Biomedical subjects

T R Miller

Publications and source records attributed to T R Miller.

At least 109 records · Page 6Linked to original sources

PubMed1994

Incidence and cost of alcohol-involved crashes in the United States.

The incidence of alcohol-involved highway crashes (those in which a driver or nonoccupant had been drinking) was estimated from federal data bases. The estimates were adjusted for police underreporting of alcohol involvement. In 1990, 22% of motor vehicle crash victims--1.2 million--were injured in crashes involving alcohol. Over 22,000 of these victims were killed. The comprehensive cost of alcohol-involved crashes was $148 billion in 1990, including $46 billion in monetary costs and $102 billion in lost quality of life. This represents $1.09 per drink of alcohol consumed. Crashes where blood alcohol concentration (BAC) exceeded .10% accounted for 32% of comprehensive crash costs, and crashes with lower positive BAC accounted for another 8%. Excluding drunk drivers and drunk nonoccupants, alcohol-involved crashes caused 8,500 deaths and left 21,000 people permanently disabled and another 605,000 less seriously injured. Averaged across all drinks, other people collectively pay $0.63 in crash costs every time someone takes a drink. A combination of increased public awareness and strong legal sanctions has been effective in reducing the incidence of alcohol-involved driving. The proportion of injuries in crashes that police reported were alcohol-involved dropped by 37% between 1982-1984 and 1990.

Accidents, Traffic↗

PubMed1994

Massively parallel computers for 3D single-photon-emission computed tomography.

Since the introduction of the expectation-maximization (EM) algorithm for generating maximum-likelihood (ML) and maximum a posteriori (MAP) estimates in emission tomography, there have been many investigators applying the ML method. However, almost all of the previous work has been restricted to two-dimensional (2D) reconstructions. The major focus and contribution of this paper is to demonstrate a fully three-dimensional (3D) implementation of the MAP method for single-photon-emission computed tomography (SPECT). The 3D reconstruction exhibits an improvement in resolution when compared to the generation of the series of separate 2D slice reconstructions. As has been noted, the iterative EM algorithm for 2D reconstruction is highly computational; the 3D algorithm is far worse. To accommodate the computational complexity, we have extended our previous work in the 2D arena and demonstrate an implementation on the class of massively parallel processors of the 3D algorithm. Using a 16000 processor MasPar machine, the algorithm is demonstrated to execute at 1.24 s/EM iteration for the entire 64 x 64 x 64 cube of 64 planar measurements obtained from the Siemens Orbiter rotating camera operating in the high-resolution mode.

Algorithms↗

PubMed1994

Ocular fibropapillomas of green turtles (Chelonia mydas).

Histologic evaluation of four eyes from three stranded juvenile green turtles (Chelonia mydas) from Florida, USA revealed ocular fibropapillomas composed of an overlying hyperplastic epithelium, various amounts of a thickened, well vascularized, collagenous stroma, and a moderate-to-dense population of reactive fibroblasts. The histologic morphology of the ocular fibropapillomas varied depending on whether the eyelid, conjunctiva, limbus, or cornea was the primary site of tumor origin. Fibropapillomas arising from the limbus, conjunctiva, or eyelid tended to be polyploid or pedunculated with a high degree of arborization. They often filled the conjunctival fornices and extended externally to be ulcerated on the distal aspects. Corneal fibropapillomas were more sessile and multinodular with less arborization. Some corneal tumors consisted primarily of a broad fibrovascular stroma and mild epithelial hyperplasia, whereas others had a markedly hyperplastic epithelium supported by stalks of fibrovascular stromal tissue. In green turtles ocular fibropapillomas may be locally invasive and associated with severe blindness and systemic debilitation.

Animals↗

PubMed1994

Novel CCK analogues and bombesin: a detailed analysis between phosphoinositide breakdown and high-dose inhibition of pancreatic enzyme secretion in three rodent species.

