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D H Smith

Publications and source records attributed to D H Smith.

At least 127 records · Page 7Linked to original sources
PubMed1995

New magnetic resonance imaging techniques for the evaluation of traumatic brain injury.

Although current computerized tomography (CT) and magnetic resonance imaging (MRI) techniques have shown great utility in diagnosing various aspects traumatic brain injury, damage resulting from mild diffuse brain injury often goes undetected with these procedures. Newly developed MRI techniques, including magnetization transfer imaging (MTI) and diffusion-weighted imaging (DWI), have been proposed to have enhanced sensitivities for identifying damage induced by both diffuse and focal brain injury. Results from recent initial studies with experimental models of brain injury suggest that MTI may be useful for evaluating diffuse white matter damage, while DWI may demonstrate regions of focal contusion more acutely and with greater accuracy than conventional MRI procedures.

Brain Injuries↗
PubMed1995

Biomechanical analysis of experimental diffuse axonal injury.

The purpose of this paper is to present results from methodologies used in our laboratory that are targeted toward identifying specific brain injury thresholds. Results from studying one form of brain injury, diffuse axonal injury, are presented in this report. Physical models, or surrogates, of the skull-brain complex are used to estimate the relationship between inertial loading and brain deformation. A porcine model of diffuse axonal injury, developed with information from these physical models and earlier in vitro tissue modeling studies, is used to correlate histologic and radiologic evidence of axonal injury to predicted regions of injury from the experimental and theoretical analysis. These results form the basis for developing improved diffuse brain injury tolerance levels, as well as identifying new means of diagnostic and treatment techniques for diffuse axonal injury.

Animals↗
PubMed1995

The reliability of quantitative electroencephalography as an indicator of cerebral ischemia.

The electroencephalogram (EEG) has been used to detect episodes of cerebral ischemia during various surgical procedures. Recently, computerized systems for recording and interpreting the quantitative EEG (QEEG) have been used by anesthesiologists because of their ease of application, clarity of display, and reported ability to identify ischemic EEG changes. However, the extent to which automated techniques of QEEG interpretation reliably differentiate cerebral ischemia from the confounding effects of anesthetics and other sources of "artifact" is not completely established. In this study, EEGs were recorded before and after defibrillator testing in patients undergoing implantable cardioverter defibrillator (ICD) placement and during analogous time periods in control patients undergoing abdominal surgery. EEGs were subjected to standard visual inspection by an experienced electroencephalographer and QEEG analysis with a commercially available system was used for automated EEG interpretation in order to evaluate the reliability of this quantitative technique. The CIMON technique identified episodes which met previously defined criteria for QEEG cerebral dysfunction and ischemic pattern in both groups, despite the presumed absence of cerebral ischemia in the control patients. Since there was no evidence of cerebral ischemia in the raw EEGs of either the ICD patients or the controls, these QEEG changes were not confirmed by conventional techniques of EEG interpretation. Our results suggest that caution is warranted when using automated systems for intraoperative interpretation of EEG.

Adult↗
PubMed1995

The image of plastic surgeons in news media coverage of the silicone breast implant controversy.

We analyzed the portrayal of plastic surgeons in the media by using the qualitative method of narrative analysis of newspaper articles available between July 1991 and June 1992 and popular magazine articles available from 1965 through 1992 in the Tampa Bay area. Plastic surgeons were presented as antagonists in the "horror stories" of sick women, as combatants in a medical community divided in its assessment of health risks, and as profit-oriented businesspersons. Patients were fully developed heroines, whereas plastic surgeons were described negatively by their antagonists, which undermines the expertise, good character, and good will that determine credibility for plastic surgeons. Providing the press with stories about their own efforts to help patients might have helped plastic surgeons receive more favorable press and enhance their credibility. More sophisticated handling of underlying values and the problem of communicating safety also might have been helpful.

Breast Implants↗
PubMed1995

Cellular responses to experimental brain injury.

Little is known regarding the molecular (genomic) events associated with the pathophysiology of traumatic brain injury (TBI). This review focusses on the experimental efforts to date elucidating the acute alterations in expression of immediate early genes (IEGs), heat shock proteins (HSPs) and cytokines following experimental brain injury. The immediate early genes, c-fos, c-jun and junB were observed to be bilaterally induced in the cortex and hippocampus as early as 5 min following lateral fluid-percussion (FP) brain injury in the rat. While levels of c-fos and junB mRNA returned to control levels by 2h, c-jun mRNA remained elevated up to 6h post-injury. Increased levels of mRNA for the inducible heat-shock protein (hsp72) were observed up to 12h following injury and were restricted to the cortex ipsilateral to the impact site. Mild induction of the glucose-regulated proteins (grp78 and grp94), which share sequence homology with hsp72, was apparent in the ipsilateral cortex. The cytokines IL-1 beta and TNF alpha were induced at 1h following FP brain injury and remained elevated up to 6h post-injury. These data, while indicative of the complex genomic response to TBI, are also suggestive of the trauma-induced activation of multiple signal transduction pathways.

