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Biomedical subjects

M D Miller

Publications and source records attributed to M D Miller.

At least 145 records · Page 8Linked to original sources

Theoretical infrared spectra of some model polycyclic aromatic hydrocarbons: effect of ionization.

In order to test the hypothesis of ionized polycyclic aromatic hydrocarbons (PAHs) as possible carriers of the UIR bands, we realized a computational exploration on selected PAHs of small dimension in order to identify which changes ionization would induce on their IR spectra. In this study we performed ab initio calculations of the spectra of neutral and positively ionized naphthalene, anthracene, and pyrene. The results are significantly important. The frequencies in the cations are slightly shifted with respect to the neutral species, but no general conclusion can be reached from the three molecules considered. By contrast, the relative intensities of most vibrations are strongly affected by ionization, leading to a much better agreement between the calculated CH/CC vibration intensity ratios and those deduced from observations.

Anthracenes↗

Simian immunodeficiency virus-specific cytotoxic T lymphocytes in rhesus monkeys: characterization and vaccine induction.

An effective HIV vaccine should be capable of eliciting virus-specific cytotoxic T lymphocytes (CTL). We have characterized the cellular and molecular features of a simian immunodeficiency virus of macaques (SIVmac) gag-specific CTL response in rhesus monkeys. We have shown that SIVmac-infected rhesus monkeys expressing the major histocompatibility complex (MHC) class I molecule Mamu-A*01 develop a SIVmac gag-specific CTL response which recognizes a 9 amino acid fragment of the gag protein in association with Mamu-A*01. Moreover, this peptide/MHC class I recognition is mediated by T cell receptors (TCR) employing a predominant V beta gene family and J beta gene. Using this understanding of a SIVmac-specific CTL response, we have shown that SIVmac-specific CTL can be elicited through three novel approaches to vaccination: a recombinant viral vector, a recombinant bacterial vector and a peptide vaccine. These studies illustrate the utility of the SIV/macaque model in AIDS vaccine research.

Animals↗

The arthroscopic "impingement test" during anterior cruciate ligament reconstruction.

A primary goal of ACL reconstruction is to avoid graft impingement, which may lead to loss of motion and/or an increased incidence of instability. Although surgeons are cognizant of this potential problem, the intraoperative correction of graft impingement is technically demanding because the graft-notch relationship is obscured by the trochlea articulating with the tibial plateau during the final 10 degrees of extension. We present a simple impingement test that is performed before graft insertion and fixation to help avoid this potential pitfall.

Anterior Cruciate Ligament↗

Posterior sacroiliac fixation using a sacral pedicle targeting device: an anatomical study.

This study compares the accuracy of posterior sacroiliac (SI) screw placement using a "free-hand" method, without the use of fluoroscopy, versus a specially developed targeting device. Posterior SI screws were inserted after exposing the iliac wing in five cadavers on one side, and inserted percutaneously with a unique targeting device on the opposite side. Fluoroscopy was not used for screw or pedicle placement on either side. Computed tomography and dissection results were then used to grade screw placement for both sides. A statistically significant difference between the sides was found. More importantly, three screws on the free-hand side violated major neurovascular structures. The regional anatomy was defined: structures most at risk are the iliac vein ventrally and the sacral canal dorsally. A highly variable "safe zone" (mean arc 43 degrees at the S1 level and 30 degrees at the S2 level) was established. Inclination of the SI joint was also defined (mean 29 degrees at the S1 level and 17 degrees at the S2 level). SI screw placement using the specially developed targeting device is technically less demanding, requires less soft tissue dissection, allows variable placement, and poses minimal risk to major neurovascular structures. Our limited clinical experience with the device is encouraging. The potential application of this technique to unstable vertical shear fractures is appealing.

Bone Screws↗

Ventilator-assisted youth: appraisal and nursing care.

