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Biomedical subjects

R L Miller

Publications and source records attributed to R L Miller.

At least 55 records · Page 3Linked to original sources
PubMed1998

What is the marginal cost for marginal risk in cardiac surgery?

BACKGROUND: It has been shown that postoperative length of stay (LOS) correlates highly with mortality risk for cardiac surgical procedures. Similar correlations have been found for charges with LOS and costs with risk. METHODS: Postoperative LOS and risk scores were obtained, tabulated, and compiled into the five original Parsonnet risk groups for 2,589 patients who underwent cardiac operations from 1992 through 1996 at one hospital. The correlation of the group mean LOS with the group mean risk was tested. RESULTS: The correlation coefficient was 0.9827; 96.58% of the variance was removed using risk to predict LOS. A calculation of the difference in cost for difference in risk for cohorts of patients is developed. CONCLUSIONS: The high correlation of mean LOS with mean risk permits calculation of marginal cost for marginal risk based on clinical data. The marginal cost is equal to the difference in variable costs for cohorts.

Aged↗
PubMed1998

Hypoxia regulates endothelin-1 production by the inner medullary collecting duct.

Renal endothelin-1 (ET-1 ) production is increased by hypoxia and has been implicated in ischemia-induced renal hypoperfusion. Because the inner medullary collecting duct (IMCD) is a major source of ET- 1 in the kidney, and because ET- 1--in the setting of ischemic renal failure-may alter medullary perfusion, we sought to determine whether hypoxia modulated ET-1 production by IMCD cells. Primary cultures of rat IMCD cells were exposed to 21%, 3%, or 0%O2. IMCD ET-1 secretion significantly increased after exposure of cultures to 3% O2 (114.1% +/- 4.7% increase over control value) and 0%O2 (171.7% +/- 7.9% increase). ET-1 mRNA levels, as determined by reverse transcription-polymerase chain reaction, also increased 2.5-fold after 24-hour exposure to 0% O2. We speculate that a hypoxia-induced increase in IMCD ET-1 production plays a role in modulating renal medullary perfusion during ischemic renal failure.

Animals↗
PubMed1998

Analysis of cytokine signaling in patients with extrinsic asthma and hyperimmunoglobulin E.

BACKGROUND: Recent data suggest that the regulation of class switching to IgE by cytokines is mediated by STAT transcription factors. The induction of IgE by IL-4 and IL-13 occurs through the activation of the intracellular signal-transducing protein Stat6, whereas the inhibition of IgE class switching by interferon-y (IFN-gamma) occurs through the activation of Statl. OBJECTIVE: We hypothesized that in extrinsic asthma or in cases of markedly elevated IgE (ie, hyperimmunoglobulin E [HIE]) increased levels of IgE may be associated with alterations in the cytokine levels or the activation of Stat6. METHODS: PBMCs and sera from 8 patients with extrinsic asthma (mean IgE, 285+/-100 IU/mL), 3 patients with HIE (mean IgE, 7050+/-1122 IU/mL), and 14 nonatopic control subjects (mean IgE, 112+/-28 IU/mL) were analyzed. RESULTS: The mean IL-4 level detected by ELISA was much greater in patients with HIE than control subjects (88.6+/-11.5 pg/mL vs 11.5+/-7.1 pg/mL, P = .005), and increased IL-4 levels among patients with both asthma and HIE correlated with the increased IgE levels. In contrast, IL-13 levels were not elevated. Levels of Stat6 protein present in PBMCs did not differ in the patients and control subjects. Examination of Stat6 DNA-binding activity demonstrated no activation of IL-4 signaling in patients with either HIE or acute asthma. Interestingly, evidence for the presence of B cells that have already switched to IgE was seen in PBMCs of several patients with asthma or HIE. CONCLUSION: These results indicate that (1) IgE production in asthma and HIE usually is associated with elevated levels of IL-4, but not IL-13, in the peripheral blood; (2) the increased sera IL-4 levels in asthma and HIE are not sufficient to induce Stat6 activation in PBMCs; and (3) evidence of switch recombination to epsilon may be detected in isolated cases of elevated IgE. This implies that high levels of IgE in these patients either results from B cells that have already undergone class switching, from Ig class switching that is localized to target tissues, or both.

