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Biomedical subjects

B C Allen

Publications and source records attributed to B C Allen.

At least 37 records · Page 2Linked to original sources

Detection of cerebral hypoperfusion during trial carotid occlusion with reversal following extracranial-intracranial bypass prior to permanent occlusion.

The authors describe a patient with a large intracavernous aneurysm of the right internal carotid artery and a marked decrease in focal brain blood flow induced by temporary carotid balloon occlusion. The patient subsequently underwent a superficial temporal to middle cerebral artery bypass followed by successful carotid occlusion using detachable balloons placed proximal to the aneurysm. Postoperative rCBF demonstrated normal perfusion in the region of the right internal carotid artery distribution as well as normalization of perfusion to a previous area of baseline perfusion abnormality. Cerebral brain blood flow imaging was useful in the initial evaluation as well as the management of this patient.

Aged↗

A clinical study of the parameters and effects of temporary arterial occlusion in the management of intracranial aneurysms.

Temporary occlusion of intracranial arteries has emerged as a valuable technical adjunct in the management of intracranial aneurysms. The current study considered 121 patients (from a group of 234 consecutive aneurysm patients treated during a 2-yr period) who underwent elective temporary arterial occlusion. Twenty-one patients were excluded from further study because of an intraoperative rupture of an aneurysm, the elective sacrifice of afferent or efferent vessels, or the performance of an extracranial-intracranial arterial bypass graft; the remaining 100 patients underwent elective temporary occlusion under a standard neuroanesthetic regimen, including etomidate-induced burst suppression, normotension, normovolemia, and normothermia. In the postoperative period, radiographic evidence of ischemic brain injury in the distribution of the arteries occluded was selected as the end point for the failure of occlusion tolerance. The parameters evaluated with respect to this end point included the duration and nature of the temporary arterial occlusion, the number of the occlusive episodes, the specific vascular territory occluded, patient age, neurological status, presence of subarachnoid hemorrhage, vasospasm, and aneurysm size. Several parameters were found to be related to the postoperative development of ischemic injury. Patients more than 61 years of age and those in poor neurological condition (Hunt and Hess Grades III to IV) did not tolerate temporary occlusion as well as patients who were younger and in better condition. Patients occluded for less than 14 minutes routinely tolerated the iatrogenic ischemia; the 95% confidence level for the toleration of occlusion without the development of infarction occurred at 19 minutes. All patients occluded for more than 31 minutes had both clinical and radiographic evidence of cerebral infarction.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Diagnostic applications of simultaneously acquired dual-isotope single-photon emission CT scans.

PURPOSE: To report the development and validation of a technique of dual tracer single-photon emission CT brain imaging using technetium-99m hexamethylpropyleneamine oxime and iodine-123 iodoamphetamine agents and the application of this technique in patients with a variety of diagnoses. METHODS: Contamination between the two isotopes' energy windows was calculated by opening both energy windows while scanning a group of patients using a single isotope. To compare uniformity of I-123 down-scatter, Tc-99m studies were performed both before and after the administration of I-123 in five of 24 dual studies. The 24 patients studied with the dual-isotope technique were evaluated during acetazolamide testing, trial balloon occlusion, or embolization of an arteriovenous malformation. RESULTS: In a dual acquisition, average count contamination of an I-123 study by Tc-99m was less than 1% of the total I-123 counts, and contamination of a Tc-99m study by I-123 was approximately 12% of the total Tc-99m counts. Tc-99m studies performed both before and after the administration of I-123 demonstrated that contaminating counts do not adversely affect scan interpretation. Dual-tracer scans were completed in all 24 patients, 10 of whom showed changes after intervention. CONCLUSIONS: Dual-tracer single-photon emission CT brain scans of adequate diagnostic quality are possible using Tc-99m and I-123.

Acetazolamide↗

Pharmacokinetic modeling of trichloroethylene and trichloroacetic acid in humans.

