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Biomedical subjects

C A Miller

Publications and source records attributed to C A Miller.

At least 91 records · Page 5Linked to original sources
PubMed1995

Mechanical ventricular assistance: an economical and effective means of treating end-stage heart disease.

BACKGROUND: Heightened awareness of medical costs has escalated criticism toward expensive medical therapy. METHODS: The use of ventricular assistance devices (VADs) at Pennsylvania State University as a bridge to transplantation was reviewed. Records of 43 patients listed as status 1 from July 1991 to July 1994 were compared. RESULTS: This analysis demonstrated that for all patients treated with the intent to transplant, those who were bridged with a VAD exhibited a trend toward an improved transplantation rate (92% versus 68%) and a significantly greater rate of discharge from the hospital (92% versus 55.4%; p = 0.023) than the medically managed patients. Although overall charges and costs were higher in VAD-supported patients, this was related to significantly longer pretransplantation hospitalization. When normalized to daily costs and charges, this discrepancy in expenses was eliminated. CONCLUSIONS: The superior rate of discharge at equitable daily costs and charges for the VAD patients draws continued enthusiasm toward use of these devices as a bridge to transplantation. Furthermore, development of outpatient care for VAD-supported patients and continued advances in the use of these devices may further reduce the cost of managing these critically ill patients.

Adolescent↗
PubMed1995

Functional responses from guinea pigs with cochlear implants. I. Electrophysiological and psychophysical measures.

We examined electrophysiological and psychophysical measures of the electrically stimulated auditory system of guinea pigs implanted with chronic intracochlear electrodes. Guinea pigs were trained to detect low-level acoustic stimuli and then unilaterally deafened and implanted with one extracochlear and two intracochlear electrodes. Electrically evoked auditory brainstem responses (EABRs) and psychophysical detection thresholds were obtained from the same animals using pulsatile stimuli. Supplementary EABR data were obtained from additional, untrained, animals. Thresholds were obtained as a function of stimulus phase duration and monopolar and longitudinal-bipolar electrode configurations. The slopes of the EABR and psychophysical functions for bipolar stimulation, averaged across subjects within 1 month after implantation, were -5.25 and -6.18 dB per doubling of pulse duration, respectively. These slopes were obtained with pulse durations ranging from 20 to 400 microseconds/phase; slope was reduced at longer pulse durations. Strength-duration slope also varied as a function of electrode configuration: monopolar stimulation produced steeper functions than did bipolar stimulation. Differences between EABR and psychophysical strength-duration measures suggest the existence of central mechanisms of stimulus integration in addition to that occurring at the level of the auditory nerve. Differences observed with variation of stimulus parameters (e.g., monopolar vs. bipolar stimulation modes) suggest that the specific mode of intracochlear electrical stimulation can influence stimulus integration. Such observations may be useful in the design of prosthetic devices and furthering our understanding of electrical excitation of the auditory system.

Acoustic Stimulation↗
PubMed1995

Functional responses from guinea pigs with cochlear implants. II. Changes in electrophysiological and psychophysical measures over time.

This study, the second of a two-part investigation, assessed changes over time in functional measures of the electrically stimulated auditory system following ototoxic deafening. Guinea pigs were trained to respond behaviorally to threshold level acoustic stimuli and then unilaterally deafened and implanted with a bipolar pair of electrodes within the cochlea and a single extracochlear electrode. Using pulsatile stimuli, thresholds for the electrically evoked auditory brainstem response (EABR) and psychophysical detection were repeatedly collected from the same animals over 3-month post-implantation periods. Thresholds were obtained as a function of stimulus phase duration primarily using bipolar intracochlear stimulation. As in earlier studies, the threshold measures exhibited both intra- and intersubject variability. Analysis of group data failed to show any statistically significant changes over time in either EABR or psychophysical threshold at any fixed pulse duration. However, significant changes over time were found in the slopes of the strength-duration functions for both measures. Slopes became shallower with time, suggesting a reduction in the efficiency of stimulus current integration, a trend presumed to occur with neural degeneration. This result suggests that strength-duration functions could be useful as a clinical diagnostic measure.

Acoustic Stimulation↗
PubMed1995

p493F12 kinase: a novel MAP kinase expressed in a subset of neurons in the human nervous system.

