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Biomedical subjects

R L Miller

Publications and source records attributed to R L Miller.

At least 91 records · Page 5Linked to original sources
PubMed1994

Can we afford to do cardiac operations in 1996? A risk-reward curve for cardiac surgery.

Parsonnet risk estimates and postoperative lengths of stay were studied for two cohorts of cardiac surgical patients. The first cohort consisted of 287 patients and was taken from 1984, the first full year of this cardiac surgical program. The second cohort consisted of all 1,167 patients operated on in the calendar years 1989 to 1991. We found that the mean risk for the patients had nearly doubled in this interval and that the risk distribution changed significantly from one skewed toward good-risk patients to a nearly uniform distribution through all risk categories. A high correlation was identified (0.9761) between the postoperative length of stay and the mean risk estimates for the 1989 to 1991 cohort of patients. This permits a regression equation to be calculated showing that the length of stay could be estimated at 7.06 days + 0.21 times the mean risk for a patient or cohort of patients. This relationship is then used to develop a relationship between the net income for a given case or cohort of patients and the length of stay or risk. These data suggest that, in most hospitals, hospital fixed costs are a major determinant, even more so than daily charges, of the relationship between the hospital's finances and the mean risks of patients undertaken in the cardiac surgical program. The consequences of this are discussed.

Algorithms↗
PubMed1994

Emergency department use of radiology services at a large urban teaching hospital.

RATIONALE AND OBJECTIVES: Little research has explored the use of radiologic services by emergency departments and the factors that influence use. This study aimed to identify and characterize these factors. METHODS: A total of 13,228 consecutive patient emergency charts from a large university emergency department were reviewed, and multiple parameters were entered into a database. The database was studied and statistical testing was done to identify significant parameters for patients who required imaging studies (X-ray group) and those who did not (non-X-ray group). RESULTS: Factors such as age, diagnosis, urgency of illness, and illness severe enough to require hospitalization were statistically significant in determining the need for a radiologic evaluation in the emergency setting. When these factors were equalized for the X-ray and non-X-ray groups by multivariate linear regression analysis, male sex was also found to be statistically significant. Factors such as race and presence or absence of health insurance were not statistically influential on multivariate analysis. CONCLUSIONS: Older age, diagnosis, and factors related to severity of illness affected the use of radiologic services in the emergency setting. Sex differences were also detected.

Adolescent↗
PubMed1994

Posttherapy suppression of genital herpes simplex virus (HSV) recurrences and enhancement of HSV-specific T-cell memory by imiquimod in guinea pigs.

Imiquimod, an immunomodulator with no direct in vitro antiviral activity, has in vivo anti-herpesvirus activity by inducing interferon and enhancing other only partially defined immune responses. Imiquimod treatment of primary genital herpes simplex virus (HSV) infection in guinea pigs reduces the level of genital disease by 90%. We further investigated its utility as suppressive therapy of recurrent disease in animals that had recently recovered from primary genital HSV-2 disease. Imiquimod administered intravaginally once per day for 5 days reduced the number of recurrences only during treatment, while a 21-day regimen reduced the number of recurrences for 8 weeks. For the entire 10 weeks of observation, overall numbers of recurrences were reduced 67% by the 21-day imiquimod treatment (P < 0.0001). Latent HSV in ganglia was not affected by either regimen. Increased circulating alpha interferon activity was observed during therapy with both regimens. Interferon levels rapidly returned to baseline with cessation of treatment. Posttreatment, 5-day imiquimod treatment did not provide clinical benefit or enhancement of cell-mediated or cytokine responses. Twenty-one-day imiquimod treatment reduced both the number of clinical recurrences and levels of HSV antibody for 5 to 6 weeks posttreatment compared with the placebo. Additionally, 21-day imiquimod treatment enhanced HSV antigen-specific interleukin 2 production and proliferative responses by mononuclear cells (P < 0.001) for 4 weeks after treatment. Twenty-one-day imiquimod therapy suppressed recurrent HSV genital disease during and for weeks after therapy, enhanced memory-dependent cytokine and T-cell responses, and reduced the level of antibody responses.

Adjuvants, Immunologic↗
PubMed1993

Chain terminator sequencing of double-stranded DNA with built-in error correction.