Animals↗
PubMed1995

Bioelectrical impedance analysis as an assessment of diuresis in congestive heart failure.

OBJECTIVE: To compare changes in bioimpedance parameters and calculated total body water (TBW) with conventional measurements used to assess the efficacy of diuretic therapy in the treatment of heart failure. SETTING: A Veterans Affairs tertiary care, teaching hospital. SUBJECTS: Twelve patients with New York Heart Association (NYHA) class III congestive heart failure (CHF). DESIGN: Prospective, consecutive sample, cohort, open label. INTERVENTIONS: Parenterally administered furosemide; clinically dictated, outcome-oriented, adjunctive therapy of CHF. OUTCOMES: Bioelectrical impedance analysis (BIA) parameters, measured volume of diuresis and changes in body weight, defined clinical endpoints (NYHA criteria). RESULTS: Three days of diuretic therapy with furosemide (oral and/or intravenous) for CHF was associated with a measured weight loss of 4.1 +/- 0.6 kg and statistically significant increases in resistance and reactance of 20.8% +/- 2.7% and 22.7% +/- 6.1%, respectively (p < 0.005). Calculated TBW using BIA parameters and standard equations decreased on average by 6.1 +/- 0.6 L or 11.2% +/- 1.1% (p < 0.001). A significant inverse correlation was observed between change in measured body weight and total body reactance (p = 0.02). CONCLUSIONS: Single-frequency BIA appears to have limited clinical usefulness as a method of assessing diuretic therapy in the management of CHF. Its greatest usefulness appears to lie in the assessment of serial changes in individual patients and patient populations that are physiologically or metabolically homogeneous. Further studies are needed to establish the validity of BIA in patients with decompensated CHF.

Administration, Oral↗
PubMed1995

Relationship of left ventricular structure to maximal heart rate during exercise.

Previous investigators using clinical, hemodynamic, or exercise parameters to predict maximal exercise heart rate (HRmax) have demonstrated age to be the major determinant. Regression coefficients have ranged from -0.3 to -0.6, leaving approximately two thirds of the variance in HRmax unexplained. Because cardiac size and function are directly related to stroke volume and should influence HRmax, we studied 114 male subjects (aged 19 to 73 years) with two-dimensional and M-mode echocardiography who underwent maximal treadmill testing with respiratory gas analysis. Seventy-three were normotensive (diastolic BP < 95 mm Hg) and 41 were hypertensive. As in previous studies, HRmax was inversely related to age (HRmax = 199-0.63[age], r = -0.47, p < 0.001). M-mode left ventricular (LV) diastolic dimension (LVD) added significantly to the explanation of the variance in HRmax (r = -0.57, p < 0.001) (HRmax = 236 - 0.72 [age]-6.8 [LVD]). Thus, the larger the heart, the lower the HRmax. No other echocardiographic measurement or derived parameter added significantly to the explanation of the variance in HRmax. To evaluate the effects of hypertension on HRmax, we studied hypertensives and normotensives separately. Only age was significantly related to HRmax in the normotensives (r = -0.50, p < 0.001). In the hypertensive subjects, however, both age and relative wall thickness (RWT) (which describes LV wall thickness in relation to LV chamber size) were significantly related to HRmax. Age explained 45% of the observed variance in HRmax (r = 0.67, p < 0.001) and RWT added modestly (9%) but significantly to the relationship (HRmax = 173-0.96[age]+94 [RWT], p < 0.001), together explaining 54% of the variance observed in HRmax. Thus, HRmax is inversely related to LVD and patients with larger ventricles achieve lower HRmax. In hypertensives, the amount of LV muscle mass in relation to chamber size is an additional predictor of HRmax. However, despite controlling for age, sex, and cardiovascular disease, and the inclusion of echocardiographic indices of cardiac size and function, a large portion of the variance in HRmax could not be explained. The unexplained variance in HRmax is most likely due to intersubject variability in resting cardiac size, volume, function, and other as yet undefined factors.