Monoclonal antibody 3F12 identifies a cytoplasmic antigen of 49 kDa in human hippocampus and neocortex. The distribution of 3F12 immunoreactive neurons closely matches that of Alzheimer's disease (AD) targeted neurons in these areas. In some hippocampal neurons of AD patients, this antigen colocalizes with ALZ-50, indicating the presence of AD pathology in these neurons. Molecular characterization of the 3F12 cDNA revealed it to be a member of the MAP kinase family, showing 43% amino acid sequence identity to human extracellular related kinase 2 (p42mapk). We have confirmed that p493F12 kinase autophosphorylates both threonine and tyrosine residues, as expected for a MAP kinase. The p49 mRNA is expressed exclusively in the nervous system. In the brain, the distribution of these neurons closely corresponds to 3F12 antigen-bearing neurons. The p493F12 gene maps to the human chromosome 21q21 region, a region that may be important in the pathogenesis of AD and Down's syndrome.

Adult↗
PubMed1995

Carbonyl-related posttranslational modification of neurofilament protein in the neurofibrillary pathology of Alzheimer's disease.

We present the first evidence for carbonyl-related posttranslational modifications of neurofilaments in the neurofibrillary pathology of Alzheimer's disease (AD). Two distinct monoclonal antibodies that consistently labeled neurofibrillary tangles (NFTs), neuropil threads, and granulovacuolar degeneration in sections of AD tissue also labeled the neurofilaments within axons of the white matter following modification by reducing sugars, glutaraldehyde, formaldehyde, or malondialdehyde. The epitope recognized by these two antibodies shows a strict dependency for carbonyl modification of the neurofilament heavy subunit. The in vivo occurrence of this neurofilament modification in the neurofibrillary pathology of AD suggests that carbonyl modification is associated with a generalized cytoskeletal abnormality that may be critical in the pathogenesis of neurofibrillary pathology. Furthermore, the data presented here support the idea that extensive posttranslational modifications, including oxidative stress-type mechanisms, through the formation of cross-links, might account for the biochemical properties of NFTs and their resistance to degradation in vivo.

Alzheimer Disease↗
PubMed1995

Validation of a screening survey to assess local public health performance.

The study seeks to validate an abbreviated protocol for measuring local public health performance. Primary data were collected during 1993 on a series of indicators keyed to defined public health core functions and their associated practices. The data were obtained from responses provided by local health department directors and were reviewed for accuracy by respective state health department personnel. All local public health jurisdictions (370) in six states were surveyed with a screening protocol. A sample of 36 of these jurisdictions was then resurveyed by means of a full-length protocol using 84 different indicators of public health performance. Correlations between scores obtained from the screening survey and those from the reference survey were high for overall public health performance, for each of the three functions, and for some of the ten practices. A group of only four queries was shown to predict reliably the overall scores. Findings support the conclusion that public health practice can be defined, measured, and monitored. A proposed surveillance system is feasible.

Analysis of Variance↗
PubMed1995

Hemolytic differences among artificial cardiac valves used in a ventricular assist pump.

Ventricular assist devices (VADs) required for cardiac support may produce clinically significant hemolysis. VAD valves differ in both mechanics and hemodynamics. Therefore, we examined a ball valve, a modified tilting disc (MTD) valve, a polyurethane trileaflet valve, and a Björk-Shiley monostrut valve to determine their degrees of hemolysis. The valves were tested in a Pierce-Donachy VAD which pumped fresh bovine blood through a mock loop. Blood samples were analyzed for hematocrit and plasma hemoglobin, from which the indices of hemolysis were calculated. A one-way analysis of variance indicated significant differences between certain valves. The MTD was the most hemolytic. No significant hemolytic difference was found between the trileaflet and monostrut valves despite their different designs. The monostrut valve and the MTD valve were hemolytically very different despite their similar design. This study suggests that the valve type significantly affects the hemolysis produced by the VAD.

Animals↗
PubMed1995

Epidermal growth factor stimulates the restitution of rat gastric mucosa in vitro.