Cholecystokinin octapeptide (26-33) (CCK-8) stimulates pancreatic amylase secretion in a biphasic manner. Amylase secretion is stimulated in a dose-dependent manner up to a maximal level, but reduced secretion is observed at supramaximal concentrations. The downward portion of the dose-response curve has been referred to as "high-dose" inhibition. Recent studies with CCK-8 and Boc-Tyr(SO3H)-Nle-Gyl-Trp-Nle-Asp-2-phenylethylester (JMV-180) using rat acini have suggested that activation of the low-affinity CCK receptor leads to enhanced phosphoinositide (PI) breakdown, which in turn is responsible for high-dose inhibition of enzyme release. However, the secretory effect of JMV-180 varied considerably between rat and mouse. To explore further the relationship between PI breakdown and high-dose inhibition, we compared the effects of JMV-180 as well as the novel cholecystokinin tetrapeptide (30-33) Trp-Met-Asp-Phe-NH2 analogs A-70874 and A-57282, using rat, mouse and guinea pig pancreatic acini. The maximal secretory activity of CCK-8 was lowest (approximately 10% of total cellular amylase) in mouse, as compared with guinea pig and rat (approximately 15-20% of total amylase). The efficacies of A-70874, A-57282 and JMV-180 for stimulation of PI breakdown, relative to CCK-8, were 100, 100 and 45%, respectively, in mouse; 95, 70 and 20%, respectively, in rat and 75, 40 and 0%, respectively, in guinea pig.(ABSTRACT TRUNCATED AT 250 WORDS)

Amylases↗

PubMed1994

Clinical utility of bone scan features of pleural effusion: sensitivity and specificity for malignancy based on pleural fluid cytopathology.

UNLABELLED: Asymmetric chest activity with malignant and benign pleural effusions has been described in bone scans. However, the clinical utility of this finding is not elucible from the literature. We developed specific scintigraphic criteria for malignant pleural effusion and retrospectively assessed their sensitivity and specificity in a group of patient scans. METHODS: Pleural fluid was submitted for cytopathology from 850 patients over a 5-yr period. Bone scans were done within 2 mo of the thoracentesis in 74 patients. As a consensus panel, we reread the scans and reviewed the cytology. RESULTS: The effusions were cytologically malignant in 25/74 patients (34%), indeterminate in 9/74 (12%) and benign in 40/74 (54%). Based on cytopathology, malignant pleural effusions were detected by bone scans with a sensitivity of 34%-50% and a specificity of 78%-89%; true sensitivity and specificity was somewhere in between averaging 42% (95% confidence interval 24%-60%) and 84% (95% confidence interval 73%-95%), respectively. CONCLUSIONS: The bone scan is frequently the first examination suggesting pleural metastasis, and when it is detected it should be pursued beyond pleural fluid cytology, if negative or indeterminate.

Adult↗

PubMed1994

Measurement of global and regional left ventricular function by cardiac PET.

UNLABELLED: To permit assessment by positron tomography of left ventricular mechanical function, methods were developed to measure ejection fraction and regional wall motion and produce realistic images of the beating heart from ECG-gated PET data. METHODS: Following red cell labeling with 15O-carbon monoxide, seven-slice PET data were collected in list mode and reformatted into 16 time frames. Volume-rendered cine images were created by the depth-weighted maximum-activity method. To determine the left ventricular ejection fraction, background was subtracted in voxels outside the heart and the cubic datasets were rotated to the angle with the best septal separation. Depth weighting was applied to stimulate a 99mTc study, and the beating images were rendered by summing counts along parallel projection rays. These techniques were validated in 16 patients by comparison with planar studies performed with 99mTc-red cells. RESULTS: Visual grading of regional wall motion yielded exact agreement between the PET and 99mTc methods in 62% of walls with agreement with one grade in 94%. Assessment of quantitative regional wall motion agreed closely with an independent threshold edge detection method. CONCLUSION: PET techniques have been developed to measure left-ventricular ejection fraction and regional wall motion and to produce realistic beating images of the cardiac blood pool. This information can be obtained at the same time as measurements of perfusion and metabolism and in the same spatial orientation, thereby permitting quantitative assessment by positron tomography of global and regional mechanical function in relation to flow and metabolism.

Adult↗

PubMed1993

Peripheral cholecystokinin type A receptors mediate oxytocin secretion in vivo.