Chain terminator sequencing is usually performed on single-stranded DNA. We propose a technique to determine a DNA sequence by sequencing both strands of a double strand in two four-lane gels. The first set of four lanes will contain a superposition of sequence information from the two complementary strands. The second set of four lanes will contain a different superposition in which one of the two single strands is "shifted" relative to the other. This technique provides redundant information sufficient for error correction--not just the error detection achieved by the standard approach of separately sequencing a single strand and its complement. The information content per four-lane gel is more than 50% higher in this double-stranded approach. Using this technique, the number of chain sequencings--including chain syntheses and gel separations--required to achieve a desired level of accuracy can be reduced by up to a factor of two. Unlike the ordinary single-stranded sequencing, some analysis is required to obtain the single-stranded sequence information from the double-stranded data, particularly in the presence of sequencing errors. This analysis and a computer simulation of double-stranded sequencing in the presence of errors are presented.

Animals↗
PubMed1993

Expression of a mouse-channel catfish chimeric IgM molecule in a mouse myeloma cell.

Fusion genes encoding a murine VH domain and the constant region domains of the mu chain from the channel catfish, Ictalurus punctatus, were stably expressed in the lambda light chain producing mouse myeloma cell line J558L. Although the pathways of pre-mRNA processing for expression of membrane (micron and secreted (microsecond) forms of the mu chain differ between mammals and teleosts, mRNAs encoding both catfish micron and microsecond were correctly expressed in the mouse myeloma cells. The mouse-channel catfish chimeric mu chain polypeptide was able to associate covalently with the mouse lambda light chain and assemble, intracellularly, into polymers of covalent structure (microL)2-8 which resembled those seen with native catfish IgM. In contrast to native catfish IgM, the mouse-catfish chimeric IgM showed the property of binding strongly to protein A of Staphylococcus aureus. The mouse-channel catfish chimeric IgM was core-glycosylated, but did not contain terminal sialic acid. Secretion rates for the chimeric IgM were low, and the possibility could not be excluded that extracellular chimeric IgM was released from dead or dying cells. The reason(s) for the intracellular retention of the chimeric IgM (probably in the endoplasmic reticulum) are not known, but those mechanisms involving retention via cysteine residues were excluded.

Animals↗
PubMed1993

Effects of therapy with an immunomodulator (imiquimod, R-837) alone and with acyclovir on genital HSV-2 infection in guinea-pigs when begun after lesion development.

We evaluated the effects of the immunomodulator, imiquimod (R-837) applied topically, alone and in combination with i.p. acyclovir (ACV) on acute, recurrent and neural HSV-2 genital infection in guinea-pigs when 10 days of therapy was begun after HSV lesions developed. The combined therapy was most effective, significantly reducing the severity of the acute disease, as early as 2 days (P < 0.05), and vaginal viral shedding (P < 0.05) as early as 1 day after therapy was begun. The total lesion score for the acute disease was also significantly less in the group receiving imiquimod and ACV (5.4 +/- 0.5) compared to controls (13.1 +/- 1.2, P < 0.001) or imiquimod alone (9.8 +/- 1.2, P < 0.05). Therapy, however, had no significant effect on the number of days with recurrent lesions. Imiquimod increased the lymphoproliferative response to HSV (P < 0.01), while combined therapy reduced HSV antibody titers (P < 0.01) on day 28 compared to placebo and also reduced the effect of imiquimod alone on the lymphoproliferative response. The combination of this effective immunomodulator, imiquimod, and acyclovir appears to provide effective therapy for acute genital HSV-2 infection even when begun after lesion development.

Acute Disease↗
PubMed1993

Evaluation of population pharmacokinetics in therapeutic trials. IV. Application to postmarketing surveillance.

The feasibility of incorporating blood sampling for population pharmacokinetic analysis into postmarketing surveillance was evaluated. Demographic and drug disposition data, consisting of two blood samples collected at a random time during two different dose intervals, was prospectively collected for 94 psychiatric inpatients (mean age, 48 +/- 13 years) receiving alprazolam. Mixed-effect modeling was used to estimate population pharmacokinetic parameters. The mean alprazolam clearance, volume of distribution, and absorption rate constant were 0.05 L/hr/kg, 0.7 L/kg, and 1.1 hr-1, respectively. Clearance was increased by 59% in women, decreased by 26% in patients with multiple organ disease, and decreased by 23% in patients older than 60 years of age. These estimates are similar to those determined from rigorous premarketing clinical trials. Interindividual variability in alprazolam clearance was relatively small (40%) after adjustment for significant patient covariates. Population pharmacokinetic analysis represents a reasonable approach to assessment of pharmacokinetic variability in a large, heterogenous patient population.