Adult↗
PubMed1998

Frequency-shaped amplification changes the neural representation of speech with noise-induced hearing loss.

Temporal response patterns of single auditory nerve fibers were used to characterize the effects of a common hearing-aid processing scheme, frequency-shaped amplification, on the encoding of the vowel /epsilon/ in cats with a permanent noise-induced hearing loss. These responses were contrasted with responses to unmodified stimuli in control and impaired cats. Noise-induced hearing loss leads to a degraded representation of the formant frequencies, in which strong phase locking to the formants is not observed in fibers with best frequencies (BFs) near the formants and there is a wide spread of formant phase locking to fibers with higher BFs (Miller et al., 1997a,b). Frequency shaping effectively limits the upward spread of locking to F1, which improves the representation of higher frequency components of the vowel. However, it also increases phase locking to harmonics in the trough between the formants, which decreases the contrast between F1 and the trough in the neural representation. Moreover, it does not prevent the spread to higher BFs of responses to the second and third formants. The results show a beneficial effect of frequency shaping, but also show that interactions between particular gain functions and particular spectral shapes can result in unwanted distortions of the neural representation of the signal.

Acoustic Stimulation↗
PubMed1998

Effects of high sound levels on responses to the vowel "eh" in cat auditory nerve.

The vowel "eh" was used to study auditory-nerve responses at high sound levels (60-110 dB). By changing the playback sampling rate of the stimulus, the second formant (F2) frequency was set at best frequency (BF) for fibers with BFs between 1 and 3 kHz. For vowel stimuli, auditory-nerve fibers tend to phase-lock to the formant component nearest the fiber's BF. The responses of fibers with BFs near F2 are captured by the F2 component, meaning that fibers respond as if the stimulus consisted only of the F2 component. These narrowband responses are seen up to levels of 80-100 dB, above which a response to F1 emerges. The F1 response grows, at the expense of the F2 response, and is dominant at the highest levels. The level at which the F1 response appears is BF dependent and is higher at lower BFs. This effect appears to be suppression of the F2 response by F1. At levels near 100 dB, a component 1/component 2 transition is observed. All components of the vowel undergo the transition simultaneously, as judged by the 180 degrees phase inversion that occurs at the C2 transition. Above the C2 threshold, a broadband response to many components of the vowel is observed. These results demonstrate that the neural representation of speech in normal ears is degraded at high sound levels, such as those used in hearing aids.

Acoustic Stimulation↗
PubMed1998

HIV prevention with male prostitutes and patrons of hustler bars: replication of an HIV preventive intervention.

The core objectives of this study were to document the process by which a community-based organization replicated and adapted an experimentally developed intervention to its own use and to explore the effectiveness of that HIV prevention program for male prostitutes and other patrons in New York City "hustler" bars. The intervention model employed was based on previous research with gay men (Kelly, St. Lawrence, Diaz, et al., 1991; Kelly, St. Lawrence, Stevenson, et al., 1992) and inspired by diffusion of innovation theory (Rogers, 1995). The effects of the current intervention were assessed on a sample of 1,741 male prostitutes and bar patrons. Analyses indicated significant reductions in paid, unprotected sexual intercourse and oral sex following the intervention. Analyses further indicated that the data were partially consistent with the program's model, which specified that norms were the putative mediator of behavior change in the intervention. Also, the intervention's effects varied by bar and by participants' race/ethnicity. Data support the utility of the intervention model for an urban sample of men at high risk for HIV infection. The importance of exploring the mechanisms that underlie the intervention is discussed.

Adolescent↗
PubMed1998

Effects of a myofunctional appliance on orofacial muscle activity and structures.

