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Biomedical subjects

J B Morris

Publications and source records attributed to J B Morris.

At least 37 records · Page 2Linked to original sources
PubMed1998

Application of a hybrid computational fluid dynamics and physiologically based inhalation model for interspecies dosimetry extrapolation of acidic vapors in the upper airways.

This study provides a scientific basis for interspecies extrapolation of nasal olfactory irritants from rodents to humans. By using a series of short-term in vivo studies, in vitro studies with nasal explants, and computer modeling, regional nasal tissue dose estimates were made and comparisons of tissue doses between species were conducted. To make these comparisons, this study assumes that human and rodent olfactory epithelium have similar susceptibility to the cytotoxic effects of organic acids based on similar histological structure and common mode of action considerations. Interspecies differences in susceptibility to the toxic effects of acidic vapors are therefore assumed to be driven primarily by differences in nasal tissue concentrations that result from regional differences in nasal air flow patterns relative to the species-specific distribution of olfactory epithelium in the nasal cavity. The acute, subchronic, and in vitro studies have demonstrated that the nasal olfactory epithelium is the most sensitive tissue to the effects of inhalation exposure to organic acids and that the sustentacular cells are the most sensitive cell type of this epithelium. A hybrid computational fluid dynamics (CFD) and physiologically based pharmacokinetic (PBPK) dosimetry model was constructed to estimate the regional tissue dose of organic acids in the rodent and human nasal cavity. The CFD-PBPK model simulations indicate that the olfactory epithelium of the human nasal cavity is exposed to two- to threefold lower tissue concentrations of a representative inhaled organic acid vapor, acrylic acid, than the olfactory epithelium of the rodent nasal cavity when the exposure conditions are the same. The magnitude of this difference varies somewhat with the specific exposure scenario that is simulated. The increased olfactory tissue dose in rats relative to humans may be attributed to the large rodent olfactory surface area (greater than 50% of the nasal cavity) and its highly susceptible location (particularly, a projection of olfactory epithelium extending anteriorly in the dorsal meatus region). In contrast, human olfactory epithelium occupies a much smaller surface area (less than 5% of the nasal cavity), and it is in a much less accessible dorsal posterior location. In addition, CFD simulations indicate that human olfactory epithelium is poorly ventilated relative to rodent olfactory epithelium. These studies suggest that the human olfactory epithelium is protected from irritating acidic vapors significantly better than rat olfactory epithelium due to substantive differences in nasal anatomy and nasal air flow. Furthermore, the general structure of the hybrid CFD-PBPK model used for this study appears to be useful for target tissue dosimetry and interspecies dose comparisons for a wide range of inhaled vapors.

Acrylates↗
PubMed1998

Electroencephalographic and psychometric differences between boys with and without attention-deficit/Hyperactivity disorder (ADHD): a pilot study.

Attention-Deficit/Hyperactivity Disorder (ADHD) is reported to have an incidence of 3-5%, and is associated with a variety of interpersonal, academic, and social problem behaviors. There is controversy as to whether ADHD is a learned behavioral or brain dysfunction. Research has explored a variety of measures to assess behavioral and brain dysfunctions in this population, with no consistent and clearly diagnostic results. We investigated whether a new psychometric and a new electroencephalographic procedure would clearly differentiate ADHD. The psychometric was based on DSM-IV criteria and the EEG measure was based on the assumption that ADHD interferes with cognitive transition from one discrete task to another. Parents of four ADHD boys (ages 8-12) and four age- and interest-matched non-ADHD boys completed the ADHD Symptom Inventory, while their sons' EEG was monitored during viewing of a video and reading of a book. For the ADHD boys, this was repeated a second time, 3 months later, to assess test-retest reliability. Both the psychometric and the EEG measures clearly differentiated the two samples (p's < .01) with no overlap in scores, were reliable over 3 months (r = .87), and were significantly correlated with one another (r = .85). While a small sample size, these robust, related and reliable findings suggest that both the psychometric and the psychophysiological EEG measures deserve further replication and exploration.

Attention Deficit Disorder with Hyperactivity↗
PubMed1998

Splenic vein thrombosis secondary to focal pancreatitis diagnosed by endoscopic ultrasonography.

