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Biomedical subjects

R A Miller

Publications and source records attributed to R A Miller.

At least 163 records · Page 9Linked to original sources
PubMed1996

Modeling principles for QMR medical findings.

Structured representation of medical information is essential for ensuring the accuracy and reliability of computerized decision support applications. Such systems require input that is error-free and clinically pertinent. This paper reviews existing medical models, particularly those exploited for natural language understanding, and highlights modeling features important to future indexing of medical texts with controlled vocabularies. A hybrid representation derived from existing frame-based and conceptual-graph-based systems is proposed to represent relevant medical terms as used by experts.

Abstracting and Indexing↗
PubMed1996

A new approach to the implementation of direct care-provider order entry.

Successful implementation of direct computer-based care-provider order entry traditionally relies on one of two different approaches development from scratch or installation of a commercial product. The former requires extensive resources; the latter, by its proprietary nature, limits extension of the system beyond capabilities supplied by the vendor. This paper describes an intermediate approach using the association of a locally-developed and controlled set of distributed microcomputer based applications and a commercial, mainframe-based order entry application used as an order transaction processing system. This combination provides both an intuitive user interface and a platform for implementing clinical decision-support tools.

Computer Communication Networks↗
PubMed1995

CrmA, a poxvirus-encoded serpin, inhibits cytotoxic T-lymphocyte-mediated apoptosis.

Cytotoxic T-lymphocytes (CTLs), by virtue of their ability to recognize and induce apoptotic death of virus-infected cells, comprise a major antiviral defense mechanism. The induction of apoptosis by CTLs can be completely accounted for by two mechanisms: (i) a Ca(2+)-dependent component that involves the exocytotic release of serine proteases known as granzymes from CTL granules and their subsequent insertion into the target cell to induce apoptosis and (ii) a Ca(2+)-independent component that involves the activation of Fas, a receptor on the target cell membrane that triggers apoptosis. Although viruses have evolved several indirect mechanisms for evading the CTL response, direct inhibition of the apoptotic cascade has never been described. We now show for the first time that the cowpox virus protein CrmA, a protease inhibitor of the serpin family, is capable of inhibiting CTL-mediated cytolysis. The inhibitory effect is largely the result of blockade of the Ca(2+)-independent (i.e. Fas-mediated) component of CTL killing. CrmA thus represents the first example of a viral gene product capable of directly blocking CTL-mediated cell death.

Apoptosis↗
PubMed1995

Rapid tyrosine phosphorylation of Grb2 and Shc in T cells exposed to anti-CD3, anti-CD4, and anti-CD45 stimuli: differential effects of aging.

Two adapter proteins, Grb2 and Shc, have recently been implicated in the transmission of activation signals from the stimulated T cell receptor to Ras. We show here that in vitro stimulation of mouse splenic T cells with crosslinked anti-CD3 antibody leads within 30 s to phosphorylation of both Grb2 and Shc. Treatment with crosslinked anti-CD45 antibody leads to phosphorylation of Grb2 and also to a slight retardation in the mobility of this protein in an SDS polyacrylamide gel; both changes are seen within 30 s of crosslinking. Crosslinked anti-CD4 antibody leads to phosphorylation of Shc and to the phosphorylation of a 30-kDa protein that cross-reacts with anti-Grb2 antibodies. Aging leads to a decline in CD3-stimulated phosphorylation of Shc (but not Grb2), and to an increase in CD4-stimulated phosphorylation of Grb2, Shc, and the 30-kDa Grb2-like protein. Increased tyrosine-phosphorylation of Grb2 after exposure to either anti-CD3 or anti-CD45 suggests that Grb2 may be a common substrate for both CD3-linked kinases and the CD45 phosphatase. The differences between T cells from young and old mice suggest that aging may lead to a set of alterations in kinase/substrate coupling that contribute to immune dysfunction in the elderly, and that activation of the Ras pathway might be impaired by aging in T lymphocytes.

Adaptor Proteins, Signal Transducing↗
PubMed1995

Antagonistic interactions among T cell subsets of old mice revealed by limiting dilution analysis.