Epidermal growth factor (EGF) is mitogenic to gastric mucosal cells, protects against gastric mucosal injury induced by ulcerogenic agents, and stimulates cell migration in many systems. Restitution, the rapid re-establishment of mucosal integrity following damage, involves epithelial cell migration and can be monitored by measuring the transmucosal potential difference (PD) of tissue mounted in an Ussing chamber. The role of EGF in restitution is poorly characterized. To assess the effect of exogenous EGF on restitution, samples of rat gastric mucosa were mounted in an Ussing chamber with a solution of 10 nM EGF bathing either the mucosal or serosal surface. Matched control tissues from the same animals were untreated. Mucosal damage was induced by exposure of tissues to hyperosmolar sodium chloride. Restitution following injury was monitored by measuring the recovery of transmucosal PD, which reflects the degree of mucosal integrity. Undamaged mucosa maintained a PD of approximately -30 mV for several hours (mucosa negative with respect to serosa). Mucosal exposure to 1.2 M NaCl for 2 min reduced the PD to near 0 mV. Thereafter, the PD returned in approximately 60 min to plateau at a value representing maximal recovery. Tissues mucosally treated with 10 nM EGF recovered following damage to a maximum of 60.2 +/- 5.1% of pre-exposure PD, while matched controls recovered to only 46.2 +/- 5.8%, a significant difference. Tissues serosally treated with EGF recovered to 61.0 +/- 3.2% and matched controls recovered to 51.1 +/- 2.9%, also a significant difference. These results suggest that both serosally and mucosally applied EGF stimulates the restitution of rat gastric mucosa in vitro.

Animals↗
PubMed1995

Boundaries of the pSC101 minimal replicon are conditional.

The DNA segment essential for plasmid replication commonly is referred to as the core or minimal replicon. We report here that host and plasmid genes and sites external to the core replicon of plasmid pSC101 determine the boundaries and competence of the replicon and also the efficiency of partitioning. Missense mutations in the plasmid-encoded RepA protein or mutation of the Escherichia coli topoisomerase I gene enable autonomous replication of a 310-bp pSC101 DNA fragment that contains only the actual replication origin plus binding sites for RepA and the host-encoded DnaA protein. However, in the absence of a repA or topA mutation, the DNA-bending protein integration host factor (IHF) and either of two cis-acting elements are required. One of these, the partitioning (par) locus, is known to promote negative DNA supercoiling; our data suggest that the effects of the other element, the inverted repeat (IR) sequences that overlap the repA promoter, are mediated through the IR's ability to bind RepA. The concentrations of RepA and DnaA, which interact with each other and with plasmid DNA in the origin region (T. T. Stenzel, T. MacAllister, and D. Bastia, Genes Dev. 5:1453-1463, 1991), also affect both replication and partitioning. Our results, which indicate that the sequence requirements for replication of pSC101 are conditional rather than absolute, compel reassessment of the definition of a core replicon. Additionally, they provide further evidence that the origin region RepA-DnaA-DNA complex initiating replication of pSC101 also mediates the partitioning of pSC101 plasmids at cell division.

Bacterial Proteins↗
PubMed1995

Evaluating local public health performance at a community level on a statewide basis.

As part of efforts to develop a surveillance system to evaluate local public health performance, six state health departments surveyed local health departments in their states. Overall, 370 respondents (94 percent) returned completed surveys. Based on responses to 26 indicators, the mean percent community performance of the three core functions of public health was 56 percent of the potential score. Scores were also calculated for perceived adequacy of performance and for each of 10 practices linked to the three core functions. Variations in performance were related to population size, state, and administrative relationship of local jurisdictions to the state. These results suggest local public health performance can be evaluated at a community level on a statewide basis using a relatively small number of indicators.

Community Health Services↗
PubMed1995

Non-granular proteolytic enzymes of rat interleukin-2-activated natural killer cells. III. Enhancement of A-NKP 1, 2, and 3 proteolytic activities (cleaving after Arg, Phe and Pro) in response to interleukin-2.