Adult↗
PubMed1993

Adjuvant effects of imiquimod on a herpes simplex virus type 2 glycoprotein vaccine in guinea pigs.

The adjuvant effects of imiquimod for a herpes simplex virus (HSV) vaccine were evaluated. Guinea pigs were immunized with 35 micrograms of lectin-purified HSV-2 glycoproteins 14 and 35 days before intravaginal HSV-2 inoculation. Immunizations were given either alone, with complete Freund's adjuvant, or with three different 5-day regimens of imiquimod. Although immunization alone decreased the severity of the acute disease and viral replication, in two separate experiments, the addition of imiquimod produced further decreases. The addition of subcutaneous imiquimod further decreased viral shedding by > 3 logs on day 1 after virus inoculation (P < .001). All groups that received immunization and imiquimod also developed significantly fewer HSV recurrent lesion days (P < .05-.001) compared to immunization alone. No recurrent lesions were detected in the group that received immunization and subcutaneous imiquimod. Imiquimod enhanced the effectiveness of HSV-2 immunization, especially in reducing recurrent HSV disease, and should be evaluated further as an adjuvant.

Acute Disease↗
PubMed1993

Treatment of aggressive children with clonidine: results of an open pilot study.

Seventeen aggressive children (14 boys and 3 girls) aged 5 to 15 years, who were characterized by cruel behavior to others and destruction of property, entered an open pilot study using clonidine to evaluate its efficacy and safety and drug-induced changes in plasma gamma aminobutyric acid (GABA). Aggression decreased in 15 children with minimal side effects. In five cases, GABA increased from 105.4 +/- 15.2 ng/mL at baseline to 125.2 +/- 10.8 ng/mL at follow-up (p < 0.01). A sixth patient was noncompliant. These findings suggest that GABA may be correlated with childhood aggressiveness and may be a useful marker of drug compliance. Pharmacotherapy with clonidine should be further assessed for the control of aggression.

Adolescent↗
PubMed1993

The Yale Geriatric Care Program: a model of care to prevent functional decline in hospitalized elderly patients.

OBJECTIVE: To describe the structure and implementation of the Yale Geriatric Care Program, an innovative, nursing-centered model for developing geriatric nursing expertise throughout an acute-care hospital. DESIGN: Descriptive study of an intervention in a prospective cohort of patients. SETTING: University teaching hospital. PATIENTS: Two hundred forty four patients aged 70 years and older on four non-intensive care intervention units during the study period (July 9, 1990 to July 31, 1991). INTERVENTION: The Geriatric Care Program involved an integrated model of primary nurses, specially trained unit-based geriatric resource nurses, gerontological nurse specialists, and geriatric physicians. The intervention included surveillance and identification of frail older patients, unit-based geriatric educational programs for all nurses, special education and support for the geriatric resource nurses, and twice-weekly rounds of the Geriatric Care Team. RESULTS: The Geriatric Care Program has been successfully implemented on four units. The interventions ranged from general clarification of goals in 226 (92%) to specific recommendations for management of immobility in 100 (41%), bladder/bowel problems in 99 (41%), pressure ulcer treatment or prevention in 61 (25%), confusion evaluation or management in 62 (25%), and adjustment of medications in 43 (18%). Overall, 68% of the specific recommendations were documented to have been implemented. Barriers to implementation of the program have included initial difficulties with recruitment and retainment of geriatric resource nurses (due to high nursing turnover and the increased time commitment required), breakdown in communication and carryover of recommendations between nursing shifts, and obstacles to communication between the nursing and medical staff. CONCLUSIONS: An innovative model of care, in which geriatric nursing was integrated as part of standard nursing care on selected medical and surgical units, has been designed and implemented. Evaluation of the effectiveness and costs of this intervention are currently underway.