Cholecystokinin-octapeptide (CCK8) administered intraperitoneally (i.p.) in rats induces a rapid elevation in serum oxytocin (OT). The receptor subtype mediating this action of CCK was investigated with selective CCK-A and CCK-B receptor agonists and antagonists. CCK8 and A-71623, a potent CCK-A selective agonist, were similar in efficacy and potency for stimulating OT secretion. Both compounds at 10 nmol/kg elicited approximately one-half the response of 100 nmol/kg, which elevated serum OT to approx. 20 to 30-fold above basal level. The potent CCK-B selective agonist, A-63387, at doses up to 100 nmol/kg did not increase serum OT. MK-329, a CCK-A receptor selective antagonist, at a dose of 20 nmol/kg fully inhibited the action of 20 nmol/kg CCK8, while 100 nmol/kg of (R)L-365,260, a CCK-B selective antagonist, had no effect on the CCK8 response. These results, together with previous lesion studies, suggest that vagal CCK-A receptors in the periphery mediate the activation of the oxytocinergic pathway in vivo.

Animals↗

PubMed1993

Effect of exercise training on left ventricular performance in older women free of cardiopulmonary disease.

Endurance exercise training increases aerobic exercise capacity (maximal oxygen consumption rate [VO2max]) and attenuates the age-related decline in left ventricular (LV) function during exercise in older men. To determine whether similar adaptations occur in older women, 10 subjects (aged 63 +/- 4 years mean +/- SE) were studied before and after 9 to 12 months of endurance exercise training. They exercised 3.85 +/- 0.06 days/week at 81 +/- 0.3% of maximal heart rate. LV function at rest and during supine exercise was assessed by radionuclide ventriculography. VO2max was increased by 21% (from 1.40 +/- 0.1 to 1.7 +/- 0.1 liter/min; p < 0.001) in response to training. Maximal heart rate and systolic blood pressure during treadmill exercise were unchanged (161 +/- 5 beats/min before vs 164 +/- 3 beats/min after; p = NS, and 208 +/- 7 mm Hg before vs 214 +/- 8 mm Hg after; p = NS, respectively) after training. LV ejection fraction at rest (70.4 +/- 2% before vs 70 +/- 1% after) and during peak exercise (78.6 +/- 2% before vs 79.3 +/- 2% after) did not change in response to training. Furthermore, the increases in ejection fraction from rest to exercise were similar before and after training (change: 8.8 +/- 1 vs 9.1 +/- 1%). Stroke volume and cardiac output at peak exercise also did not change in response to training.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1993

Costs and functional consequences of U.S. roadway crashes.

The comprehensive cost of U.S. motor vehicle crashes was almost $333 billion in 1988. Comprehensive costs add the value of lost quality of life to monetary costs. This paper estimates costs by injury severity for three severity classification systems. It also estimates the functional capacity loss and probability of permanent work-related disability resulting from nonfatal injury. Using only monetary costs in safety decision making inappropriately favors mobility over safety. Comprehensive costs are one appropriate choice. Another acceptable choice is to use years of functional capacity loss plus direct costs to perform cost-effectiveness analysis.

Accidents, Traffic↗

PubMed1993

Double bond isosteres of the peptide bond: synthesis and biological activity of cholecystokinin (CCK) C-terminal hexapeptide analogs.

New and existing methodologies were used to prepare a series of modified CCK analogs in which each amide bond was replaced by a trans-alkene unit. The data indicate that every amide linkage at C-terminal tetrapeptide (CCK-4) region is crucial for biological activity. While the amide bond beyond the Trp residue in the N-terminal direction can be replaced by a trans-alkene and still retain most of the binding potency and functional activity.

Amino Acid Sequence↗

PubMed1993

Medically related motor vehicle injury costs by body region and severity.

For motor vehicle crashes, we estimated the medically related costs of nonfatal injury by body region and severity. Our primary data sources were paid charges reported in the Detailed Claims Information data base of the National Council on Compensation Insurance and injury incidence and severity reported in the National Highway Traffic Safety Administration's National Accident Sampling System (NASS). Brain and lower extremity injuries account for the largest portion of medical costs. Spinal cord and severe brain injuries cost more per case. Our average costs per case are very close to those in a report to Congress but come from completely different data sources. Thus, national data bases are providing consistent medical cost estimates.

