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Biomedical subjects

B Miller

Publications and source records attributed to B Miller.

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

delta opioid receptor expression is induced by concanavalin A in CD4+ T cells.

Expression of delta opioid receptor mRNA in CD4+ T cells purified from Con A-stimulated murine splenocytes was demonstrated by reverse transcription-PCR and sequencing of the PCR products. mu and kappa opioid receptor mRNAs were not detected. Similar results were obtained in a single isolation of CD8+ T cells from Con A-stimulated splenocytes. mRNA for the delta opioid receptor was not detected in CD4+ T cells purified from either freshly isolated splenocytes or splenocytes cultured without Con A, and incubation of purified CD4+ T cells with Con A did not induce delta opioid receptor mRNA. It appears that quiescent CD4+ T cells do not express classic opioid receptors, but the delta-type receptor can be induced upon activation.

Animals↗
PubMed1996

Future directions for resuscitation research. IV. Innovative advanced life support pharmacology.

The topics discussed in this session include a partial review of laboratory and clinical studies examining the effects of adrenergic agonists on restoration of spontaneous circulation after cardiac arrest, the effects of varying doses of epinephrine, and the effects of novel vasopressors, buffer agents (NaHCO3, THAM, 'Carbicarb') and anti-arrhythmics (lidocaine, bretylium, amiodarone) in refractory ventricular fibrillation. Novel therapeutic approaches include titrating electric countershocks against electrocardiographic power spectra and of preceding the first countershocks with single or multiple drug treatments. These approaches need to be investigated further in controlled animal and patient studies. Epidemiologic data from randomized clinical outcome studies can give clues, but cannot document pharmacologic mechanisms in the dynamically changing events during attempts to achieve restoration of spontaneous circulation from prolonged cardiac arrest. Also, rapid drug administration by the intraosseous route was compared with intratracheal and intravenous (i.v.) drug administration. Many studies on the above treatments have yielded conflicting results because of differences between healthy hearts of animals and sick hearts of patients, differences in arrest (no-flow) times and cardiopulmonary resuscitation (CPR) (low-flow) times, different pharmacokinetics, different dose/response requirements, and different timing of drug administration during low-flow CPR versus during spontaneous circulation. The need to stabilize normotension and prevent rearrest by titrated novel drug administration, once spontaneous circulation has been restored, requires research. Most of the above topics require some re-evaluation in clinically realistic animal models and in cardiac arrest patients, especially by titration of old and new drug treatments against variables that can be monitored continuously during resuscitation.

Adrenergic Agonists↗
PubMed1996

Minority use of community long-term care services: a comparative analysis.

A series of national surveys since 1982 have examined health needs of elders. Small proportions of minority elders in each sample have limited our understanding of service use by minorities. This research sought to determine (1) the extent to which minorities have restricted use of community long-term care services as a result of socioeconomic status, family structure, and health status, and (2) the replicability and validity of results across three national surveys: Supplement on Aging, National Long-Term Care, and National Medical Expenditure. Results indicate no bivariate or multivariate differences between African American, Hispanic, or White frail older persons in use of community long-term services. Living arrangements, Medicaid use, and overall health and functional status were primary predictors of service use. Taking methodological limitations into account, the results suggest similarity in processes influencing use of community long-term care services for African American and White older persons.

Black or African American↗
PubMed1996

Overarm throws with the nondominant arm: kinematics of accuracy.