The aim of the study was to examine the effect of an oral shield treatment on orofacial muscle activity and facial morphology in children with lip and/or tongue dysfunction. The sample consisted of 7 girls and 2 boys, 7 to 12 years old. EMG recordings with and without the shield in situ were obtained when the shield was placed, and 3, 6, and 12 months later. Lateral cephalograms were obtained at the initial and 1-year stages. The lip muscles showed dominant activity when the subjects were sucking on an empty straw and during swallowing; this was strongest during the first 3 months. The mentalis, buccinator, and digastric muscles generally showed weaker activity. The anterior temporal muscle showed dominant activity during maximal clench, but after the 3-month stage a significant decrease was noted. After 1 year of treatment, no significant changes in overjet or overbite were observed. Most of the craniofacial growth changes were normal for the age group. The results indicate that treatment with an oral shield caused a decrease in orofacial muscle activity during oral functions. Although there was a slight average retraction of the maxillary incisors, the change in position was not statistically significant.

Cephalometry↗
PubMed1998

Cytokine induction in hairless mouse and rat skin after topical application of the immune response modifiers imiquimod and S-28463.

ALDARA (imiquimod cream 5%) recently became available for the treatment of genital and perianal warts; however, the topical mechanism of action of imiquimod is not fully understood. Imiquimod, and its analogs R-842, S-27609, and S-28463, are potent anti-viral and anti-tumor agents in animal models. Much of the biologic activity of these compounds can be attributed to the induction of cytokines, including interferon-alpha, tumor necrosis factor-alpha, interleukins-1, -6, -8, and others. This study was performed to characterize the response of mice and rats to topical application of imiquimod and S-28463 and also to evaluate these agents in cultures of murine and human skin cells. Topical administration of imiquimod or S-28463 to the flanks of hairless mice and rats leads to increases in local concentrations of interferon and tumor necrosis factor in the skin. The concentrations of interferon and tumor necrosis factor were higher at the site of drug application than in skin from the contralateral flank or skin from untreated animals. Interferon-alpha mRNA levels were also elevated in the skin of mice after topical application of either imiquimod or S-28463. In vitro, both imiquimod and S-28463 induced increases in interferon and tumor necrosis factor in cultures of cells isolated from hairless mouse skin. Imiquimod also increased interleukin-8 concentrations in human keratinocyte and fibroblast cultures, whereas S-28463 induced increases in tumor necrosis factor in fibroblast cultures. These results demonstrate that imiquimod and S-28463 stimulate production of cytokines in the skin after topical application, which may play a major role in its activity in genital wart patients.

Adjuvants, Immunologic↗
PubMed1998

A randomized, controlled, molecular study of condylomata acuminata clearance during treatment with imiquimod.

Imiquimod, an immune response modifier, has been demonstrated to be safe and effective in the treatment of external genital and perianal warts caused by human papillomavirus (HPV). To identify the molecular mechanism(s) by which condylomata acuminata clear during topical treatment with imiquimod, wart skin biopsies were taken from patients before treatment, at treatment week 6, and at the end of treatment. Tissues were analyzed for HPV DNA and for mRNA of several cytokines and HPV gene products. Wart clearance was associated with evidence of tissue production of interferon-alpha, -beta, and -gamma and tumor necrosis factor-alpha. Regression of warts was strongly associated with a decrease in HPV DNA and in mRNA expression for both early and late viral proteins. Thus, topical imiquimod treatment of anogenital warts led to significant increases in local production of multiple interferon mRNAs and a significant reduction in virus load as measured by decreases in HPV DNA and mRNA for early HPV proteins.

Administration, Topical↗
PubMed1998

Attenuation of virus-induced airway dysfunction in rats treated with imiquimod.

Viral respiratory infections cause acute airway abnormalities consisting of inflammation and physiological dysfunction in both animals and humans. It is likely that inflammatory cell products, such as cytokines, contribute substantially to viral-induced airway dysfunction. We hypothesized that imiquimod, an immune response enhancing agent that induces interferon-alpha, would attenuate the development of airway dysfunction during acute viral illness in rats. Adult Brown Norway rats were inoculated with parainfluenza type 1 (Sendai) virus or sterile vehicle, and treated with either imiquimod or water. Respiratory system resistance (Rrs), arterial oxygen tension (Pa,O2), lung viral titres and bronchoalveolar lavage (BAL) leucocyte counts were measured in anaesthetized, paralysed, ventilated rats. Virus-infected, water-treated rats had a significant decrease in Pa,O2 and had significant increases in leucocyte count and Rrs when compared to both the virus-infected, imiquimod-treated, (Pa,O2, p = 0.03; leucocyte count, p = 0.02; and Rrs, p = 0.009) and noninfected, water-treated rats (Pa,O2, p = 0.007; leucocyte count, p = 0.001; and Rrs, p = 0.01). In addition, imiquimod suppressed BAL eosinophils in both virus-infected (p = 0.02) and noninfected (p = 0.001) groups, and lowered overall virus titres (p = 0.03). Thus, both virus-induced airway inflammation and physiological dysfunction were attenuated significantly by imiquimod treatment in this animal model. By further delineating mechanisms by which infections induce airway dysfunction in animal models, more specific pharmacological interventions can be developed for the treatment of virus-induced asthma.