When CD4 spleen cells from old (but not young) mice are tested for Con A-induced proliferation in limiting dilution assays, the dose response curve shows a nonlinear relationship. We interpret these observations using a two-cell model, in which proliferation of one cell type (LPC1) can be blocked by a second cell type (LPC2), which can itself generate detectable proliferation only at high multiplicities. The two-cell model accounts for several observations: 1) the variation in curve shape as a function of incubation time; 2) the skewed distribution of wells scored as "negative" in cultures of old splenocytes; and 3) the initially antagonistic effects of old splenocytes titrated into cultures containing fixed numbers of young responders. To provide a further test of the two-cell model, ionomycin-resistant (CaR) and ionomycin-sensitive (CaS) cells were separated using a Percoll/ionomycin gradient. The CaR preparation, shown previously to consist largely of memory T cells, showed the dose curve predicted for the LPC2 cell type, whereas the CaS (naive) cells showed the single-hit kinetics postulated for LPC1 cells. Furthermore, mixtures of CaR and CaS cells from young mice reproduced the zigzag dose curve characteristically produced by unseparated cells from old mice. These data suggest that the spleens of both young and old mice contain two kinds of Con A-responsive CD4 cell: one that proliferates vigorously, and a second, calcium ionophore-resistant type that proliferates less well, that can interfere with proliferation of the first cell type, and whose frequency increases with age.

Aging↗
PubMed1995

Long-term toxicity studies of ozone in F344/N rats and B6C3F1 mice.

The toxicity and carcinogenicity of ozone was evaluated in Fischer 344/N rats and B6C3F1 mice exposed to 0, 0.12 (2 years only), 0.5 or 1.0 ppm ozone by inhalation for 2-year and lifetime exposures. A 2-year cocarcinogenicity study (male rats only) included the subcutaneous administration of 0, 0.1 or 1.0 mg/kg/body wt. of 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) for the first 20 weeks along with inhalation exposure to 0 or 0.5 ppm ozone followed by additional 84 weeks of ozone exposure alone. Ozone exposure in rats did not cause an increased incidence of lung neoplasms. In the cocarcinogenicity study, ozone exposure did not have an additive carcinogenic effect. Lifetime and 2-year ozone exposure was associated with a marginal increase in lung tumors in male B6C3F1 mice and a more pronounced increase in females. Unique mutations in the K-ras gene were found in the mouse lung neoplasms from the ozone-exposed mice.

Animals↗
PubMed1995

Lupus erythematosus-like oral mucosal and skin lesions in a carrier of chronic granulomatous disease. Chronic granulomatous disease carrier genodermatosis.

We present a case of a young female patient who for 8 years was believed to have discoid lupus erythematosus of the skin and oral mucosae. Only after her infant son had a near-fatal pulmonary infection was the diagnosis of chronic granulomatous disease made and her lupus erythematosus-like mucocutaneous lesions recognized as manifestations of her carrier status for chronic granulomatous disease. The purpose of this report is to raise awareness of and better characterize the mucocutaneous manifestations of carriers of chronic granulomatous disease. Early identification of carriers permits genetic counseling and prenatal diagnosis and forewarns pediatricians so that they can provide better care for affected infants.

Adult↗
PubMed1995

Leptotrichia buccalis bacteremia in patients treated in a single bone marrow transplant unit.

We describe four cases of bacteremia due to Leptotrichia buccalis (an organism that is part of the normal human oral flora) that occurred in a bone marrow transplant unit over a 3-month period. All of the patients were neutropenic, all had mucositis or esophagitis, and all were receiving antimicrobial prophylaxis with ciprofloxacin and vancomycin (drugs to which Leptotrichia is resistant). One patient died of adult respiratory distress syndrome; the others had minimal symptoms. Pulsed field gel electrophoresis of bacterial DNA digested with Sma 1 demonstrated a unique banding pattern for each isolate, indicating that the isolates belonged to distinct strains. Quantitative gas-liquid chromatography of whole-cell free fatty acids confirmed the uniqueness of the strains, obviating the need to search for a common source of infection. We postulate that this outbreak resulted from antibiotic selection pressure on the oral flora in patients who had been compromised by severe neutropenia and mucosal disruption.

Adult↗
PubMed1995

Urological day case surgery in elderly and medically unfit patients using sedoanalgesia: what are the limits?

OBJECTIVE: To assess how elderly and medically unfit patients cope with day case surgery in a urological unit using sedoanalgesia. PATIENTS AND METHODS: One hundred patients (mean age 78 years, range 59-97) either over the age of 75 years, or with an American Society of Anesthesiologists (ASA) status of 3 or 4 (58 patients) were studied before and after surgery to assess their medical condition, home circumstances and how they coped with their first day after the operation. RESULTS: Ninety patients found the procedure good or acceptable and 86 thought having their operation and going home on the same day was a good idea. CONCLUSION: Elderly and medically unfit patients can be treated safely with no serious complications using sedoanalgesia in a well organized Day Unit equipped with full monitoring facilities.