1. Overarm throws made with the nondominant arm are usually less accurate than those made with the dominant arm. The objective was to determine the errors in the joint rotations associated with this inaccuracy, and thereby to gain insight into the neural mechanisms that contribute to skill in overarm throwing. 2. Overarm throws from both left and right arms were recorded on different occasions as six right-handed subjects sat with a fixed trunk and threw 150 tennis balls at about the same speed at a 6-cm square on a target grid 3 m away. Joint rotations at the shoulder, elbow, wrist, and finger, and arm translations, were computed from recordings of arm segment orientations made with the magnetic-field search-coil technique. 3. All subjects threw less accurately in this task with the left (nondominant) arm. For throws made with the left arm, the height of ball impact on the target grid was related to hand trajectory length and to hand orientation in space at ball release, but not to hand trajectory height. 4. Two hypotheses were proposed to explain the decreased ball accuracy in the high-low direction during throwing with the nondominant arm: that it was caused by increased variability in the velocity or timing of onset of rotations at proximal joints (which determine the path of the hand through space) or increased variability in the velocity or timing of onset of finger extension (which determine the moment of ball release). 5. A prediction of the first hypothesis was that proximal joint rotations should be more variable in throws with the left arm. This was the case for the majority of proximal joint rotations in the six subjects when variability was examined in joint space. However, some proximal joint rotations were more variable in the right arm. 6. The first hypothesis was directly tested by determining whether hand angular position in space (which represents the sum of all proximal joint rotations) was related to ball impact height on the target grid at a fixed translational position in the throw. No relation was found between these variables for throws with the left arm in four subjects, whereas a weak relation was found for two subjects. It was concluded that, considering all subjects, the first hypothesis could not explain the results. 7. In contrast, in agreement with the second hypothesis, a strong relation (P < 0.001) was found in all subjects between ball impact height on the target grid and time of ball release for throws with the left arm, and with time of onset of finger extension. 8. Across all six subjects the timing precision (windows) for 95% of the throws was (for ball release) right arm, 9.3 ms; left arm, 22.5 ms; (for onset of finger extension) right arm, 13.7 ms; left arm, 26.7 ms. 9. Timing of onset of finger extension was no less accurate than timing of onset of other joint rotations for both left and right arms. However, simulations of throws showed that, for the same error in timing, finger extension had twice as large an effect on ball direction as any other joint rotation. Timing errors at the fingers have a greater effect than errors at other joints because finger errors are scaled by the higher angular velocity of the hand in space rather than by the smaller angular velocities of the individual joints. 10. It is concluded that although rotations were in general more variable at both proximal and distal joints of the nondominant (left) arm, the major cause of its decreased throwing accuracy was increased variability at the distal joints, i.e., in the timing of onset of finger extension. This may be due to a lack of precision in the commands from the right hemisphere to the left fingers in right-handed throwers.

Arm↗
PubMed1996

Relationship of aggressive behavior to other neuropsychiatric symptoms in patients with Alzheimer's disease.

OBJECTIVE: This study explored the relationship between aggressive behavior and other neuropsychiatric symptoms in patients with Alzheimer's disease. METHOD: Consecutively assessed outpatients with probable or possible Alzheimer's disease (N = 75) were assessed with the Behavioral Pathology in Alzheimer's Disease Rating Scale and the Hamilton Depression Rating Scale. RESULTS: Twenty-five patients (33%) had verbal outbursts and 13 patients (17%) engaged in physical aggression in the month prior to assessment. Aggressive patients and nonaggressive patients did not differ regarding age, education, gender, level of depression, or severity of dementia. In the entire group, dysphoria was found in 33%, delusional ideation in 39%, and hallucinations in 16%. Aggressive behavior was more frequent among patients with hallucinations than among those without. Scores on hallucinations and activity disturbance predicted 12% of the variance in total aggressive behavior. When data from patients taking psychotropic medication were excluded from the analysis, hallucination and delusion scores predicted 22% of the variance in the aggression score. Physical aggression was associated with activity disturbance and hallucinations, and verbal aggression was associated with delusional ideation. No other clinical correlates of aggression were identified. CONCLUSIONS: Aggressive behavior is a frequent behavioral symptom in Alzheimer's disease. About one-fourth of the variance in aggression could be attributed to psychosis.

Aged↗
PubMed1996

Determination of choline dehydrogenase activity along the rat nephron.

A radioenzymatic microassay was developed to quantitate choline dehydrogenase activity in single microdissected nephron segments. This enzyme is the rate limiting step in the biosynthesis of betaine, which serves as an intracellular osmoregulatory organic solute in mammalian kidney. The enzyme localized in renal mitochondrial inner membrane forms betaine aldehyde, which in the assay is converted to betaine by oxidative treatment. A histochemical procedure based on the formazan detection of tetranitroblue tetrazolium chloride was applied in parallel. The results show that activities in proximal convoluted and straight tubules are more than 5 times higher (21 to 25 pmol h-1 mm tubule-1) compared to distal nephron segments with no significant differences along the proximal tubule. Along the osmotic gradient from the outer medullary towards the papillary structures enzyme activities increased in ascending limbs of Henle's loop and collecting tubules. Collecting ducts showed two times higher activities than ascending loop segments when corrected for tubular cell volumes. The quantitative data were confirmed by the histochemical procedure. The results allow for the conclusion that betaine synthesis is sufficient to build up renal betaine, but cannot explain the distribution pattern of betaine along the corticopapillary axis. Additional mechanisms like intrarenal and tubular transport have to be postulated.

Alcohol Oxidoreductases↗
PubMed1996

Total hip and knee replacement treatment programs: a report using consensus.