Adult↗
PubMed1995

Pharmacologic therapy for traumatic brain injury: experimental approaches.

An important feature of traumatic brain injury is that much of the ultimate damage appears to occur in a delayed or secondary fashion. Although the exact timing of these secondary sequelae has yet to be elucidated, recent experimental evidence suggests that an extended window of opportunity exists during which various forms of therapy appear to be efficacious. Moreover, new therapies have been developed which can be targeted at distinct pathophysiologic aspects of brain trauma. This article summarizes recent efforts to define secondary mechanisms of brain trauma and review the development of therapeutic strategies for reversing these deleterious events.

Animals↗
PubMed1995

Hypertension in the elderly: 24 h ambulatory blood pressure results from a placebo-controlled trial.

Calcium channel blockers are increasingly used to treat hypertension in elderly patients. To assess the effects of low-dose, long-acting verapamil on blood pressure (BP) and quality of life (QOL) in elderly patients, verapamil 120-240 mg of placebo was given once daily for 8 weeks to 76 patients aged > or = 60 years. After a 4-week placebo wash-out period, patients with a sitting DBP of 95-110 mm Hg and a mean daytime (6 am to 6 pm) ambulatory DBP > or = 90 mm Hg were entered into the study. Twenty four-hour BP monitoring as well as QOL self-assessment and digit span testing of cognitive function were performed at the end of the placebo wash-out and double-blind treatment periods. Patients treated with verapamil showed a significant decrease in mean whole-day BP, while those treated with placebo showed a small increase in BP. Treatment differences between the two groups in SBP and DBP were each statistically significant (P < 0.01). Significant differences were also seen when the 24 h period was divided into daytime and night-time readings. Both QOL and digit span testing scores were unchanged from baseline for verapamil-treated patients and were not different from the placebo-treated group. The results of this study demonstrate consistent and significant decreases in BP throughout the 24 h period with no adverse effects on QOL or cognitive function this this formulation of verapamil in elderly hypertensive patients.

Aged↗
PubMed1995

Metabolic and cardiovascular characteristics of hypertension. Familial aspects.

There are many convincing data showing that hypertension is an inherited syndrome of cardiovascular risk factors that clinically manifest at different times and occur independently of one another. These risk factors independently increase the potential for a patient to develop coronary heart disease, but when occurring together they appear to be synergistic in their ability to cause heart disease. It appears that in many patients high blood pressure may be a late manifestation of the disease process and may be indicative of a fairly advanced stage of disease. Moreover, it is possible that patients with the hypertension syndrome will develop coronary artery disease prior to the development of high blood pressure. We have recently demonstrated that when comparing cardiovascular risk factors in normotensive patients with a family history of hypertension to hypertensive patients with and without a family history of hypertension, there were no differences among the groups (Fig. 5). All three groups, however, were significantly worse off than normotensive subjects without a family history of hypertension. Thus, in terms of cardiovascular risk, these "normotensive hypertensive" patients were at a risk of developing heart disease equal to that of the hypertensive patients, the only difference being that there were not as many of such patients. The existence of the hypertension syndrome has some important diagnostic and therapeutic consequences. Because of our dependence on high blood pressure to isolate patients with the hypertension syndrome, it is unlikely that these patients will be treated. With an increased awareness of the presence of the hypertension syndrome and better screening techniques, it is likely that in the future we will be diagnosing and treating normotensive hypertension. We have demonstrated that when comparing normotensive hypertensive patients with truly hypertensive patients there are no differences in cardiovascular risk factors. The only difference between the groups is that the normotensive hypertensive patients do not have the high numbers (which may not be particularly important). It is thus likely that normotensive hypertensive patients have a risk of developing heart disease similar to that of truly hypertensive patients. For this reason, it is possible that normotensive patients with the hypertension syndrome will benefit from either conservative or pharmacologic therapy that reverses underlying cardiovascular risk factors without lowering the blood pressure. In treating high blood pressure in patients with the hypertension syndrome, it becomes important to select drugs that will reduce blood pressure while having a beneficial or at least a neutral effect on all of the other risk factors. Although the reduction in strokes and overall mortality in treated hypertensive patients warrants our continued enthusiasm for treating high blood pressure, an improved performance in reducing other cardiovascular risk factors adds to the benefits of antihypertensive therapy. Perhaps treating this disease as a syndrome rather than a number will result in a reduction in the incidence of coronary heart disease, as has been seen in the incidence of stroke.