We report splenic vein thrombosis diagnosed by endoscopic ultrasonography (EUS) after the failure of extracorporeal ultrasound and contrast enhanced computed tomography to establish the diagnosis in a patient with gastrointestinal bleeding and anemia. Subsequent preoperative magnetic resonance imaging revealed findings of retroperitoneal fibrosis and confirmed the EUS findings. Splenic vein thrombosis is a well-known cause of gastrointestinal bleeding and splenomegaly; pancreatitis and pancreatic tumors are its most common underlying causes. Abdominal ultrasound and computed tomography are frequently used to diagnose splenic vein thrombosis. We discuss the use of EUS for diagnosis of vascular anomalies in the gastrointestinal tract and the association of splenic vein thrombosis, retroperitoneal fibrosis, and pancreatitis.

Endosonography↗
PubMed1997

Dosimetry, toxicity and carcinogenicity of inspired acetaldehyde in the rat.

Acetaldehyde is a ubiquitous air pollutant. It is an important industrial chemical and is also produced during the combustion of wood or tobacco. In smoky indoor atmospheres concentrations of the aldehyde may reach 100 ppb. Acetaldehyde is metabolized to acetate (releasing hydrogen ion) by aldehyde dehydrogenase a process which, in most tissues, represents a detoxification pathway. In vitro, acetaldehyde forms DNA-DNA and DNA-protein crosslinks. It is a clastogen, and inducer of sister chromatid exchanges, and is, perhaps, a weak mutagen. Inhalation exposure to 1000 ppm may induce DNA-protein crosslink formation in nasal tissues in the rat in vivo. Inhalation toxicity studies have shown acetaldehyde vapor causes chronic tissue injury and tumor formation in nasal tissues at exposure concentrations of 750 ppm or higher, with nasal olfactory mucosa being more sensitive than respiratory mucosa. Dosimetric estimates suggest that marked tissue injury and carcinogenicity occurs only at inspired concentrations which are sufficiently high to overwhelm nasal aldehyde dehydrogenase detoxification capacity. The induction of squamous cell carcinomas in the respiratory mucosa by acetaldehyde displays many analogies to the induction of squamous cell carcinomas by formaldehyde. For both vapors, non-linear concentration response relationships are observed for DNA-protein crosslink formation, tissue injury, and carcinogenicity, suggesting these responses are associated. For both vapors it is possible to document an exposure concentration that produces nasal respiratory epithelial injury without increasing tumor incidence, suggesting that for respiratory mucosa-derived tumors, exposure to non-cytotoxic concentrations may pose limited carcinogenic risk. In addition to squamous cell carcinomas of the respiratory epithelium, acetaldehyde exposure also results in nasal olfactory injury and tumors (adenocarcinomas) in the rat. The studies performed to date have not demonstrated a no observable effect level for these responses, therefore, the precise role of cytotoxicity and regenerative cell proliferation in the carcinogenic process in olfactory tissues can not be evaluated. Acetaldehyde metabolism via aldehyde dehydrogenase results in the formation of two hydrogen ions. The olfactory mucosa is quite sensitive to acid and dosimetric estimates suggest that the intracellular acid production rates that may occur in olfactory mucosa during acetaldehyde exposure may be sufficiently high to cause tissue damage. Such acid-induced tissue damage may enhance the genotoxic and tumorigenic potential of acetaldehyde in olfactory mucosa, and may, therefore, represent an important process in the production of tumors in this tissue.

Acetaldehyde↗
PubMed1997

Uptake of acetaldehyde vapor and aldehyde dehydrogenase levels in the upper respiratory tracts of the mouse, rat, hamster, and guinea pig.