An interdisciplinary review of 16 ventilator-assisted, cervical-cord injured youth, aged 3-19 years, was completed to explore long-term outcomes and develop recommendations for care. Ten youths were younger than 12 years; 6 were adolescents. The mean initial hospital length of stay was 192 days. Discharged youths were followed for 1-73 months after hospitalization. Nursing implications were developed using a systems approach with North American Nursing Diagnosis Association (NANDA) approved diagnoses. Nursing case management was used to coordinate discharge planning and continuity of care. At the time of data collection 13 youths had been successfully reintegrated to home, school and community, the least restrictive environments for all.

Adolescent↗

Simian immunodeficiency virus-specific CD8+ lymphocyte response in acutely infected rhesus monkeys.

To assess the possible role of cytotoxic T lymphocytes (CTLs) in containing the spread of human immunodeficiency virus in acutely infected individuals, the temporal evolution of the virus-specific CD8+ lymphocyte response was defined in simian immunodeficiency virus of macaques (SIVmac)-infected rhesus monkeys. A brief period of SIVmac plasma antigenemia was seen 9 to 16 days following intravenous infection with SIVmac, ending as the absolute number of CD8+ peripheral blood lymphocytes (PBLs) increased. In a prospective assessment of the ability of CD8+ lymphocytes of these monkeys to suppress SIVmac replication in autologous PBLs, inhibitory activity was detected as early as 4 days, with a more pronounced effect 12 to 16 days following infection. SIVmac Gag- and Nef-specific CD8+ effector cell activities were demonstrable in PBLs of animals by 2 weeks following virus inoculation. In fact, SIVmac-specific CTL precursors were documented in the PBLs of rhesus monkeys 4 to 6 days after SIVmac infection. These studies indicate that AIDS virus-specific CD8+ CTLs are present in PBLs within days of infection and may play an important role in containing the early spread of virus.

Acute Disease↗

Partial agonism by gastrin for a cholecystokinin receptor mediating pepsinogen secretion.

Isolated gastric glands from rabbit were used to characterize the functional cholecystokinin (CCK)-like peptide receptors that mediate pepsinogen secretion. Pepsinogen secretion was stimulated by both CCK octapeptide sulfate (CCK-8) and A-71378, a selective CCK-A-type receptor agonist, with similar mean effective doses (1.0 and 0.8 nM, respectively). Compared with CCK-8, gastrin-17 (G-17-I) showed reduced potency and only partial efficacy for stimulation of pepsinogen secretion while inhibiting the maximal CCK-8-stimulated response. The nonpeptide inhibitors, asperlicin and L-364,718, inhibited pepsinogen secretion with identical pA2 values for antagonism of both CCK and gastrin, indicating that both peptides interact with the same functional receptor. Specific binding of [3H]CCK-8 to isolated chief cell membranes was displaced fully by both CCK and gastrin, indicating full receptor occupancy by both peptides. A novel synthetic peptide analogue, pseudogastrin [(Glu)5-Ala-Tyr-Nle-Gly-Trp-Nle-Asp-Phe-NH2], was used to investigate the structural basis for the lower potency and efficacy of G-17-I. The potency of CCK and gastrin analogues for pepsinogen secretion was found to be dependent on both sulfation of a tyrosine residue and the position of the tyrosine residue relative to the COOH-terminal phenylalanine amide. The efficacy appears to be determined partially by the extended NH2-terminal sequence of G-17-I. The results of the present study are interpreted to show that pepsinogen secretion is mediated by a CCK-A-type receptor and gastrin acts at the same receptor as a partial agonist.

Amino Acid Sequence↗

Posterior cruciate ligament injuries.

Posterior cruciate ligament (PCL) injuries are more common than has been previously reported. Recent clinical and basic science studies have helped define the important functional anatomy and biomechanics of this "forgotten" ligament and have raised questions regarding the reported benign natural history of isolated tears of the PCL. While recent technical advancements in the application of magnetic resonance imaging to knee ligament injuries may assist in identifying PCL tears, the posterior drawer test remains the "gold standard" for diagnosis. Numerous treatment options have been proposed, but anatomical reconstructions have yielded consistently good clinical results. A review of our current knowledge of the basic science and clinical studies on the posterior cruciate ligament is presented to stimulate further interest and research in this exciting area.