Physical therapists may use varied treatment protocols for the acute care of patients with to hip or knee replacements. The purpose of this study was to develop, via consensus, a standardized treatment program for patients receiving total hip or knee replacement for primary osteoarthritis. Eighteen clinicians nationwide participated in a three-round consensus process. In Round 1, over 80% of the panel identified exercise, transfers, ambulation, and discharge criteria as the important treatment categories. In Round 2, they reviewed the preliminary physical therapy treatment program and recommended additional exercise regimes. In Round 3, 76% of the panel accepted the final total hip replacement program while 70% of the panel accepted the total knee replacement program. Using the consensus development process, physical therapists may begin to define their treatment programs which is fundamental to establishing a baseline standard of care.

Hip Prosthesis↗
PubMed1996

Cerebral resuscitation from cardiac arrest: treatment potentials.

In 1961, in Pittsburgh, PA, "cerebral" was added to the cardiopulmonary resuscitation system (CPR --> CPCR). Cerebral recovery is dependent on arrest and cardiopulmonary resuscitation times, and numerous factors related to basic, advanced, and prolonged life support. Postischemic-anoxic encephalopathy (the cerebral postresuscitation disease or syndrome) is complex and multifactorial. The prevention or mitigation of this syndrome requires that there be development and trials of special, multifaceted, combination treatments. The selection of therapies to mitigate the postresuscitation syndrome should continue to be based on mechanistic rationale. Therapy based on a single mechanism, however, is unlikely to be maximally effective. For logistic reasons, the limit for neurologic recovery after 5 mins of arrest must be extended to achieve functionally and histologically normal human brains after 10 to 20 mins of circulatory arrest. This goal has been approached, but not quite reached. Treatment effects on process variables give clues, but long-term outcome evaluation is needed for documentation of efficacy and to improve clinical results. Goals have crystallized for clinically relevant cardiac arrest-intensive care outcome models in large animals. These studies are expensive, but essential, because positive treatment effects cannot always be confirmed in the rat forebrain ischemia model. Except for a still-elusive breakthrough effect, randomized clinical trials of CPCR are limited in their ability to statistically document the effectiveness of treatments found to be beneficial in controlled outcome models in large animals. Clinical studies of feasibility, side effects, and acceptability are essential. Hypertensive reperfusion overcomes multifocal no-reflow and improves outcome. Physical combination treatments, such as mild resuscitative (early postarrest) hypothermia (34 degrees C) plus cerebral blood flow promotion (e.g., with hypertension, hemodilution, and normocapnia), each having multiple beneficial effects, achieved complete functional and near-complete histologic recovery of the dog brain after 11 mins of normothermic, ventricular fibrillation cardiac arrest. Calcium entry blockers appear promising as a treatment for postischemic-anoxic encephalopathy. However, the majority of single or multiple drug treatments explored so far have failed to improve neurologic outcome. Assembling and evaluating combination treatments in further animal studies and determining clinical feasibility inside and outside hospitals are challenges for the near future. Treatments without permanent beneficial effects may at least extend the therapeutic window. All of these investigations will require coordinated efforts by multiple research groups, pursuing systematic, multilevel research--from cell cultures to rats, to large animals, and to clinical trials. There are still many gaps in our knowledge about optimizing extracerebral life support for cerebral outcome.

Animals↗
PubMed1995

A column-switching high-performance liquid chromatographic assay for a novel cytotoxic thioxanthone derivative (WIN 33377) in mouse plasma with toxicokinetic results from a mouse LD10 study.

WIN 33377 (I) is a member of a novel class of cytotoxic antitumor agents, 4-aminomethyl thioxanthone derivatives. A simple, rapid and reproducible method has been developed for the assay of I in mouse plasma using a high-performance liquid chromatographic method utilizing a column-switching technique. The method involves direct injection of buffered plasma to the extraction column for sample clean-up followed by switching onto an analytical column for analysis with UV detection at 256 nm. The method has demonstrated accuracy and precision over the range 10-2500 ng/ml using a 100-microliters plasma sample with a minimum quantifiable level at 10 ng/ml. Stability of mouse plasma samples was demonstrated after storage for 4 weeks at -15 to -20 degrees C, as was the ability of samples to be accurately quantified after a maximum of three freeze-thaw cycles. Recovery was greater than 87% for the compound and the internal standard. The assay was accurate and reproducible with measured values lying within the limits of defined acceptance criteria. The utility of the method was demonstrated by analyzing plasma samples obtained from mice dosed with I as part of a pre-clinical safety study intended to assist in the design of a pharmacokinetically guided dose escalation strategy.

Animals↗
PubMed1995

Chondroitin sulfate proteoglycans in the developing cerebral cortex: the distribution of neurocan distinguishes forming afferent and efferent axonal pathways.