Abdominal Injuries↗

PubMed1993

Upper and middle lobe bronchoalveolar lavage to diagnose Pneumocystis carinii pneumonia.

Pneumocystis carinii pneumonia (PCP) remains the most common lethal opportunistic pulmonary infection in patients infected with the human immunodeficiency virus (HIV). Although the use of prophylactic inhaled pentamidine has effectively reduced the frequency of primary and recurrent episodes of PCP, the aerosolization of pentamidine may have altered the localization of active PCP, resulting in more upper lobe disease. The distribution of disease may have also affected the diagnostic accuracy of standard bronchoalveolar lavage of the middle lobe, with a reduction in sensitivity from about 90 to 65%. In retrospective surveys of patients from our institution, Steiger and Fahy found that pooled multiple-lobe radiographic site-directed bronchoalveolar lavage resulted in diagnostic sensitivities of 91 and 100%, respectively. We performed a follow-up prospective study of 38 consecutive patients on aerosolized pentamidine in whom we lavaged both the middle lobe and an upper lobe. We found that bilobar lavage including routine lavage of an upper lobe increases the diagnostic sensitivity of bronchoalveolar lavage alone to 95% compared with 65% if lavage is performed only in the middle lobe (p < 0.05). Radiographic studies demonstrate a concordant increase in exclusive or predominant upper lobe disease in patients on aerosolized pentamidine, but our results indicate that PCP is recovered more frequently from the upper lobe regardless of the radiographic appearance. We conclude that all patients on prophylactic inhaled pentamidine should undergo bilobar lavage with the inclusion of an upper lobe in the initial evaluation of possible PCP. The diagnostic sensitivity of 95% makes bilobar bronchoalveolar lavage an acceptable sole initial diagnostic modality without the need for initial transbronchial lung biopsy.

AIDS-Related Opportunistic Infections↗

PubMed1993

Victim costs of violent crime and resulting injuries.

This DataWatch estimates the costs and monetary value of lost quality of life due to death and nonfatal physical and psychological injury resulting from violent crime. In 1987 physical injury to people age twelve and older resulting from rape, robbery, assault, murder, and arson caused about $10 billion in potential health-related costs, including some unmet mental health care needs. It led to $23 billion in lost productivity and almost $145 billion in reduced quality of life (in 1989 dollars). If associated deaths and cases resulting in psychological injury only are included, costs average $47,000 for rape, $19,000 for robbery, $15,000 for assault, and $25,000 for arson. Considering only survivors with physical injury, rape cost $60,000, robberies $25,000, assaults $22,000, and arson $50,000. Costs are almost $2.4 million per murder. Lifetime costs for all intentional injuries totaled $178 billion during 1987-1990.

Cost of Illness↗

PubMed1993

Cytomegalovirus pneumonitis. An unusual cause of pulmonary nodules in a patient with AIDS.

A patient with AIDS and a history of non-Hodgkin's lymphoma developed a generalized illness associated with the appearance of multiple pulmonary nodules on a chest radiograph. Cytomegalovirus infection was demonstrated by needle aspiration cytology. The patient's symptoms and radiographic abnormalities resolved completely on ganciclovir therapy. This unusual case (1) broadens the differential diagnosis of nodular pulmonary disease in patients with AIDS and (2) suggests that cytomegalovirus can cause clinically significant lung disease which may respond to standard antiviral therapy in patients with AIDS.

AIDS-Related Opportunistic Infections↗

PubMed1993

Rapidly converging iterative reconstruction algorithms in single-photon emission computed tomography.

Iterative reconstruction algorithms with markedly different convergence rates have been proposed in single-photon emission computed tomography (SPECT). Several new iterative reconstruction methods are described in this investigation. Differences between the methods include whether a ramp filter was used during backprojection, the type of backprojection weighting and whether camera and collimator blur were employed in the projection step. Simulated and real cylindrical phantoms with rod inserts were used to compare the properties of convergence and resolution following reconstruction by maximum likelihood (ML), iterative-Chang and the newly proposed reconstruction methods. Resolution was assessed after kernel-sieve regularization to achieve the same signal-to-noise ratio for all methods. Compared with maximum-likelihood reconstruction, methods employing a ramp converged much faster. One such method resulted in images with the same resolution and noise as ML, thus permitting termination of reconstruction at 14 iterations rather than the 1000 iterations required with ML. The major determinants of resolution were found to be use of an accurate model of the gamma camera imaging process in the projection step and inclusion of attenuation weighting and depth-dependent blur in the backprojection step. In summary, a new iterative reconstruction method was developed incorporating attenuation and blur and using a ramp filter that achieved results comparable to maximum-likelihood reconstruction in a fraction of the time.

