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Biomedical subjects

J Miller

Publications and source records attributed to J Miller.

At least 451 records · Page 25Linked to original sources

Urethritis/dysuria after simultaneous pancreas-kidney transplantation.

We evaluated the role of conservative treatment for urethritis and its complications after simultaneous pancreas-kidney (SPK) transplant. Twenty-six type I diabetic recipients with end-stage renal disease underwent SPK transplants with bladder exocrine drainage. Urethritis/ dysuria occurred in 4/26 (16%) of the patients. All cases resolved with conservative treatment that included Foley catheter and/or suprapubic cystostomy. Despite the frequency of this urological complication, none of the patients needed diversion of the exocrine drainage from the bladder to the intestine.

Adult↗

The influence of depression on physician-patient interaction in primary care.

BACKGROUND: Depression is common but not well diagnosed in primary care medicine. This study examines the influence of depression and its recognition on the physician-patient encounter. METHODS: A total of 508 new adult patients were assigned randomly to 105 primary care providers. Self-reported depression was determined by the Beck Depression Inventory (BDI) on entry to the study. Initial visits were videotaped and analyzed using the Davis Observation Code. Chart notes were reviewed for diagnosis of depression. RESULTS: Seventy-seven of the 508 study patients (15%) were identified as depressed in chart notes, while 130 patients (26%) had a BDI score > or = 9, indicating moderate to severe depression. Recognition of depression was associated with increased counseling, decreased time conducting physical examination, and an increase in overall visit length. Both elevated BDI scores and physician recognition of depression were associated with decreases in chatting. Failure to recognize depression was associated with increased time taking medical history. CONCLUSIONS: Results support the potential value of psychological screening instruments in primary care and provide information for training physicians in the recognition and management of depression. The content of office visits is different when patients are depressed or are diagnosed as depressed.

Adult↗

Transurethral laser therapy and urinary tract infections.

To date transurethral laser ablation of the prostate (TULAP) in benign prostatic hyperplasia (BPH) is the commonest form of transurethral laser surgery. The invention of the so-called "sidefire" laser fibre was the prerequisite condition for effective transurethral laser ablation of the prostate. Since the first transurethral laser ablation in human BPH was performed by Costello in September 1990, a multitude of urologists have adopted this technique. In the meantime, a great many studies have been carried out and a lot of data have been published. The initial, to some extent euphoric, enthusiasm of some urologists as well as some patients, especially in the USA and Europe, has turned into a more critical reflection. There is no doubt at all that TULAP is a feasible alternative treatment method with reasonable results. Especially in the high-risk patient, there is neither severe blood loss nor an uptake of irrigation fluid. It is also beneficial to allow unlimited treatment in patients on anticoagulant medication. Nevertheless, the value of TULAP in comparison to transurethral electroresection of the prostate (TURP), generally accepted as the "gold-standard" in the surgical therapy of BPH, remains unclear. A final assessment will only be possible when further data on mortality, short and long term morbidity and outcome with this method have been presented. Strong evidence exists that the operation can be performed without blood loss and uptake of irrigation fluid. A further advantage seems to be preservation of sexual function, especially anterograde ejaculation in the majority of patients, in comparison to the "gold-standard" TURP. In most studies, the value of TULAP is further compared with regard to the elimination of obstruction by means of pressure-flow-studies. The aspect most frequently neglected by all investigators to date is the frequency and severity of urinary tract infections (UTI) in patients in whom TULAP is performed. Basically, UTI in the form of cystitis, ascending infections such as male adnexitis or pyelonephritis, prostatitis of the remaining parts of the prostate and catheter-induced urethritis are associated with transurethral surgery in general. Certain data indicate an age-related frequency of UTI. From a rate of approximately 1% of UTI in infants, the frequency rises to 30% in the 8th decade of life. According to these data, one can expect that in a study of TULAP in high risk patients, most of whom are elderly, a large number present for surgery with a preexisting UTI. Other data demonstrate that after 4.5 days 50% and more of patients with an indwelling catheter develop an ascending UTI, although a closed urinary drainage system has been used. In most cases enterobacteriaceae, in 80% Escherichia coli, are detected. Especially in TULAP, a period of prolonged catheterisation has to be expected in the majority of patients. The risk of UTI in the perioperative phase is therefore expected to be higher. There are several higher risks and possibilities of complications in transurethral surgery in patients with UTI. Taking this into account, all our patients routinely undergo low dose antibiotic prophylactic treatment. The frequency of infections of the remaining parts of the prostate after prostatic surgery is strongly correlated to the flow characteristics in the prostatic urethra and to the amount of destruction of the prostatic tissue. Here are further reasons for a higher risk of infection after TULAP. Due to the fact that the prostatic tissue is not removed by a clear cut, but coagulated by laser beam, a rough surface due to tissue necrosis results. This is an ideal culture medium for bacteria aggravated by the disturbed laminar flow in the prostatic urethra, which favours an intraprostatic reflux of infected urine. There is evidence that UTI are the most important factor of morbidity during the first weeks after TULAP because of their bothersome symptoms.(ABSTRACT TRUNCATED)

