptosis 4-5 days after stimulation. In this report we show that the death of these cells can be prevented by the addition of exogenous IL-2 (20 U/ml) or by restimulation with Ag presented in the context of CD28 costimulation. Under these conditions, T cells go through extensive cell division and normal cell expansion. However, when T cells that have been primed by Ag presented in the context of LFA-1 costimulation are restimulated, they secrete IL-2 and IFN-gamma, but little or no IL-4. The inability of ProAd-ICAM-primed T cells to produce IL-4 was restored by the addition of IL-4 to the priming culture. However, IL-4 responses were not restored by representation of Ag in the context of CD28 costimulation, even as early as 24 h after priming with Ag presented by ProAd-ICAM cells. These findings suggest that differential expression of B7-1 and ICAM-1 by APCs during the initiation of immune responses may alter the differentiation of Th populations.

Animals↗

Somatoform symptoms and treatment nonadherence in depressed family medicine outpatients.

OBJECTIVES: To examine whether somatoform symptoms, specifically symptoms of conversion, somatization, and hypochondriasis, are associated with side-effect reporting and treatment nonadherence in depressed family medicine outpatients, and to measure whether symptoms improve with pharmacotherapy. DESIGN: Inception cohort study with 14-week follow-up. SETTING: Inner-city family medicine residency clinic. PATIENTS: Thirty-nine consecutive adults with major depressive disorder were asked to participate, and 30 consented. INTERVENTION: Antidepressants for 14 weeks. MAIN OUTCOME MEASURES: The Personality Assessment Inventory (PAI) was administered before treatment. The PAI is a self-reported inventory compatible with the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, designed to measure a broad range of personality characteristics. After 14 weeks, the side-effect incidence and treatment nonadherence rates were determined, and 12 patients were readministered the PAI. RESULTS: Depressed family medicine patients demonstrated trends toward elevated Somatic Complaints scale and conversion subscale scores and a lower Suicidal Ideation scale score relative to those of a standardized depressed psychiatric patient profile. Conversion and hypochondriacal symptoms were associated with side-effect reporting and treatment nonadherence. Somatization and hypochondriacal symptoms improved clinically and statistically during treatment for depression. CONCLUSIONS: Somatoform distress is a complex, common, and understudied phenomenon in primary care that can adversely affect the treatment of depression. Somatoform symptoms of conversion and hypochondriasis, but not somatization, were found to be risk factors for treatment nonadherence. Somatization and hypochondriacal symptoms may represent personality states that improve with pharmacotherapy, and conversion symptoms may be a personality trait resistant to medical treatment for depression.

Adult↗

Vascular complications following bladder drained, simultaneous pancreas-kidney transplantation: the University of Miami experience.

Vascular complications remain a significant nonimmunologic source of pancreas allograft loss. From February 1993 through January 1998, we performed 98 simultaneous pancreas-kidney transplantations (SPK) using pancreatic exocrine bladder drainage in patients with type 1 insulin-dependent diabetes mellitus and end-stage renal disease. They originally received quadruple immunosuppression, and since May 1997 triple immunosuppression protocol (tacrolimus, mycophenolate mofetil, and steroids). The patients' mean age was 37 years (range 24-53 years), including 50 women and 48 men with a mean follow-up of 42 months. The overall rate of vascular complications was 6% (5 patients). The vascular complications were as follows: late thrombosis of the Y with persistent pancreas allograft function (n = 1), rupture of a pseudoaneurysm of the superior mesenteric artery (PSMA) with an arteriovenous fistula (AVF) (n = 1), thrombosis of the splenic vein (SV) (n = 3), complete thrombosis of the superior mesenteric vein (SMV) and splenic vein (n = 1). The patient with PSMA underwent surgical correction of the AVF and PSMA with preservation of the allograft pancreas function. The other patient with late thrombosis of the Y-graft required no treatment. All 3 patients with SV thrombosis were systemically heparinized followed by oral anticoagulation. The patient with complete thrombosis required surgical thrombectomy of the SMV and SV followed by heparinization and oral anticoagulation. All 6 patients including the 4 with thrombosis had preservation of the pancreas function. Serial pancreas ultrasound showed resolution and improvement with recanalization of the splenic vein and superior mesenteric vein in those patients with thrombosis. We describe our vascular experience with salvage of the pancreatic allograft function. Surgery seems to be the best treatment option in the case of AVF or complete thrombosis of the allograft. Intravenous heparin followed by oral anticoagultion could be a conservative approach for SV thrombosis.

Adult↗

Use of tacrolimus and mycophenolate mofetil as induction and maintenance in simultaneous pancreas-kidney transplantation.

Clinical trials using quadruple immunosuppression that include the combination of tacrolimus and mycophenolate mofetil have been shown to reduce the incidence of acute rejection episodes in simultaneous pancreas-kidney (SPK) transplantation. In an attempt to obtain a low rejection rate without antibody induction therapy, we undertook a prospective study of combined tacrolimus and mycophenolate mofetil and steroids as primary immunosuppression for SPK transplantation. In this study, we analyzed 17 patients who received low-dose intravenous tacrolimus as induction therapy. This was combined with oral tacrolimus, mycophenolate mofetil, and steroids as the primary immunosuppression regimen. There was a significant reduction of empirically and biopsy-proven rejection with an incidence of 23% (4 patients). Leukopenia, gastroparesis, and gastrointestinal side-effects were the cause of discontinuation of mycophenolate mofetil, or low tacrolimus trough level in those patients who developed rejection. All rejection episodes were easy to treat, and none of them required antibody therapy. The combination of tacrolimus with mycophenolate mofetil without antibody induction therapy is effective in preventing early acute rejection. This combination is safe and effective as an alternative immunosuppressive regimen after SPK transplantation.

Adult↗

Perioperative nursing and animal-assisted therapy.

Interacting with animals has been shown to reduce blood pressure and cholesterol, decrease anxiety, and improve a person's sense of well being. Animal-assisted therapy (AAT) can be incorporated into the care of perioperative patients. Some of the goals that can be met by using trained and certified therapy animals are reducing stress preoperatively, motivating patients to have a positive attitude, promoting postoperative activity, and reducing the need for pain medication. Infection control, immunosuppressed patients, and research are issues regarding AAT in the hospital setting that must be covered by policy and procedure. Suggestions for setting up an AAT program are discussed.

Animals↗