The development and application of appropriate physiologically based pharmacokinetic (PBPK) models of chemical contaminants will provide a rational basis for risk assessment extrapolation. Trichloroethylene (TCE) is a widespread contaminant found in soil, groundwater, and the atmosphere. Exposures to TCE and its metabolites have been found to be carcinogenic in rodents. In this study, a PBPK model for TCE and its major metabolite, trichloroacetic acid (TCA), is developed for humans. The model parameters, estimated from the relevant published literature on human exposures to TCE and its metabolites, are described. Key parameters describing the metabolism of TCE and the kinetics of TCA were estimated by optimization. The optimization was accomplished by simultaneously matching model predictions to observations of TCE concentrations in blood and exhaled breath, TCA plasma concentrations, and urinary TCA excretion from five published studies. The optimized human PBPK model provides an excellent description of TCE and TCA kinetics. The predictions were especially good for TCA plasma concentrations following repeated TCE inhalation, an exposure scenario similar to that occurring in the workplace. The human PBPK model can be used to estimate dose metrics resulting from TCE exposures and is therefore useful when considering the estimation of human health risks associated with such exposures.

Carcinogens↗

Evaluating the risk of liver cancer in humans exposed to trichloroethylene using physiological models.

Trichloroethylene (TCE) is a widespread environmental pollutant. TCE is classified as a rodent carcinogen by the U.S. Environmental Protection Agency (EPA). Using the rodent cancer bioassay findings and estimates of metabolized dose, the EPA has estimated lifetime exposure cancer risks for humans that ingest TCE in drinking water or inhale TCE. In this study, a physiologically based pharmacokinetic (PB-PK) model for mice was used to simulate selected gavage and inhalation bioassays with TCE. Plausible dose-metrics thought to be linked with the mechanism of action for TCE carcinogenesis were selected. These dose-metrics, adjusted to reflect an average amount per day for a lifetime, were metabolism of TCE (AMET, mg/kg/day) and systemic concentration of TCA (AUCTCA, mg/L/day). These dose-metrics were then used in a linearized multistage model to estimate AMET and AUCTCA values that correspond to liver cancer risks of 1 in 1 million in mice. A human PB-PK model for TCE was then used to predict TCE concentrations in drinking water and air that would provide AMET and AUCTCA values equal to the predicted mice AMET and AUCTCA values that correspond to liver cancer risks of 1 in 1 million. For the dose-metrics, AMET and AUCTCA, the TCE concentrations in air were 10.0 and 0.1 ppb TCE (continuous exposure), respectively, and in water, 7 and 4 micrograms TCE/L, respectively.

Animals↗

Brain blood flow SPECT in temporary balloon occlusion of carotid and intracerebral arteries.

It is important to determine preoperatively which patients can tolerate permanent occlusion of a cervical internal carotid or cerebral artery when such a procedure may be necessary to treat cerebrovascular or neoplastic lesions. Here we report our experience in combining temporary intra-arterial balloon occlusion with concomitant cerebral blood flow imaging in preoperative evaluation of such patients. Forty-two patients with a variety of cerebrovascular and neoplastic lesions underwent trial balloon occlusion of an internal carotid or intracerebral artery. Eight patients developed both neurologic symptoms as well as brain perfusion defects during trial occlusion. Nine others developed only perfusion defects. The remainder were asymptomatic and had negative scans. Brain blood flow imaging during intra-arterial balloon occlusion identified 17 patients potentially at risk for developing postsurgical ischemic deficits. Treatment alternatives to acute arterial sacrifice were developed for these patients.

Adolescent↗

Physiologically based pharmacokinetic modeling with trichloroethylene and its metabolite, trichloroacetic acid, in the rat and mouse.