Acetaldehyde is a ubiquitous indoor and outdoor air pollutant. This vapor is a respiratory tract irritant and a rodent inhalation carcinogen. The current study was aimed at examining the upper respiratory tract (URT) deposition efficiency for this vapor at inspired concentrations of 1, 10, 100, or 1000 ppm in four rodent species: B6C3F1 mouse, Sprague-Dawley rat, Syrian hamster, and Hartley guinea pig. For measurement of vapor uptake, the URT was isolated in urethane-anesthetized animals via insertion of a polyethylene cannula in the trachea such that its tip lay at the larynx. Uptake was measured under constant velocity unidirectional inspiratory flow at flow rates of approximately 50, 100, 200, and 300% of the predicted minute ventilation of each species and also under pseudo-cyclic flow (sinusoidal flow at 100% of the predicted minute ventilation with a constant 7 ml/min bleed for analysis). In addition, aldehyde dehydrogenase (AldDH) activities were measured in whole nasal tissue homogenates from each species for comparative purposes. In all species a high-affinity (Km < 0.2 mM), low-capacity AldDH isozyme was observed. In the mouse, hamster, and rat, a low-affinity (Km > 10 mM), high-capacity isozyme was observed; this isozyme was not observed in nasal tissue homogenates of the guinea pig. In all species, URT deposition efficiency was strongly dependent on the inspired concentration, with uptake being two- to three-fold more efficient at inspired concentrations of 1 or 10 ppm than at 1000 ppm. For example, at flows approximating the twice-minute ventilation rate URT uptake efficiency averaged 43, 49, 28, and 43% in the mouse, hamster, rat, and guinea pig, respectively, at an inspired concentration of 10 ppm, compared to 27, 14, 16, and 6% at an inspired concentration of 1000 ppm. Species differences were observed in uptake efficiency. At an inspired concentration of 1000 ppm a two-factor analysis of variance followed by a Newman-Keuls test revealed that uptake was significantly higher in the mouse, rat, and hamster than in the guinea pig. In contrast, at 10 ppm uptake was significantly lower in the rat than in any other species. Thus, the rank order of these species on the basis of ability to scrub acetaldehyde from the airstream differed at high compared to low inspired concentrations. The documentation of greatly differing deposition efficiencies as well as differing relative dosimetric relationships among species at high compared to low exposure concentrations highlights the potential complexities of quantitative extrapolation of high-concentration rodent inhalation toxicity data.

Acetaldehyde↗
PubMed1997

Accumulation of manganese in rat brain following intranasal administration.

Manganese chloride (50-800 micrograms) was injected unilaterally into the right nostril of rats and its accumulation in the central nervous system (CNS) was monitored. Brain manganese levels were elevated in a dose-dependent, time-dependent, and tissue-dependent manner. Elevated levels of manganese were detected in the right olfactory bulb and olfactory tubercle within 12 hr after instillation and remained elevated for at least 3 days. As little as 100 micrograms of manganese chloride was sufficient to increase brain manganese levels. No changes were detected on the left side of the brain. The manganese content of the striatum, the target site for manganese neurotoxicity, was unchanged following acute administration, but was elevated when two injections were made 1 week apart. These results suggest that air-borne manganese can be retrogradely transported along olfactory neurons to the CNS and can reach deeper brain structures under appropriate exposure conditions.

Administration, Intranasal↗
PubMed1997

Preoperative and postoperative imaging for colorectal cancer.

Management and survival in colorectal cancer are dictated by the extent of the disease at the initial diagnosis. Technological advances over the past 25 years have improved the ability to accurately preoperatively stage these lesions and detect recurrence. This article reviews the focus on the utility of computerized tomography, magnetic resonance, endoscopic ultrasound, and newer imaging methods including PET scan and monoclonal antibodies in the management of colorectal carcinoma.

Colorectal Neoplasms↗
PubMed1996

A parallelogram approach for safety evaluation of ingested acetaldehyde.

Route-specific carcinogenicity data are often lacking for compounds of regulatory importance. Acetaldehyde (AA), for example, a natural constituent in foods, is a rodent carcinogen via the inhalation route, but oral carcinogenicity data are not available. In the absence of such data, a parallelogram approach can be used to estimate the oral carcinogenic potency of this chemical. The relative potency of AA to the structurally related compound formaldehyde (FA) in the nose and the relative potency of FA in the nose and stomach serve as the basis for estimating the potency of AA in the stomach. On a dosimetric basis, inhaled AA is 14- to 35-fold less potent than FA in producing nasal DNA-protein crosslinks (DPX), subchronic tissue injury, and tumors. Ingested AA is also considerably ( approximately 5-fold) less potent than FA in producing gastric injury and DPX. Compared to the nose, the stomach is 10- to 60-fold less sensitive to both AA- and FA-induced DPX and subchronic tissue injury. The parallelogram approach will not supplant long-term oral carcinogenicity studies with AA; however, the consistent pattern of decreased sensitivity of acetaldehyde compared to formaldehyde, lower sensitivity of the stomach to the nose, and the lack of gastric tumorigenicity of orally ingested formaldehyde strongly suggests that ingested acetaldehyde is not likely to be carcinogenic. Successful estimation of the carcinogenic potency of ingested glutaraldehyde, for which chronic oral and inhalation data are available, provides further support that the parallelogram approach can provide a reasonable estimate of the carcinogenic potency of closely related aldehydes, such as AA.

Acetaldehyde↗
PubMed1996

Pulmonary activation and toxicity of cyclopentadienyl manganese tricarbonyl.