Aged↗

Risk factors for the development of obliterative bronchiolitis after lung transplantation.

BACKGROUND: Acute rejection has emerged as an important risk factor for obliterative bronchiolitis after lung transplantation. We performed a multivariate analysis to assess the impact of additional variables. METHODS: Seventy-four recipients (48 heart-lung, 18 single-lung, and 8 bilateral-lung recipients) who survived longer than 90 days and underwent transplantation more than 15 months before data analysis were included in this study. Several variables were entered into a Cox regression analysis to determine their association with the development of bronchiolitis obliterans syndrome. RESULTS: Bronchiolitis obliterans syndrome developed in 48 (65%) of 74 patients. Significant correlations were detected for acute rejection score, defined as the sum of pathologic grades of each separate acute rejection episode (p = 0.0004, likelihood ratio test value = 12.4) and for lymphocytic bronchiolitis (p = 0.03). In a bivariate model, episodes of organizing pneumonia and bacterial or fungal pneumonia significantly increased the likelihood ratio test value of the acute rejection score. The addition of the cytomegalovirus infection score, reflecting the frequency and severity of infection, to the combination of the acute rejection score and episodes of bacterial or fungal pneumonia resulted in a further significant increase in the likelihood ratio test value. Significant risk factors for moderate to severe stages of airflow limitation were at least one episode of acute rejection of grade > or = 2, younger recipient age, and any acute rejection episode 180 days or longer after transplantation. CONCLUSIONS: Increasing frequency and severity of acute rejection episodes are strongly associated with the development of bronchiolitis obliterans syndrome. Lymphocytic bronchiolitis appeared to be significant by univariate analysis, but in a two-risk factor model, it did not augment the influence of acute rejection. Organizing pneumonia, bacterial or fungal pneumonia, and increasing severity and frequency of cytomegalovirus infections potentiate the effect of acute rejection. Late episodes of acute rejection and younger recipient age increase the risk for development of advanced disease.

Adolescent↗

Effects of particle size and number on the plasma clearance of chylomicrons and remnants.

Lymph chylomicrons of different sizes are known to be cleared at different rates, but the underlying mechanism for this effect has not been resolved. To investigate the differences in clearance rates between small and large particles, chylomicron-like lipid emulsions labeled with radioactive triolein and cholesteryl oleate were injected into conscious rats. The clearance from plasma of small emulsion particles was significantly slower than large when equal lipid masses of small and large particles were injected. Similar results were obtained in clearance studies with lymph chylomicrons. When equal numbers of either small or large emulsion particles were injected into rats, the clearance of the triolein label from large particles was significantly slower than small particles but no significant difference was found in the clearance of the remnants (traced by the cholesteryl oleate label) derived from small and large particles. However, when increased numbers of either small or large particles were injected, the clearances of emulsion triolein and remnants were significantly decreased. Larger particles were found to be lipolyzed significantly less than small. Simultaneous injections showed competition for removal of large and small particles, suggesting competition for a common, saturable removal process. Our findings provide evidence that particle number and size are determinants of the rates of plasma clearance of the triglyceride-rich lipoproteins and the results are consistent with a saturable process. Our data also show that particle number is more important than size and higher numbers of particles markedly affect the clearance of triglyceride-rich lipoproteins. However particle uptake by the liver is not sensitive to remnant size.