Adaptation, Psychological↗
PubMed1995

Are transrectal ultrasonically guided biopsies required for the accurate diagnosis of carcinoma of the prostate? Can digitally guided systematic biopsies offer an acceptable alternative?

OBJECTIVE: To compare the diagnostic yield of ultrasonically guided and digitally guided systematic biopsies of the prostate. PATIENTS AND METHODS: Fifty two patients with suspected but unproven carcinoma of the prostate underwent simultaneous transrectal ultrasonography (TRUS)-guided and digitally guided systematic biopsies of the prostate. A mean of 12 cores was obtained from each patient. On average more cores were obtained with TRUS guidance (mean 6.7) than with digital guidance (mean 5.3). RESULTS: Cancer was detected in 19 patients and the diagnosis was made by both techniques in 16. Two patients had tumour detected only with TRUS guidance and one only with digital guidance. No complications occurred. CONCLUSION: This study indicates that there is no significant difference between TRUS guidance and digital guidance to direct systematic biopsies of the prostate. The use of routine TRUS in screening programmes is now in doubt.

Aged↗
PubMed1995

Mycobacterium tuberculosis in lung transplant recipients.

The diagnosis and treatment of Mycobacterium tuberculosis, although difficult in normal hosts, are even more complex in transplant recipients. As a result of the use of immunosuppressive agents, transplant recipients are not only predisposed to primary tuberculous infections, but they are also uniquely at risk for reactivation of latent infection acquired prior to transplantation or transmitted via the donor organ. The diagnosis of pulmonary tuberculosis can be even more elusive in the setting of lung transplantation where other pulmonary complications can make diagnosis difficult. Here we report a case of a patient who died of disseminated M. tuberculosis 12 wk after lung transplantation, and we review tuberculous infections in lung transplant recipients.

Bronchoalveolar Lavage Fluid↗
PubMed1995

Protease-cleaved iron-transferrin augments oxidant-mediated endothelial cell injury via hydroxyl radical formation.

Previous work has shown that the Pseudomonas-derived protease, pseudomonas elastase (PAE), can modify transferrin to form iron complexes capable of catalyzing the formation of hydroxyl radical (.OH) from neutrophil (PMN)-derived superoxide (.O2-) and hydrogen peroxide (H2O2). As the lung is a major site of Pseudomonas infection, the ability of these iron chelates to augment oxidant-mediated pulmonary artery endothelial cell injury via release of 51Cr from prelabeled cells was examined. Diferrictransferrin previously cleaved with PAE significantly enhanced porcine pulmonary artery endothelial cell monolayer injury from 2.3-6.3 to 15.8-17.0% of maximum, resulting from exposure to H2O2, products of the xanthine/xanthine oxidase reaction, or PMA-stimulated PMNs. Iron associated with transferrin appeared to be responsible for cell injury. Spin trapping and the formation of thiobarbituric acid-reactive 2-deoxyribose oxidation products demonstrated the production of .OH in this system. The addition of catalase, dimethyl thiourea, and the hydrophobic spin trap, alpha-phenyl-n-terbutyl-nitrone, offered significant protection from injury (27.8-58.2%). Since sites of Pseudomonas infection contain other proteases, the ability of porcine pancreatic elastase and trypsin to substitute for PAE was examined. Results were similar to those observed with PAE. We conclude .OH formation resulting from protease alteration of transferrin may serve as a mechanism of tissue injury at sites of bacterial infection and other processes characterized by increased proteolytic activity.

Animals↗
PubMed1995

Determination of in vitro metatarsocuneiform pressure before and after surgical modification of the great toe.

In vitro contact pressures were measured at the first metatarsocuneiform joint in order to determine the effect of resectional arthroplasty and arthrodesis of the metatarsophalangeal joint of the great toe. Eight fresh cadaver feet were loaded with the Instron machine to determine the pressure seen at the first metatarsocuneiform joint. The specimens were subsequently modified by performing either an arthrodesis of the great toe metatarsophalangeal joint or an arthroplasty of this joint by removal of the proximal one third of the proximal phalanx. A second test was then performed. Pressure-sensitive film was analyzed to determine maximum pressure and total transmitted force. No significant pressure change was seen after the arthrodesis. After the resection arthroplasty, there was a significant decrease in both the maximum pressure and the total force measured at the first metatarsocuneiform joint.

Adult↗