Cyclopentadienyl manganese tricarbonyl (CMT) produces acute pulmonary injury following cytochrome P450 mixed-function oxidase (CYP450) activation. The current studies were designed to characterize the role of hepatic and/or pulmonary CMT activation and the subsequent pneumotoxicity of this compound following subcutaneous injection in the male Sprague-Dawley rat. Both pulmonary and hepatic tissues were capable of CYP450-dependent CMT metabolism in vitro. Phenobarbital pretreatment, which induced hepatic but not pulmonary CMT metabolism, protected against CMT-depended pneumotoxicity suggesting escape of an active CMT metabolite from the liver is not responsible for the pneumotoxic response. Animals were also pretreated with either m-xylene or 3-methylindole, each of which reduce CMT metabolism in the lung but not in the liver. These pretreatments also reduced CMT-dependent pulmonary damage. Protection against toxicity by two compounds that inhibit pulmonary but not hepatic CMT metabolism provides strong evidence that CMT-induced pneumotoxicity is due to the activation of CMT within the lungs. Histopathological studies revealed that CMT induced an alveolar injury without apparent damage to the bronchiolar airways. Based on this pattern of injury, studies were performed with freshly isolate alveolar type II (ATII) cells as these cells are thought to contain significant CYP450 activity. However, CMT metabolism was not detectable in ATII cells in vitro. Although CMT was cytotoxic to ATII cells in vitro, this response was not inhibited by metyrapone indicating CYP450 activation was not involved in the in vitro phenomenon. Together these data suggest in situ activation of CMT is necessary for the alveolar toxicity of this compound; however, activation does not occur in ATII cells.

Animals↗
PubMed1996

Gastroparesis: a potential pitfall of laparoscopic Nissen fundoplication.

We report a case of a patient who developed gastroparesis after laparoscopic Nissen fundoplication. The development of postoperative gastroparesis after either an open or laparoscopic Nissen fundoplication is uncommon but may result in significant morbidity. With greater numbers of laparoscopic fundoplications being performed, the complication of gastroparesis may be noted more frequently.

Adult↗
PubMed1995

Abdominal lymphangioma masquerading as a pancreatic cystic neoplasm.

Lymphangiomas are congenital abnormalities of the lymphatics that occur predominantly in the head and neck, most often in children. We present an unusual case of a middle-aged man who had a large septated cystic lesion adherent to the pancreas that could not be differentiated from a pancreatic cystic neoplasm despite analysis by ultrasound, computed tomography, magnetic resonance imaging, or percutaneous needle aspiration. The correct diagnosis was established only via laparotomy and subsequent pathologic interpretation. Although lymphangiomas are rare, they should be included in the differential diagnosis of pancreatic cystic neoplasms.

Biopsy↗
PubMed1994

Effects of m-xylene on rat nasal cytochrome P450 mixed function oxidase activities.

The effect of m-xylene on the rat nasal cytochrome P450 (P450) mixed function oxidase system was analyzed in vitro utilizing microsomes isolated 2, 12, and 24 h following intraperitoneal administration of this solvent in vivo. For comparative purposes, pulmonary and hepatic activities were also measured. Benzyloxyresorufin O-deethylation (BROD) and ethoxyresorufin O-deethylation (EROD), catalytic activities linked with P450 isozymes IIB1 and IA1, respectively, were inhibited in nasal tissue at all times following m-xylene administration. Pulmonary tissue mimicked this m-xylene-dependent inhibition of BROD activity but did not display significant inhibition of EROD activity. In contrast, m-xylene caused a dramatic induction of both BROD and EROD activity in hepatic tissue. The metabolism of a third P450 substrate, cyclopentadienyl manganese tricarbonyl (CMT), was also analyzed. m-Xylene caused significant inhibition of CMT metabolism at all time points in both nasal and pulmonary microsomes but was without effect on hepatic microsomal metabolism of this compound. These data show an inhibitory effect of m-xylene on rat nasal and pulmonary but not hepatic cytochrome P450-dependent metabolism.

Animals↗
PubMed1994

Bioavailability to rats of iron from fortified grain amaranth.