Animals↗

A clinical project to reduce confusion in hospitalized, older adults.

An innovative program to reduce confusion in elderly hospitalized patients was implemented and evaluated for use by staff nurses as part of their usual care activities. Four categories of environmental optimization interventions (EOI) were developed. Attention to factors in the hospital environment that fostered or inhibited implementation of the interventions by the EOI nurses made the program beneficial to patients and nurses.

Activities of Daily Living↗

Late infections after allogeneic bone marrow transplantations: comparison of incidence in related and unrelated donor transplant recipients.

Infectious complications are a major cause of morbidity and mortality after allogeneic bone marrow transplantation (BMT). We have evaluated the incidence of late infections (beyond day +50) in recipients of related (RD) and unrelated donor (URD) allogeneic BMT, factors associated with increased risks of infection, and the impact of the late infections on survival. Between 1989 and 1991, 249 patients received an RD (n = 151) or URD (n = 98) allogeneic BMT at the University of Minnesota and all late infections were investigated. Three hundred sixty-seven late infectious events developed in 162 patients between 50 days and 2 years after BMT. The incidence of any late infection was greater in URD versus RD recipients (84.7% v 68.2%, respectively; P = .009). In multivariate analysis, advanced graft-versus-host disease (GVHD) was significantly associated with late infections. The effect of GVHD was apparent only in RD recipients (relative risk [RR], 2.29; P = .003), whereas URD recipients, with or without GVHD, had more late infections compared with RD recipients without GVHD. Multivariate analysis showed that late posttransplantation infections were the dominant independent factor associated with increased nonrelapse mortality (RR, 5.5; P = .0001), resulting in improved 3-year survival for RD versus URD recipients (49.9% +/- 8% v 34.4% +/- 10%; P = .004). In this study, we observed that late infections are more frequent in URD recipients, resulting in substantially higher nonrelapse mortality. This prolonged period of increased infectious risk in URD recipients suggests the need for aggressive surveillance and therapy of late infections and perhaps prolonged antibiotic prophylaxis for all URD BMT recipients.

Adolescent↗

BPV E1 protein alters the kinetics of cell cycle entry of serum starved mouse fibroblasts.

A stable bovine papillomavirus E1 expressing cell line (C2E1) was used to investigate the effects of E1 protein on the requirement for growth factors during serum-induced reentry from quiescence to proliferation. Flow cytometric bivariate DNA/PCNA analysis was utilized to study the expression of proliferating cell nuclear antigen (PCNA) concomitant with this transition. C2E1 cells, unlike the control cells (CNEO), were able to reenter the cell cycle when stimulated with low serum (1%). Stimulation with 10% serum revealed that C2E1 cells entered the first cell cycle faster than CNEO, indicating that E1 protein decreased the time of progression from G0 stage upon serum activation. It was also shown that PCNA expression started earlier in C2E1 cells than in CNEO cells after quiescent cells were stimulated with 10% serum. Addition of 1% serum was able to induce PCNA expression in C2E1 but not in CNEO cells in the first 24 h after stimulation. Using Triton X-100 treatment, it was found that the distribution between bound and unbound forms of PCNA was altered in E1-expressing cells compared to CNEO cells. Based on these results, it is suggested that E1 might possess mitogen-like properties.

Animals↗

Intercellular adhesion molecule-1 dimerization and its consequences for adhesion mediated by lymphocyte function associated-1.