The uptake and metabolism of trichloroethylene (TCE), and the stoichiometric yield and kinetic behavior of one of its major metabolites, trichloroacetic acid (TCA), were compared in Fischer 344 rats and B6C3F1 mice using a physiological model. Physiologically based pharmacokinetic (PB-PK) model parameters (metabolic rate constants and tissue partition coefficients) were determined in male and female B6C3F1 mice and were taken from the literature for the male and female Fischer 344 rats. The kinetic behavior of TCA was described by a classical one-compartment model linked to a PB-PK model for TCE. The TCE blood/air partition coefficients for male and female mice, determined by vial equilibration, were 13.4 and 14.3. The Vmaxe values for male and female mice, using gas uptake techniques, were 32.7 +/- .06 and 23.2 +/- 0.1 mg/kg/hr and the Km was 0.25 mg/liter. The PB-PK model for TCE adequately described the uptake and clearance of TCE in male and female rats exposed to a single, constant concentration of TCE vapor, but failed to describe the uptake and clearance of TCE in male and female mice exposed to a wide range TCE vapor concentrations. Computer-predicted blood concentrations of TCE were generally greater than observed blood concentrations of TCE. The stoichiometric yield of TCA in mice exposed to these TCE vapors was concentration dependent. The capacity for oxidation of TCE was much greater in B6C3F1 mice than in Fischer 344 rats, and as a result the systemic concentration of TCA was greater in these mice than rats. An increased body burden of TCA in B6C3F1 mice may be related to the formation of hepatocellular carcinomas in B6C3F1 mice exposed to TCE.

Administration, Inhalation↗

HMB-45 detection in adenocarcinomas.

Several studies have suggested that HMB-45 is a specific marker for melanoma, presumably due to its ability to detect a glycoprotein that is present in premelanosomes. The present study was conducted to evaluate whether HMB-45 is an absolutely specific antigenic determinant for melanoma and the role that testing with this antibody has in the differential diagnostic workup of amelanotic melanoma vs adenocarcinoma. Formaldehyde solution-fixed, paraffin-embedded tissue samples from 52 adenocarcinomas (primary or metastatic) and five melanomas (two primary and three metastatic) were immunostained with the use of a commercially available monoclonal antibody (MoAb), ie, HMB-45 (Enzo), a polyclonal antibody to S100 protein, a wide-spectrum keratin polyclonal antibody, and a keratin MoAb, ie, AE1/AE3. Approximately 10% (ie, 9.6%) of the adenocarcinomas (five cases) expressed HMB-45 with varied intensity and distribution. Positive primary tumors (n = 3) included one each from the breast, colon, and kidney; positive metastatic tumors (n = 2) included one each from the breast and endometrium. Fifty-two percent of the adenocarcinomas were positive for S100 protein. One renal carcinoma was negative for both keratins when tested with the AE1/AE3 MoAb and polyclonal antibody (Dako). This was the only adenocarcinoma that was negative when the keratin polyclonal antibody (Dako) was used. All but one additional adenocarcinoma demonstrated keratin expression when the AE1/AE3 MoAb was used for testing. This study showed that HMB-45 is not absolutely specific for melanoma. HMB-45 may react with some adenocarcinomas, at least when tested with the commercially available MoAb (Enzo). This fact, in conjunction with aberrant keratin expression by some melanomas and S100 protein expression by adenocarcinomas and other neoplasms other than melanomas, should be considered when antibody panels are evaluated in the workup of poorly differentiated tumors. However, HMB-45 appears to be the most specific marker that is available at the present time for supporting a diagnosis of melanoma.

Adenocarcinoma↗

Failure of surgery to improve outcome in hypertensive putaminal hemorrhage. A prospective randomized trial.