Coronary Disease↗
PubMed1995

Controlling blood pressure throughout the day: issues in testing a new anti-hypertensive agent.

Lessons learned from ambulatory blood pressure (BP) monitoring strongly influence the development of new anti-hypertensive drugs. Efficacy should be demonstrated not only in the conventional clinical setting, but also throughout the full 24 h day, including the important early morning hours near the end of dosing intervals. Preservation of the circadian pattern, including appropriate day/night BP differences, may be a further important goal of therapy. The reproducibility of ambulatory monitoring measurements, together with the absence of placebo effects with this technique, adds greatly to its power and efficiency. Moreover, the use of ambulatory monitoring to accurately diagnose hypertension and exclude non-confirmed or white coat hypertensives from clinical trials adds further sensitivity to quantifying drug action. This technique was recently applied to the evaluation of the new angiotensin II receptor antagonist losartan. Hypertensive patients diagnosed by ambulatory monitoring were divided into four groups: placebo, losartan 50 mg once daily, 100 mg once daily or 50 mg twice daily. Compared with placebo, which had no effect, all three losartan regimens decreased SBP and DBP significantly. There was no difference in efficacy between the two once daily regimens, although 50 mg twice daily was slightly more effective than 50 mg once daily but not statistically significantly different from 100 mg once daily. However, all losartan groups exhibited sustained BP reductions throughout the 24 h dosing interval and preserved the circadian BP patterns. Ambulatory monitoring was thus able to accurately quantity the efficacy and the key chronobiological aspects of anti-hypertensive therapy with losartan in an efficient and cost-effective manner.

Adult↗
PubMed1994

Targeting of human immunodeficiency virus-infected cells by CD8+ T lymphocytes armed with universal T-cell receptors.

We have developed an immunotherapeutic approach with potential application in the treatment of viral and malignant disease. We show that primary CD8+ T cells isolated from peripheral blood can be genetically modified by retroviral transduction to express high levels of universal (major histocompatibility complex-unrestricted) chimeric T-cell receptors specific for human immunodeficiency virus (HIV) antigens. Two classes of HIV-specific URs in which the antigen-binding domain is comprised of either CD4 or a single-chain antibody are capable of activating a number of T-cell effector functions in response to target cells, including cytolysis, in a highly sensitive and specific manner. Importantly, we have addressed a number of issues which, although particularly relevant to the clinical application of this approach in the treatment of HIV infection, may also impact on the potential of UR immunotherapy for other disease targets. The UR immunotherapeutic system is particularly suited for evaluation in the clinical setting.

Animals↗
PubMed1994

Kynurenate is neuroprotective following experimental brain injury in the rat.

Pharmacologic inhibition of excitatory amino acid neurotransmission improves physiologic, metabolic, and neurobehavioral outcome following experimental brain trauma. However, no studies to date have demonstrated pharmacologically-induced attenuation of histopathological changes associated with experimental brain injury models. The present study examined the effects of kynurenate, an NMDA and non-NMDA receptor antagonist, on neuronal survival in the hippocampus after lateral fluid-percussion brain injury in the rat. Animals (n = 10/treatment) randomly received an intravenous injection of either kynurenate (300 mg/kg) or buffer (equal volume) 15 min following fluid-percussion brain injury of moderate severity. Two weeks after injury, animals were sacrificed and neuronal cell loss in the hippocampus was examined with Nissl staining. Selective loss of neurons in the CA3 region of the hippocampus, which has previously been characterized in this model of brain injury, was found to be significantly attenuated following kynurenate treatment (P < 0.05). These data suggest that pharmacologic compounds which are known to have beneficial effects on neurobehavioral and physiological outcome following brain injury may also significantly attenuate post-traumatic neuronal cell loss. Our results also support other recent data that pharmacological intervention with an excitatory amino acid receptor antagonist may be of therapeutic value in the treatment of brain injury.

Animals↗
PubMed1994

Persistent memory dysfunction is associated with bilateral hippocampal damage following experimental brain injury.

Memory dysfunction following head injury is a prominent feature in humans, yet the biological basis of this abnormality remains unknown. Following parasagittal fluid-percussion (FP) brain injury in the rat, we have previously observed profound spatial memory dysfunction relatively soon following injury (i.e. at 42 h). In the present study, we show that this memory dysfunction persists for at least 2 weeks following FP brain injury, and that it is associated with a selective bilateral loss of neurons in the dentate hilar region of the hippocampus. Given the important role of the hippocampus in memory, these observations may provide a potential anatomic substrate to explain, in part, the development posttraumatic memory deficits.