In this study, fortified and unfortified grain amaranth seed flour diets and a FeSO4-fortified casein diet (used as a control) were evaluated for their iron (Fe) bioavailability. NaFeEDTA, ferrous fumarate, and FeSO4-fortified grain amaranth were fed to growing Sprague-Dawley weaning male rats. Iron intake, hemoglobin iron (HbFe) gain, Fe availability, total iron binding capacity (TIBC), serum iron, non-haem liver iron and red bloodcell volume (RBV) were determined, and the values were compared with those of the FeSO4-fortified casein diet control. Ferrous fumarate fortified diets gave consistently high values for all these parameters, compared with consistently low values for the amaranth diet without iron fortification. Relative biological values (RBVs) were 0.40, 1.55, 1.75, 1.67 and 1.00 for animals fed on an unfortified amaranth diet, and diets fortified with NaFeEDTA, ferrous fumarate, FeSO4 and casein fortified with FeSO4, respectively. Using FeSO4-fortified casein as control, ferrous fumarate gave a superior RBVs (1.75 vs. 1.00). The RBVs, of the unfortified cereal diets were 40% that of the control, perhaps suggesting low iron absorption from the amaranth cereal. Based on the results of this study, amaranth cereal can be considered an idea food vehicle for iron fortification. The iron fortification of choice is ferrous fumarate.

Animals↗
PubMed1994

Esophageal disease in the elderly patient.

Disorders of the esophagus in elderly patients are usually associated with the classic symptoms of dysphagia, regurgitation, chest pain, and heartburn. Pulmonary complaints as a result of undiagnosed esophageal disease are common in this age group. Diagnosis is often delayed because symptoms are attributed to underlying cardiac and pulmonary disease. Elderly patients are more susceptible to the complications of aspiration and malnutrition that often accompany inadequately treated esophageal disease; therefore, prompt and aggressive treatment is indicated. Criteria for surgical intervention in esophageal disease do not change with age. Properly selected elderly patients tolerate esophageal surgery well. Age alone should not constitute a contraindication to surgery of the esophagus.

Aged↗
PubMed1994

Acute NO2 exposure alters inflammatory cell activation and particle clearance in silica-injected mice.

Previous work indicates that exposure to nitrogen dioxide (NO2) at different stages of silica-induced acute inflammation alters the outcome of lung injury. C57BI/6 mice were injected intratracheally (IT) with 2.0 mg silica particles (SI) and subsequently exposed to 20 ppm NO2 (or filtered air) within 2 or 24 h after SI. The present study demonstrates that exposure of mice to NO2 within 2 h after silica injection during acellular lung injury (increased alveolar protein, albumin, lactate dehydrogenase) resulted in increases in intraalveolar and interstitial polymorphonuclear leukocytes (PMNs) as well as more advanced granulomas on d 14, 30, and 60. In contrast, exposure of mice to NO2 24 h after silica during marked lung injury and inflammatory cell influx resulted in a less severe inflammatory reaction with fewer interstitial and alveolar PMNs and decreased size and number of pulmonary granulomas. NO2 exposure 2 or 24 h after SI appeared to increase in the lavage fluid levels of lysosomal enzymes and at the same time decrease levels of PMN chemotactins. Moreover, exposure to NO2 24 h after SI significantly decreased SI accumulation in the mediastinal lymph nodes. These data suggest that NO2 modulation of SI lung injury may be due, in part, to changes in inflammatory cell activation/influx and/or altered particle disposition within the lung. These effects are dependent upon the inflammatory status of SI exposed lungs at the time NO2 is administered.

Animals↗
PubMed1994

Incidental laparoscopic repair of a spigelian hernia.

A case of an incidental spigelian hernia discovered during a laparoscopic pelvic lymph node dissection for prostatic carcinoma is described. The proposed management of this unusual finding is reviewed.

Adenocarcinoma↗
PubMed1993

Advances in biologically based models for respiratory tract uptake of inhaled volatiles.

Physiologically based pharmacokinetic models for volatile organic chemicals typically describe the respiratory tract as a single compartment in which chemicals in the alveolar air space and the arterial blood are in instantaneous equilibrium. These models also assume that the distribution of chemical in the air-stream is uniform throughout the respiratory tract and that uptake is significant only in the alveolar region. A functional role for the upper respiratory tract in the uptake of volatile chemicals has been largely ignored. While these models have worked well for chemicals with low aqueous solubility in biological fluids, systemic uptake of highly soluble volatiles is overestimated. Thus, there is a significant effort to describe the critical determinants for uptake of soluble chemicals and to formulate models with more biologically relevant descriptions of respiratory tract structure and function. Investigators have addressed this problem from several viewpoints. Airflow patterns in the respiratory tract, regional metabolism, diffusion-dependent uptake, and the cyclic nature of respiration are now being incorporated into current models. Use of dosimetric models that incorporate relevant biology for inhaled chemicals will ultimately result in more meaningful human risk assessments.

Administration, Inhalation↗