Acute Disease↗

The role of osteotomy in the anterior cruciate ligament-deficient knee.

Whether the ACL-deficient knee actually causes osteoarthritis is unclear. What is clear is that the two conditions can exist simultaneously. Treatment of these patients must be individualized based on their activities, symptoms, and findings. In the unusual patient with significant instability and moderate medial compartment osteoarthritis, a combined valgus osteotomy and ACL reconstruction may be appropriate. The authors emphasize that this is a salvage procedure, not intended to return the athlete to competition. Although the short-term results are promising, the long-term results of this treatment are unknown.

Animals↗

The use of allograft. Techniques and results.

There are several advantages to allograft use for ACL reconstruction. Bone-patella, tendon-bone, and achilles tendon allografts are routinely used. The one-incision endoscopic technique is described. Very few comparative studies exist in the current literature, but clinical results with allograft tissues appear to be similar to those of autograft use.

Animals↗

Clinical decision-making following abnormal Papanicolaou smear reports.

OBJECTIVE: Interpretation of abnormal Papanicolaou smear reports and the subsequent management of the patient frequently present significant decision-making problems for clinicians. The purpose of this study was to evaluate family physician clinical decision-making strategies for abnormal cervical cytology reports using simulation techniques. METHODS: One hundred fifteen practicing family physicians evaluated two simulations of women with abnormal cervical cytology, the first with inflammatory cytology and the second with a high-grade squamous intraepithelial lesion. RESULTS: Most physicians (66%) selected an etiology evaluation and specific treatment approach to an inflammatory report, while 26% of respondents chose empiric treatment. For the high-grade squamous intraepithelial lesion simulation, 88% of physicians chose the appropriate management response of colposcopic evaluation. CONCLUSIONS: Practice experience, level of involvement, clinician gender, and type of cervical cytology classification influenced family physician clinical decision-making. The majority of responses to an inflammatory or high-grade squamous intraepithelial lesion report was appropriate based on current scientific data.

Adult↗

Physician attitudes toward the Bethesda System of reporting cervical cytology.

OBJECTIVE: The purpose of this investigation was to determine family physicians' and gynecologists' attitudes toward and understanding of the Bethesda System, a new cervical cytology classification and reporting system. METHODS: A convenience sample of 159 family physicians and gynecologists completed a questionnaire that assessed attitudes, knowledge, and opinions about the Bethesda System. RESULTS: Compared with family physicians, gynecologists thought the Bethesda System was more likely to cause patient management problems (p < 0.001) and preferred not to combine viral cytologic effects with mild dysplasia when reporting a low-grade squamous intraepithelial lesion (p < 0.004). However, increased understanding of the system by physicians correlated with greater preference for the Bethesda System (p < 0.02). In this exploratory study, family physicians, rather than gynecologists, were more inclined to use the Bethesda System and perceived it as a means to reduce clinical evaluation and patient management problems. Gynecologists reported a fuller understanding of the Bethesda System, yet they were more critical of the cytology categorizations. Within each specialty, greater understanding of the Bethesda System led to its wider acceptance.

Adult↗

Criteria for evaluating performance of third-year medical students.

BACKGROUND: Evaluating medical student performance in clinical settings is an aspect of teaching that educators sometimes find difficult. This study was conducted to determine evaluation criteria for clinical performance that were considered important by physician faculty. These criteria were subsequently used in the student evaluation process for a decentralized clerkship in family medicine. METHODS: In Phase I, physician faculty were surveyed to identify preferred criteria for evaluating student performance through an open-ended format. In Phase II, the identified items were refined. In Phase III, 45 items were presented to the faculty for rating importance on a visual analogue scale. RESULTS: Twenty-nine of 31 physicians responded. Factor analysis identified three factors that accounted for 76.6% of the variance: application of knowledge, relationship with patients, and therapeutics in family medicine. CONCLUSIONS: Results of the study suggest that physician faculty have internalized expectations of clinical competence in the discipline of family medicine that address the basic dimensions of cognitive ability, problem-solving skills, and interpersonal relationships.