Rat IL-2-activated natural killer (A-NK) cells contain a number of cytosolic proteases (A-NKP 1-3), two of which (A-NKP 2 and A-NKP 3) have been implicated in cytolytic function. The 3.2.3 monoclonal antibody directed against the NKRP-1 signal transduction molecule, a selective marker of rat NK cells, was used to select a highly purified population of rat NK cells. When the 3.2.3-positive cells were cultured in the presence of IL-2, a time-dependent increase in the specific activity of A-NKP 1, A-NKP 2 and A-NKP 3 was observed which paralleled the observed increase in lytic activity against both NK-sensitive (YAC-1) and NK-resistant (P815) targets. A transient rise was observed in the specific activity of N alpha-benzyloxycarbonyl-L-lysine thiobenzyl esterase (BLT esterase, i.e. granzyme A). These results lend further support to the hypothesis that A-NKP 2, a component of the rat A-NK cell multicatalytic proteinase complex/proteasome, and A-NKP 3 contribute to the cytolytic function of A-NK cells. Moreover, these results further suggest that proteolytic enzymes that contribute to cell-mediated cytotoxicity are not restricted to the granzymes or localized only in the lytic granules of effector cells.

Animals↗
PubMed1994

Autosomal dominant Lewy body parkinsonism in a four-generation family.

We report a family with autosomal dominant parkinsonism. The propositus developed parkinsonism at a relatively young age (45 years) and came to autopsy after a 6-year illness. She had typical features of Parkinson's disease except for an absence of rest tremor, although this was present in other family members. A diagnosis of Lewy body parkinsonism was confirmed by neuropathological examination. Additional pathological features included the presence of cortical Lewy bodies and anti-ubiquitin-positive neurites in the cornu Ammonis 2 and 3 (CA2-3) region of the hippocampus. This kindred is similar both clinically and pathologically to a few previously reported pedigrees, further strengthening recent evidence of a genetic etiology of some forms of Parkinson's disease.

Adult↗
PubMed1994

What's a woman doing in a place like this?

Medicine is not a science. It is an art that uses science to explore what William Harvey called "nature's closest secrets," that we may better minister to her children. We still need to remove some crackpot theories that have crept in, such as "holism." Even neurosurgery has a few. But we are beginning to humanize the traditional detached indifference and become the doctors we were meant to be. Our patients will be better for it. Society will be better for it. We will be better for it [1320]. In discussing the women's liberation movement in America, Reverend William Sloan Coffin once stated, "The woman who most needs liberating is the woman who lives inside of each man." This, I think, is the great awakening that the increasing influence of female physicians has brought about. Early twentieth century physicians, armed with a new science, became efficient fighters of disease. Disease was the enemy, the cure was the victory, and the patient was too often merely the environment in which the encounter was fought. This is what was taught in medical school and residency. It was necessary to learn the lesson well in order to be protected against the pain of others and to abort any insidious tendency to identify with their misery. Many teachers believed in preventing the enervating perils of "emotional involvement." This is not to say that physicians were unkind to their patients, merely that they kept their distance. Patients were treated with respect and even with a kind of formalized dignity. Physicians were as gentle as they knew how to be. But they were men apart. They towered over the sick as an adult towers over a child. Today something within men is being liberated. To a great extent, I believe that women physicians have been essential in bringing this change to medicine. We now know that physicians are not compromised by allowing themselves to feel some of what their patients feel. They are strengthened by it. A patient's life, the setting of his illness, the rending of his soul, the anguish of his family and the hope for his recovery have all become as much a part of good care as knowledge of the serum sodium and what to do about it. Men have become better nurturers, more empathetic. And the thing that is being liberated from inside men is something that society has always seen as a feminine quality. The peak of the healer's art is in bringing both science and empathy to bear on disease. This is what being a physician should mean.(ABSTRACT TRUNCATED AT 400 WORDS)

Europe↗
PubMed1994

The use of long-duration current pulses to assess nerve survival.

This study investigated the usefulness of long-duration current pulses in assessing the status of the auditory nerve in ears with various degrees of retrograde neural degeneration. Guinea pigs were deafened with aminoglycosides prior to acute implantation of the cochlea and collection of electrically evoked auditory brainstem responses (EABRs). Analysis of wave I evoked with long-duration current pulses suggests that this evoked response is sensitive to degeneration of the peripheral processes of the auditory nerve. Correlations with spiral ganglion cell density show that EABR measures obtained with long-duration pulses are comparable to those previously established for estimating nerve survival. Further analysis indicates that this measure may provide unique information about the degenerative state of the nerve. Threshold EABR measures using long-duration pulses are evidently more place-specific than other measures. Also, results suggest that long-duration pulses may be sensitive to two phases of the degenerative process: degradation of the peripheral processes and subsequent degeneration of neural processes central to the spiral ganglion.