Activities of Daily Living↗
PubMed1992

Phosphorylation of carbovir enantiomers by cellular enzymes determines the stereoselectivity of antiviral activity.

Two enantiomers of carbovir, a carbocyclic analog of 2',3'-dideoxyguanosine, were compared with respect to their phosphorylation and the phosphorylation of their nucleotides by mammalian enzymes. 5'-Nucleotidase catalyzed the phosphorylation of (-)-carbovir, which is active against HIV (human immunodeficiency virus), but did not phosphorylate (+)-carbovir. (-)-Carbovir monophosphate was 7,000 times more efficient as a substrate for GMP kinase than was (+)-carbovir monophosphate. Pyruvate kinase, phosphoglycerate kinase, and creatine kinase phosphorylated both enantiomers of carbovir diphosphate at similar rates. Nucleoside-diphosphate kinase preferentially phosphorylated the (-)-enantiomer. Both enantiomers of carbovir triphosphate were substrates and alternative substrate inhibitors of HIV reverse transcriptase. Thus, the contrasting HIV-inhibitory activities of carbovir enantiomers were due to differential phosphorylation by cellular enzymes and not due to enantioselectivity of HIV reverse transcriptase.

Antiviral Agents↗
PubMed1992

Cinnamon-induced stomatitis venenata, Clinical and characteristic histopathologic features.

Fourteen new cases of cinnamon-induced stomatitis are reported. Ten of these fourteen cases were first detected on the basis of histopathologic changes, which included hyperkeratosis, chronic lichenoid mucositis with plasmacytic infiltration, and marked chronic perivasculitis. Six cases of false-positive histopathologic findings are presented for comparison. It is recommended that when the histopathologic features described are recognized, cinnamon stomatitis should be considered.

Adult↗
PubMed1992

Delusions and behavioral disturbances in cognitively impaired elderly persons.

OBJECTIVE: To compare cognitive function and the prevalence of selected behavioral problems in delusional and non-delusional dementia patients. DESIGN: Retrospective medical record review. SETTING: An outpatient geriatric assessment center. PARTICIPANTS: 114 consecutive patients with dementia. MAIN OUTCOME MEASURES: Delusions as recorded in a consultation report. RESULTS: Delusions were described in 25.5% of patients. A variety of behavioral disturbances were more common in delusional than non-delusional patients, including agitation, angry or hostile outbursts, urinary incontinence, wandering or pacing, and insomnia. While cognitive function as measured by the MMSE was similar in delusional and non-delusional patients (18.9 +/- 3.8 and 19.2 +/- 5.9, respectively), there was a statistically borderline tendency for delusions to occur more often in patients in the mid-range of cognitive impairment (17 less than or equal to MMSE less than or equal to 23) compared with patients with greater or lesser degrees of cognitive impairment (32% vs 17% respectively). CONCLUSION: Delusions in dementia are associated with a variety of behavioral problems. Further studies are needed to clarify the role of delusions in the development of disruptive behaviors in dementing illness.

Aged↗
PubMed1991

Determination of cocaine, benzoylecgonine and ecgonine methyl ester in plasma by reversed-phase high-performance liquid chromatography.

A combined assay is described for cocaine and its major metabolites, benzoylecgonine and ecgonine methyl ester. The method uses electrochemical and ultraviolet detectors in series. A non-silica column is used with high-pH mobile phase. The three compounds are completely separated from other cocaine metabolites. The assay has been suitable for pharmacokinetic studies of cocaine disposition in animal studies.

Animals↗
PubMed1991

Purification and characterization of 5'-deoxy-5'-methylthioadenosine (MTA) phosphorylase from human liver.

5'-Methylthioadenosine phosphorylase was purified 8000-fold from human liver using a combination of affinity chromatography, chromatofocusing and gel filtration. A 25% overall yield was obtained. The specific activity of the final preparation was 40 mumol of 5'-methylthioadenosine cleaved per hr per mg of protein. The enzyme had an apparent molecular weight of 55,000 daltons, as determined by gel filtration of Superose 12 and Sephadex G-150, with a subunit molecular weight of 30,000 daltons, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The substrate specificity of the purified enzyme was studied in both the direction of nucleoside cleavage and nucleoside synthesis.

Chromatography, Gel↗