Intercellular adhesion molecule-1 (ICAM-1, CD54) is a ligand for the integrins lymphocyte function associated-1 (LFA-1, CD11a/CD18) and complement receptor-3 (Mac-1, CD11b/CD18) making it an important participant in many immune and inflammatory processes. Modified recombinant soluble ICAM-1 formed dimers. This result indicated that the ectodomain of ICAM-1 contains homophilic interaction sites. Soluble ICAM-1 dimers bind to solid-phase purified LFA-1 with high avidity (dissociation constant [Kd] = 8 nM) in contrast to soluble ICAM-1 monomers whose binding was not measurable. Cell surface ICAM-1 was found to be dimeric based on two distinct criteria. First, a monoclonal antibody specific for monomeric soluble ICAM-1, CA7, binds normal ICAM-1 poorly at the cell surface; this antibody, however, binds strongly to two mutant forms of ICAM-1 when expressed at the cell surface, thus identifying elements required for dimer formation. Second, chemical cross-linking of cell surface ICAM-1 on transfected cells and tumor necrosis factor-activated endothelial cells results in conversion of a portion of ICAM-1 to a covalent dimer. Cell surface ICAM-1 dimers are more potent ligands for LFA-1-dependent adhesion than ICAM-1 monomers. While many extracellular matrix-associated ligands of integrins are multimeric, this is the first evidence of specific, functionally important homodimerization of a cell surface integrin ligand.

Animals↗

Proteolysis of major histocompatibility complex class II-associated invariant chain is regulated by the alternatively spliced gene product, p41.

Invariant chain (Ii) is an intracellular type II transmembrane glycoprotein that is associated with major histocompatibility complex class II molecules during biosynthesis. Ii exists in two alternatively spliced forms, p31 and p41. Both p31 and p41 facilitate folding of class II molecules, promote egress from the endoplasmic reticulum, prevent premature peptide binding, and enhance localization to proteolytic endosomal compartments that are thought to be the sites for Ii degradation, antigen processing, and class II-peptide association. In spite of the dramatic and apparently equivalent effects that p31 and p41 have on class II biosynthesis, the ability of invariant chain to enhance antigen presentation to T cells is mostly restricted to p41. Here we show that degradation of Ii leads to the generation of a 12-kDa amino-terminal fragment that in p41-positive, but not in p31-positive, cells remains associated with class II molecules for an extended time. Interestingly, we find that coexpression of the two isoforms results in a change in the pattern of p31 degradation such that endosomal processing of p31 also leads to extended association of a similar 12-kDa fragment with class II molecules. These data raise the possibility that p41 may have the ability to impart its pattern of proteolytic processing on p31 molecules expressed in the same cells. This would enable a small number of p41 molecules to modify the post-translational transport and/or processing of an entire cohort of class II-Ii complexes in a manner that could account for the unique ability of p41 to enhance antigen presentation.

Alternative Splicing↗

Invariant chain-independent antigen presentation depends primarily upon the pool of newly synthesized MHC class II molecules.

During biosynthesis, MHC class II molecules are diverted to endocytic compartments in which they bind antigenic peptides to be displayed on the surfaces of APC. For many Ags, the efficiency of class II presentation is enhanced by the intracellular association of class II with invariant chain (li), consistent with a role for newly synthesized class II molecules in Ag presentation. For a subset of Ags, however, efficient presentation does not require li. These Ags may also be bound by class II molecules en route to the cell surface. Alternatively, li-independent Ag presentation may utilize a pool of preexisting class II molecules that may gain access to endosomes following internalization from the cell surface. To examine the role of newly synthesized class II in the presentation of the li-independent Ag, RNase, we placed class II biosynthesis under the translational control of an iron response element. Chelation of iron from the media resulted in efficient diminution of class II synthesis and a marked decrease in the efficiency of RNase presentation. When compared with other cells expressing varying amounts of class II, we found that the ability to present RNase correlates with the level of class II biosynthesis and not with the level of class II surface expression. Because these cells internalize class II at a significant rate, we conclude that even in the absence of li, class II molecules can reach endocytic compartments containing antigenic peptides and they do so on their biosynthetic pathway.

Antigen Presentation↗