Aminoglycosides↗
PubMed1994

Somataglycan-S: a neuronal surface proteoglycan defines the spinocerebellar system.

The formation and maintenance of functionally specific neuronal networks may depend on specific proteoglycans localized to the surface membranes of a subset of neurons. Monoclonal antibody (MAb) 6A2 labeled a distinct subset of CNS neurons: the somas and proximal dendrites of cells making up the spinocerebellar and reticular systems. These pathways contribute to proprioceptive and exteroceptive functions. Ultrastructurally, MAb 6A2 immunoreactivity was distributed focally along the cell surface membranes and the adjacent extracellular space. On western blots of immunoaffinity-purified preparations from cerebellar homogenates, a major, broad band of approximately 400 kDa is labeled by MAb 6A2. Increased electrophoretic mobility of the purified antigen after digestion with chondroitinase ABC and keratanase suggests that the antigen is a proteoglycan bearing chondroitin sulfate and keratan sulfate glycosaminoglycans. Unsulfated N-acetyl-galactosamine residues linked to unsaturated uronic acid constituted the initial disaccharide in the chondroitin sulfate glycosaminoglycan chains. N- and O-linked oligosaccharides on the core protein were detected by the biotinylated lectins wheat germ agglutinin and Jacalin, respectively, and by MAb anti-HNK-1. Lyase and glycosidase digests result in a 280-kDa band. This proteoglycan, somataglycan-S, may provide a key to the role of glycoconjugates in determining neuronal diversity and system specificity.

Animals↗
PubMed1994

A proposed method for assessing the performance of local public health functions and practices.

OBJECTIVES: One of the objectives for the nation for the year 2000 requires that 90% of the population be served by a local health department effectively carrying out the core functions of public health. This study proposes a method whereby determinations can be made of the extent to which a local public health jurisdiction is served by core public health functions, as well as the extent to which the functions are rendered by the health department. METHODS: Fourteen health departments under longitudinal study between 1979 and 1992 were studied. Respondents in each department completed a survey protocol using 81 indicators linked to standard public health functions and practices. Results are presented in graphic form, which provides a visual profile of public health performance for a local jurisdiction. RESULTS: The graphic profiles successfully differentiate one jurisdiction from another, and within each jurisdiction they differentiate the performance levels of different public health practices. The method enables identification of the full range of public health providers. CONCLUSIONS: Current definitions of public health practice have utility for evaluating public health performance. The validity of the proposed method deserves further study.

Data Collection↗
PubMed1993

Trends in HIV prevalence among disadvantaged youth. Survey results from a national job training program, 1988 through 1992.

OBJECTIVE: To describe trends in the prevalence of human immunodeficiency virus (HIV) among socially and educationally disadvantaged US youth. DESIGN: Analysis of demographic and geographic trends of HIV infection among Job Corps students from January 1988 through December 1992. SETTING: The Job Corps is a national training program for disadvantaged and out-of-school youth. POPULATION SCREENED: Youths aged 16 to 21 years who entered the Job Corps residential training centers during the survey period. MAIN OUTCOME MEASURE: Trends in prevalence of HIV infection among Job Corps students stratified by sex, age, race, and region of the country. RESULTS: Of the 269,956 Job Corps students screened, 812 (0.3%) tested positive for the antibody to HIV type 1. Seroprevalence of HIV for young men decreased from 3.6 per 1000 in 1988 to 2.2 per 1000 in 1992 (chi 2 test for trend, P < .001). Seroprevalence for young women increased from 2.1 per 1000 in 1988 to 4.2 per 1000 in 1990 (P = .001), with seroprevalence remaining stable from 1990 through 1992. The decreasing trends in HIV prevalence among men and increasing trends among women were primarily due to changes in seroprevalence in African-American students. CONCLUSIONS: The overall prevalence of HIV infection of three per 1000 is high, given the youth of Job Corps students. The significant rise in HIV rates among female Job Corps students provides evidence of the increasing risk of infection for socioeconomically disadvantaged young women. Reasons for the declining trend in HIV prevalence among male Job Corps students are not clear. Efforts to prevent the spread of HIV infection among adolescents must focus on the group that is hardest to reach--out-of-school and impoverished youth.

Adolescent↗