Adjuvants, Immunologic↗
PubMed1998

Association between right ventricular function and perfusion abnormalities in hemodynamically stable patients with acute pulmonary embolism.

BACKGROUND/OBJECTIVES: Patients presenting with acute pulmonary embolism associated with hemodynamic compromise exhibit right ventricular enlargement and dysfunction on transthoracic echocardiogram. However, the degree of echocardiographic abnormalities among hemodynamically stable patients without preexisting cardiopulmonary disease during the acute stage of pulmonary embolism, and following treatment, is unknown. Therefore, this study was designed to assess the extent of right ventricular abnormalities detected on transthoracic echocardiogram in patients following acute pulmonary embolism and during treatment with anticoagulation or vena caval interruption. The extent of pulmonary vascular obstruction and complication rate on follow-up were also assessed. DESIGN/INTERVENTIONS: Sixty-four consecutive hemodynamically stable patients without preexisting known cardiopulmonary disorder presenting with acute pulmonary embolism and undergoing treatment with anticoagulation or inferior vena caval interruption were studied. All subjects underwent a two-dimensional transthoracic echocardiogram within 24 h of diagnosis. The degree of perfusion abnormality on lung scan was quantified. Twenty-six patients underwent follow-up echocardiogram and lung scan at 6 weeks. The echocardiographic findings were compared with those obtained from a group of normal control subjects matched for gender and age. RESULTS: Although the mean right ventricular end-diastolic areas did not differ (21.9+/-5.2 cm2 vs 20.1+/-2.9 cm2 for control subjects; p=not significant), the right ventricular end-systolic area was larger in comparison to our series of control subjects (14.6+/-5.1 cm2 vs 11.7+/-2.0 cm2; p=0.025). Fractional right ventricular area change was reduced in the patient group compared with the control subjects (34.3+/-9.0% vs 41.3+/-7.0%; p=0.003). The extent of right ventricular end-systolic area enlargement and decrease in fractional area change did not correlate with the degree of pulmonary vascular obstruction. Patients who were restudied at 6 weeks showed minimal improvement in echocardiographic findings, despite almost complete resolution of perfusion defects on lung scan. CONCLUSIONS: The extent of right ventricular dysfunction in hemodynamically stable, previously normal patients with acute pulmonary embolism does not reflect the extent of the perfusion abnormalities. Further, right ventricular enlargement and systolic dysfunction are present and persistent despite treatment with heparin and warfarin therapy or vena caval interruption.

Acute Disease↗
PubMed1998

Imiquimod 5% cream (Aldara).