The first thalamocortical axons to arrive in the developing cerebral cortex traverse a pathway that is separate from the adjacent intracortical pathway for early efferents, suggesting that different molecular signals guide their growth. We previously demonstrated that the intracortical pathway for thalamic axons is centered on the subplate (Bicknese et al. [1994] J. Neurosci. 14:3500-3510), which is rich in chondroitin sulfate proteoglycans (CSPGs; Sheppard et al. [1991] J. Neurosci. 11:3928-3942), whereas efferent axons cross the subplate to exit in a zone containing much less CSPG. To define the molecular composition of the subplate further, we used antibodies against CSPG core proteins and chondroitin sulfate disaccharides in an immunohistochemical analysis of their distribution in the developing neocortex of the rat. Immunolabeling for neurocan, a central nervous system-specific CSPG (Rauch et al. [1992] J. Biol. Chem. 267:19537-19547), and for chondroitin 6-sulfate and unsulfated chondroitin becomes prominent in the subplate before the arrival of thalamic afferents. Immunolabeling is initially sparse in the cortical plate but appears later in maturing cortical layers. A postnatal decline in immunolabeling occurs uniformly for most proteoglycans, but, in the somatosensory cortex, labeling for neurocan, phosphacan, and chondroitin 4- and 6-sulfate declines in the centers of the whisker barrels before the walls. In contrast to neurocan, immunolabeling for other proteoglycans is either uniformly distributed (syndecan-1, N-syndecan, 5F3, phosphacan, chondroitin 4-sulfate), restricted to axons (PGM1), distributed exclusively on nonneuronal elements (2D6, NG2, and CD44), or undetectable (9.2.27, aggrecan, decorin). Thus, neurocan is a candidate molecule for delineating the intracortical pathway of thalamocortical axons and distinguishing it from that of cortical efferents.

Afferent Pathways↗
PubMed1995

Reduction of beta-amyloid peptide42 in the cerebrospinal fluid of patients with Alzheimer's disease.

In this clinical study the cerebrospinal fluid (CSF) level of a novel form of the beta-amyloid peptide (A beta) extending to position 42 (A beta 42) was determined in patients with Alzheimer's disease (AD) as well as controls. In addition to measurement of CSF A beta 42 levels, total A beta peptides, microtubule-associated protein tau, and apolipoprotein E (ApoE) genotype were also assessed. It is interesting that CSF A beta 42 levels were found to be significantly lower in AD patients relative to controls, whereas total A beta levels were not. A beta 42 has recently been shown to preferentially deposit in the brain tissue of patients with AD, suggesting that diminished clearance may account for its reduction in CSF. As previously reported, tau levels were increased in AD patients; however, neither A beta 42 nor tau levels were apparently influenced by the ApoE genotype.

Aged↗
PubMed1995

Intestinal fistulae formation following pelvic exenteration: a review of the University of Texas M. D. Anderson Cancer Center experience, 1957-1990.

Intestinal fistulae are an uncommon but serious complication of pelvic exenteration. To characterize factors leading to fistula formation and to define optimal management of this complication, we reviewed 533 cases of patients who underwent pelvic exenteration at the University of Texas M. D. Anderson Cancer Center between 1957 and 1990. Forty-two of those patients developed an intestinal fistula following total (n = 29), anterior (n = 12), or posterior (n = 1) exenteration which was not tumor related. Prior to routine pelvic floor reconstruction, the fistula rate was 16%. With the advent of omental pedicle grafts and gracilis flaps, the rate decreased to 4.5%. The fistulae described included those from the small bowel to the pelvic cavity (n = 15) or the neovagina (n = 8), and from the large bowel to the neovagina (n = 8). Complex fistulae were noted in 11 patients. Early fistulae, those that developed during initial hospitalization, occurred in 25 patients and were mainly related to infectious complications. Twenty-three patients underwent attempted surgical repair of fistulae. Eleven died during their hospitalization of sepsis, recurrent wound complications, or fistula. Late fistulae, those that developed after discharge, occurred in 17 patients and were mainly related to delayed healing. Early and late fistulae did not differ in location. Only two patients with late fistula formation died from complications of therapy. Significant long-term morbidity, however, included short bowel syndrome. Based on our review, we conclude the following: (1) Pelvic floor reconstruction, careful attention to surgical technique and aggressive treatment of infections reduces the risk of early fistula formation; (2) in cases associated with significant infection, treatment should be surgical; and (3) in stable patients, conservative management with hyperalimentation and bowel should be considered.

Female↗