Algorithms↗

PubMed1992

Synthesis and biological activity of CCK heptapeptide analogues. Effects of conformational constraints and standard modifications on receptor subtype selectivity, functional activity in vitro, and appetite suppression in vivo.

A series of modifications of the CCK7 analogue (des-NH2)Tyr(SO3-)-Nle-Gly-Trp-Nle-Asp-Phe-NH2 was prepared and tested for binding to guinea pig CCK-A and CCK-B receptors and in CCK-A-mediated functional assays. Selected analogues also were tested for appetite suppressant activity in rats. Several conformationally restricted residues in the C-terminal tetrapeptide region, including delta Z-Phe33, (N-Me)Phe33, (N-Me)Asp32, (N-Me)Leu31, and 3PP31 (3PP = trans-3-n-propyl-L- proline) were found to be acceptable modifications at one or both receptor subtypes. The (N-Me)Asp32 and (N-Me)Leu31 modifications afforded potent and selective CCK-A and CCK-B ligands, respectively. SAR studies in the N-terminal acyldipeptide region examined structural requirements for the side chain at position 28, where Gly and Pro replacements were found to possess high affinity at both receptor subtypes. Other conformationally restrictive modifications were less active. All of the analogues that showed high affinity (less than 10 nM) for the CCK-A receptor also were full agonists in amylase release and most were full or nearly full agonists in the phosphoinositide (PI) turnover assay, the most notable exception being the delta Z-Phe33 analogue, which showed 69% of the maximal response in the PI assay. Potent activity in suppression of food intake in rats was found for selected analogues.

Amino Acid Sequence↗

PubMed1992

Development of potent and selective CCK-A receptor agonists from Boc-CCK-4: tetrapeptides containing Lys(N epsilon)-amide residues.

A series of Boc-CCK-4 derivatives represented by the general structure Boc-Trp-Lys(N epsilon-COR)-Asp-Phe-NH2, where R is an aromatic, heterocyclic, or aliphatic group, are potent and selective CCK-A receptor agonists. These amide-bearing compounds complement the previously described urea-based tetrapeptides (Shiosaki et al. J. Med. Chem. 1991, 34, 2837-2842); structure-activity studies revealed parallel as well as divergent trends between these two series. A significant correlation was observed between pancreatic binding affinity and the resonance constant R of the phenyl substituent in one particular series of derivatives. Sulfation of phenolic amides appended onto the epsilon-amino group of the lysine did not affect affinity for the CCK-A receptor in contrast to the 500-fold increase in binding potency observed upon sulfation of CCK-8, suggesting that the lysine appendage and the sulfated tyrosine in CCK-8, both key structural elements that impart high affinity for the CCK-A receptor, are interacting differently with the receptor. The amide-bearing tetrapeptides are full agonists relative to CCK-8 in stimulating pancreatic amylase release while being partial agonists in eliciting phosphoinositide (PI) hydrolysis. Both effects were blocked by selective CCK-A receptor antagonists.

Amino Acid Sequence↗

PubMed1992

Principles of therapeutics.

Topical administration of drugs is the treatment of choice for diseases of the anterior segment. Drug levels attained by this means are usually of short duration, however, necessitating frequent therapy or continuous perfusion if prolonged drug levels are required. A drug-delivery device (collagen shield or contact lens) or subconjunctival injections can be used to augment topical therapy if frequent treatment is not possible. Subconjunctival injections are recommended for drugs that have low solubility and, hence, low corneal penetration. Retrobulbar injections are seldom indicated, except for regional anesthesia. Systemic administration is useful for anti-inflammatory therapy but it may be difficult to establish therapeutic levels of antibiotic agents in the eye because of the blood-ocular barrier. In severe cases, intraocular injection may be required.

Administration, Topical↗