Imiquimod is a novel synthetic molecule with potent immune-modifying activities. Formulated in a 5% vanishing cream as Aldara, this self-applied therapy has shown good efficacy and safety in the treatment of external genital and perianal warts caused by human papillomavirus (HPV) infection (Condyloma acuminata). The molecule does not demonstrate direct antiviral activity, but through induction of cytokines results in immune-based resolution of wart tissue and reduction of viral burden. Phase III trials of imiquimod have demonstrated that patients who experience complete clearance of either new or recalcitrant warts tend to remain clear, possibly related to Th1 immune recognition and memory. Self-application, good tolerability and a unique mechanism of action combine to make imiquimod a reasonable first-line therapy for genital warts. The effects of imiquimod on immune function suggest several potential uses. Preclinical studies of infection with herpes simplex virus (HSV), cutaneous leishmaniasis, Rift Valley Fever virus and vesiculostomatitis virus have shown reduced viral persistence, reduced recurrence (HSV) and diminished pathology (Leishmania donovani). In a murine tumour model using the FCB bladder cancer cell line, imiquimod behaves as a potent adjuvant leading to immune-based tumour cell eradication and immunity against subsequent FCB cell challenge. The ability of imiquimod to induce significant production of interferon alpha (IFN-alpha) by monocytes/macrophages suggests that diseases responsive to recombinant interferon therapy, such as basal cell carcinoma, may be reasonable clinical targets. The induction of tumour necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma) and interleukin-12 (IL-12) leads to inhibition of IL-5, with animal models demonstrating immune deviation away from Th2 immune responses. The observation that several patients with hepatitis C infection and eosinophilia showed normalisation of elevated eosinophil counts in association with oral imiquimod therapy encourages further exploration of the immune modifying properties of this novel molecule. This review is focused on the use of imiquimod for the treatment of external genital and perianal warts.

Journal Article↗
PubMed1997

The equivalent bronchodilator effects of salbutamol formulated in chlorofluorocarbon and hydrofluoroalkane-134a metered dose inhalers on the histamine-induced pulmonary response in dogs.

PURPOSE: The bronchodilator effect of salbutamol formulated in hydrofluoroalkane-134a (HFA-134a), a chlorofluorocarbon (CFC)-free propellant for metered dose inhalation (MDI) devices, was compared with that of salbutamol formulated in CFC in anesthetized dogs. METHODS: Bronchospasms were induced by the intravenous injection of histamine, and bronchial resistance was measured by the method of Konzett and Rossler. RESULTS: While the placebo vehicles (HFA-134a and CFC propellants) had no significant effect on histamine-induced bronchospasms, the salbutamol/HFA-134a and salbutamol/CFC MDI formulations had equivalent dose-related inhibitory effects. CONCLUSIONS: These data indicated that salbutamol formulated in HFA-134a and that in CFC propellant are bioequivalent.

Albuterol↗
PubMed1997

Effects of acoustic trauma on the representation of the vowel "eh" in cat auditory nerve fibers.

A population study of cat auditory-nerve fibers was used to characterize the permanent deficits induced by exposure to 110-115 dB SPL, narrow-band noise. Fibers in the region of acoustic trauma (roughly 1-6 kHz) showed a loss of sensitivity at best frequency (BF) of about 50-60 dB and an increased tuning bandwidth. A correlation between weakened two-tone suppression and loss of sensitivity was found for fibers with BFs above 1 kHz. Single-fiber responses to the vowel "eh" were recorded at intensities ranging from near threshold to a maximum of about 110 dB SPL. In normal cochleas, the temporal response patterns show a capture phenomenon, in which the first two formant frequencies dominate the responses at high sound levels among fibers with BFs near the formant frequencies. After acoustic trauma, fibers in the region of threshold shift synchronized to a broad range of the vowel's harmonics and thus did not show capture by the second formant at any sound level used. The broadband nature of this response is consistent with the broadened tuning observed in the damaged fibers, but may also reflect a weakening of compressive nonlinearities responsible for synchrony capture in the normal cochlea.

Animals↗
PubMed1996

Testicular microlithiasis: a benign condition with a malignant association.

Testicular microlithiasis (TM), which usually affects both testes, is diagnosed primarily by ultrasound. TM has been found to be associated with benign conditions but has also been reported in association with testicular cancer. Echographically, TM is manifested by diffuse, punctate, non-shadowing, hyperechoic foci within the testicular parenchyma. To date, more than 80 cases of TM have been documented sonographically or pathologically; 25 of them have demonstrated an association with pathologically proven testicular cancer (p < 0.05). Thirty-two cases were associated with infertility/subfertility (p < 0.05). We believe the finding of TM on ultrasound should heighten the radiologist's suspicion of testicular malignancy. If no malignancy is identified on initial evaluation including CT of the chest and abdomen, close clinical follow-up with periodic (every 6 to 12 months) scrotal ultrasound examination is probably indicated.

Adolescent↗