Hypertensive putaminal hemorrhage remains a major cause of hemorrhagic stroke carrying extremely high morbidity. Considerable controversy remains regarding the optimal form of therapy. Between 1983 and 1989 we conducted a prospective randomized trial with three treatment strategies: best medical management, best medical management plus intracranial pressure monitoring, and surgical evacuation. Only patients with significant deficit harboring a putaminal hematoma at least 3.0 cm in diameter were entered. The study was interrupted after 21 patients had been studied (9, best medical management; 4, intracranial pressure monitoring; and 8, surgical evacuation). No differences were found among groups for age, admission blood pressure, and time interval between onset of symptoms and arrival at hospital. None of the subjects were capable of returning to prestroke activity. Fifteen (71%) died or remained vegetative at 6 months, and only 4 (19%) were capable of independent life at home. Of the 9 patients in the best medical management arm, 7 were dead or vegetative. In the surgical group, 4 patients died and only 2 were capable of independent life. These results suggest that current medical and neurosurgical therapies remain ineffective in preventing the devastating neurologic consequences of hypertensive putaminal hemorrhage.

Adult↗

Post-traumatic cysts and cyst-like lesions of bone.

We describe two patients with cyst-like lesions of bone that developed at sites of healed or healing fractures. One case showed histological features of a unicameral bone cyst, which, to the best of our knowledge, is a previously unreported finding in a post-traumatic cyst. It is suggested that there are two principal clinical and radiological types of post-traumatic cyst, of which each of our cases represents an example: (1) asymptomatic transient cortical lesions, found only in children, and (2) more central expanding lesions, found in a wider age group and associated with pain, swelling, and pathological fractures.

Bone Cysts↗

Correlation between carcinogenic potency of chemicals in animals and humans.

Twenty-three chemicals were selected for comparison of the carcinogenic potencies estimated from epidemiological data to those estimated from animal carcinogenesis bioassays. The chemicals were all those for which reasonably strong evidence of carcinogenicity could be found in humans or animals and for which suitable data could be obtained for quantifying carcinogenic potencies in both humans and animals. Many alternative methods of analyzing the bioassay data were investigated. Almost all of the methods yielded potency estimates that were highly correlated with potencies estimated from epidemiological data; correlations were highly statistically significant (p less than 0.001), with the corresponding correlation coefficients ranging as high as 0.9. These findings provide support for the general use of animal data to evaluate carcinogenic potential in humans and also for the use of animal data to quantify human risk.

Animals↗

Hematologic effects of benzene: a thirty-five year longitudinal study of rubber workers.

We studied over 17,000 peripheral blood counts, accumulated during surveillance from 1940 through 1975, from a cohort of 459 benzene-exposed workers. Linear regressions demonstrated significant decreases in white and red cell counts, as well as hemoglobin, for workers exposed during the 1940's, without persistent trends over the ensuing 25 years. Strongly positive correlations were observed between these blood count fluctuations and fluctuations in retrospective estimates of benzene exposures for this plant for the earlier periods of surveillance (mean estimated exposure 1940 to 1948, 75 ppm), but not for later years (mean estimated exposure 1948 to 1975, 15 to 20 ppm). These data suggest substantial limitations of hematologic examination of populations to detect abnormalities in populations currently exposed to benzene. The data also demonstrate a novel approach to the biological validation of exposure estimates based upon limited industrial hygiene and historical record data.

Benzene↗

Time-related factors in quantitative risk assessment.

In regulatory or decision-making contexts related to carcinogenic hazards, one would like to know the extra risks associated with various levels, durations, and ages of exposure to a carcinogen. To supply that information, quantitative risk assessments are required that make extrapolations on variables related to dose levels, timing of exposure, and age. Quantitative models that express age-specific mortality rates as functions of the exposure pattern and that allow such extrapolations to be made are presented. The uncertainty inherently associated with those extrapolations is discussed and is found to be exacerbated by small data sets and inadequate data availability. Specific examples are provided that involve asbestos-induced mesothelioma and leukemia caused by benzene exposure.

Actuarial Analysis↗

Unusual myocardial (myostromal) "repair" in cardiac transplant patient.

A 57-year-old man received a cardiac allograft for severe ischemic heart disease. His endomyocardial biopsy at eight weeks postoperatively showed a focus of unusual myocardial morphology characterized by small diameter myocytes associated with loose, myxoid appearing stroma and a myocytic mitotic figure. We feel this may represent a unique type of myocardial repair.

Biopsy↗