Clinical Competence↗

Colposcopic accuracy in a residency training program: defining competency and proficiency.

BACKGROUND: The determination of proficiency in procedural skills has evoked keen interest, but meaningful guidelines are limited by the absence of pertinent clinical data. Colposcopic accuracy is defined as the clinical correlation between a colposcopic impression and a histologic report. The colposcopic accuracy of physicians in a university-based family practice residency colposcopy program was evaluated. METHODS: Demographic information, clinical findings, and laboratory results of patients evaluated by colposcopy were prospectively recorded. Colposcopic accuracy was calculated based on the agreement of the colposcopic impression with the histologic interpretation within one histologic grade. RESULTS: Colposcopic examinations were performed on 282 patients. Histologic evidence of premalignant cervical disease was identified in 115 patients as follows: mild dysplasia, 72; moderate dysplasia, 24; and severe dysplasia, 19. The colposcopic impression agreed within one histologic grade in 188 of 205 patients for a colposcopic accuracy rate of 91.7% (95% CI = 87.1% to 95.1%). CONCLUSIONS: Given an acceptable latitude of clinical correlation between the colposcopic impression and histologic interpretation, the colposcopic accuracy of family physicians compared favorably with that reported by other colposcopists. The more common colposcopic errors were overestimation of low-grade disease and underestimation of high-grade disease. Colposcopic accuracy at an essential minimal proficiency level of 80% should form the basis for assessing specialized perceptual ability and therefore determining colposcopic competency.

Adolescent↗

Measurement of subjective phenomena in primary care research: the Visual Analogue Scale.

The visual analogue scale is a technique used to measure subjective phenomena. It is a self-reporting device consisting of a line of predetermined length that separates extreme boundaries of the phenomenon being measured. The purpose of this review is to report on the characteristics of the visual analogue scale technique, including its reliability, validity, accuracy, and scale value. This review presents several examples of the usefulness of the visual analogue scale technique in primary care research projects, describes its advantages and limitations, and presents suggestions for constructing visual analogue scales.

Affect↗

Cytotoxic T lymphocytes do not appear to select for mutations in an immunodominant epitope of simian immunodeficiency virus gag.

Studies to date assessing HIV escape from CTL in vivo have yielded conflicting results. Previous studies have demonstrated that simian immunodeficiency virus of macaques (SIVmac)-infected rhesus monkeys expressing the MHC class I allele Mamu-A*01 reproducibly develop a gag-specific CTL response limited to a 9-amino acid epitope of the SIVmac gag protein (residues 182-190 within peptide 11C). To determine whether CTL have a role in selecting for AIDS virus mutants, we examined mutations in SIVmac proviral DNA encoding this gag CTL epitope in PBL of infected rhesus monkeys. Three Mamu-A*01+ rhesus monkeys were infected with SIVmac and assessed for gag- and peptide 11C-specific CTL responses. This specific CTL response was maintained in two monkeys, but lost in the third animal 2 yr after infection. The generation of proviral gag mutations was then determined by sequencing 500-bp proviral fragments amplified from fresh PBL obtained from the monkeys more than 2.5 yr after infection. Although numerous point mutations were characterized in 131 polymerase chain reaction-generated clones of SIVmac gag, only four mutations within the gag CTL epitope-coding region of the genome were identified. Comparison of synonymous and nonsynonymous nucleotide substitutions in the regions encoding peptide 11C (p11C) and the flanking gag protein indicated a lack of selective pressure for viral mutations in the CTL epitope coding region. Interestingly, a predominant gag mutant encoding a single amino acid change in p11C was found in a monkey which lost its CTL activity. However, even in this setting there was no evidence for selection of mutations in the CTL epitope coding region when compared with the flanking region. Furthermore, synthetic peptides corresponding to all naturally occurring variants in the gag epitope-coding region were recognized by cloned and bulk cultured effector cells of the infected monkeys with persistent CTL. These results indicate that SIVmac gag- and p11C-specific CTL do not select for mutations in the immunodominant epitope-coding region and that the naturally occurring mutants do not appear to escape CTL recognition.

Amino Acid Sequence↗