Animals↗
PubMed1994

Pulmonary hypoplasia associated with reduced thoracic space in mice with disproportionate micromelia (DMM).

BACKGROUND: Fetal mice homozygous for the Disproportionate micromelia (Dmm) gene were studied as a model for pulmonary hypoplasia in chondrodystrophy. METHODS: Wet weight, dry weight, and biochemical content were determined in excised whole lungs, terminal sac morphology and presence of multilamellar bodies were determined by electron microscopy, and volume of the thoracic space was estimated from paraffin casts. Lung development of the mutant was further assessed in whole organ culture. RESULTS. Compared with normal littermates, the mutant showed a significant decrease (28%) in lung wet weight without showing altered lung dry weight or tissue content of DNA and protein. The terminal sacs of lungs fixed by intratracheal instillation were significantly smaller than normal. However, the lungs appeared to have undergone maturation on schedule since the surfactant precursors, multilamellar bodies, were observed and normal tissue-levels of phospholipid were detected. The volume of the mutant's thorax was markedly reduced. Finally, the mutant's lungs when removed from the fetus prior to the onset of thoracic dystrophy (day 15) and cultured for three days demonstrated that, without the confining influence of a reduced thoracic space, they are capable of development comparable to normal. CONCLUSIONS: These findings support the hypothesis that the Dmm mutant can be further studied as a model for human pulmonary hypoplasia associated with chondrodystrophy, and that the relationship between the reduced thorax and the lung disorder is cause-and-effect.

Animals↗
PubMed1994

Distribution of forebrain diffuse axonal injury following inertial closed head injury in miniature swine.

Diffuse axonal injury (DAI) is one of the most frequently encountered types of brain damage resulting from closed head injury. This study was designed to verify whether DAI could be produced in miniature swine by rapid acceleration and deceleration of the head in the coronal plane. Hanford miniature swine (16-19 kg) were anesthetized with 3% isoflurane and their heads accelerated rapidly once through a 60-105 degrees arc in the coronal plane, producing only transient post-traumatic unconsciousness without prolonged coma. All animals made a good recovery and were sacrificed between 6 h and 10 days after injury. The response of forebrain projection systems to this injury was studied using neurofilament immunohistochemistry with antisera to nonphosphorylated (SMI-32) and phosphorylated (SMI-31) epitopes common to heavy (200 kDa) and medium (160 kDa) neurofilament proteins. In 9 of 12 animals, lesions characterized by foci of SMI-32 positive axonal retraction balls were present at the white matter/gray matter junction at the crests of gyri in the dorsolateral regions of the frontal, parietal, and temporal cortices and along margins of the lateral ventricles. A high density of pyramidal neuron perikarya in layers III and V within cortical gyri associated with subcortical DAI were intensely positive for SMI-31 immunohistochemistry. These results validate the use of miniature swine in studies of axonal injury and demonstrate that axonal injury analogous to that seen in the mildest form of DAI (grade I) can be produced in these animals without producing prolonged coma.

Animals↗
PubMed1994

A multiple antigen detection dipstick colloidal dye immunoassay for the field diagnosis of trypanosome infections in cattle.

Monoclonal antibodies (McAbs) were developed against aspartate aminotransferase purified from Trypanosoma brucei rhodesiense bloodstream form (bf) soluble extracts using a combination of anion-exchange and hydrophobic interaction chromatography. McAb 1A1 was Trypanozoon and Nannomonas specific while 2F1 was Trypanozoon bloodstream form specific. A dipstick colloidal dye immunoassay (DIA) was employed as a field diagnostic test for African trypanosome infections and designed using affinity purified polyclonal antibodies (PcAbs) raised against T. b. rhodesiense bf and the two McAbs, 1A1 and 2F1. PcAbs were adsorbed onto Palanil Red dye particles and used as dye reagents. Dipsticks were dotted with the three different antibodies, which captured trypanosomal antigens in samples tested, while the dye reagent bound to the captured antigens; the presence of coloured dots on the dipstick identified trypanosome infections. A field trial of the DIA was carried out in southeastern Uganda. A total of 1686 cattle from seven areas were bled and tested by DIA and haematocrit centrifuge technique (HCT). A total of 798 cattle (47.3%) were found to be trypanosomal antigen positive by DIA while only 162 (9.6%) were revealed to harbour trypanosomes by HCT, of which 151 (93%) were also positive by DIA.

Animals↗