Search PubMed⌕ Search

Biomedical subjects

J B Morris

Publications and source records attributed to J B Morris.

At least 55 records · Page 3Linked to original sources
PubMed1993

A physiologically based pharmacokinetic model for nasal uptake and metabolism of nonreactive vapors.

A PB-PK model has been developed for nasal nonreactive vapor uptake in the F344 rat which incorporates nasal enzyme distribution as well as nasal airflow patterns. Nasal tissue is separated into respiratory and olfactory mucosal areas with each area containing mucus, epithelial, and submucosal compartments. Metabolic activities are distributed among the compartments in accordance with published histochemical data, and intercompartmental transfer rate constants are based on molecular diffusivity. Two airflow paths are assumed: a lateral/ventral path which passes over only respiratory mucosa and a dorsal medial path which passes over both respiratory and olfactory mucosa. This model was fit to F344 rat nasal uptake data obtained for five vapors: acetone (an unmetabolized vapor), isoamyl alcohol (alcohol dehydrogenase substrate), ethyl acetate (carboxylesterase substrate), and o-xylene and bromobenzene (mixed function oxidase substrates). These vapors cover a wide span of uptake values ranging from a fractional uptake of less than 0.01 for xylene to 0.80 for isoamyl alcohol. The model accurately predicted the fractional uptake of these vapors, the maximal deviation between actual and predicted values being 0.04. The best fit for the data was obtained assuming: (1) an asymmetric blood flow pattern (with the majority of the blood flow being apportioned to the respiratory mucosa), and (2) only a small fraction of the total airflow (8%) following the dorsal medial pathway and penetrating to the olfactory mucosa. Since only a small fraction of the inspired air passes over the olfactory mucosa, a site with high metabolic activity, an inspiratory flow rate dependence on inspired vapor metabolism results. At low flows, olfactory metabolism is limited by low vapor delivery to that site, an effect that does not occur at high flows. This highlights the potential importance of regional nasal airflow and enzymatic activity patterns in influencing uptake and metabolism of inspired vapors and indicates the need for physiologically relevant models incorporating these factors.

Animals↗
PubMed1993

Somatostatin attenuates ischemic intestinal injury.

Pancreatic-derived proteases play a central role in the pathogenesis of ischemic intestinal injury. We postulated that exocrine blockade by pretreatment with a long-acting somatostatin analogue, octreotide acetate, would attenuate ischemic mucosal injury. Sprague-Dawley rats received subcutaneous octreotide (10 micrograms/kg/d) for 6 days by means of surgically implanted infusion ports. In a group of sham control rats, splanchnic blood flow (portal vein Doppler measurement) and duodenal trypsin activity (p-toluene sulfonyl-L-arginine methyl ester assay) were determined. In a separate experiment, pretreated animals were subjected to 60 minutes of superior mesenteric artery ischemia alone or followed by 30 minutes of reperfusion. Gross extent of hemorrhagic necrosis and microscopic injury (rank analysis) were assessed by a blinded observer. Pretreatment with octreotide reduced intraluminal duodenal trypsin activity by 46% without affecting portal blood flow. However, octreotide pretreatment significantly attenuated the microscopic depth of injury during ischemia and the extent of gross injury during reperfusion. It appears that somatostatin may have an adjuvant role in the prevention or progression of intestinal ischemic injury.

Animals↗
PubMed1993

Home parenteral nutrition after near total enterectomy.

Six patients with extreme short bowel syndrome (4.2 +/- 4.9 cm of residual small bowel) were provided home parenteral nutrition (HPN) for 14,397 days. The average age at onset of HPN was 38 years (18-64 years). Patients maintained body weight at 97% of ideal (86-112%) with mean serum albumin of 3.7 +/- 0.6 g/dL (normal 3.5-5.8 g/dL), serum transferrin of 341 +/- 104 mg/dL (normal 200-400 mg/dL), and mean serum pre-albumin of 27.5 +/- 12.6 mg/dL (normal 16.6-43 mg/dL). Hospital admission for HPN-related complications was required 10.3 times/patient for a total of 864 hospital days and was catheter related in 71% of episodes. Catheter sepsis occurred once per 436 catheter days and required catheter removal in only 33% of instances. Five patients were able to resume an oral diet, five had returned to work or school, and three were married with family. HPN allowed return to a quality productive life with acceptable morbidity following catastrophic massive bowel resection.

Adolescent↗
PubMed1993

Safe laparoscopic cholecystectomy without intraoperative cholangiography.

The role of intraoperative cholangiography during laparoscopic cholecystectomy is controversial. Between July 1990 and June 1991, 82 of 84 consecutive patients (mean age, 46 +/- 14 years) with symptomatic cholelithiasis successfully underwent laparoscopic cholecystectomy with only one intraoperative cholangiogram. Fourteen patients underwent preoperative endoscopic retrograde cholangiopancreatography (ERCP) for suspected choledocholithiasis of which two demonstrated common duct stones and underwent sphincterotomy. Complications of laparoscopic cholecystectomy included one each of bilioma, umbilical wound infection, epigastric trocar site hernia, and flank seroma. No major bile duct or vascular injury occurred. Follow-up data was available on all patients for a mean of 7.4 months (range, 3-13 months). Three patients developed symptoms suggestive of biliary tract disease at 0.25, 4, and 8 months postoperatively. Symptoms spontaneously resolved in all three; all underwent ERCP, of which two were normal and one unsuccessful. We have concluded that (a) a meticulous operative dissection resulted in no major bile duct or vascular injury; (b) patients with unsuspected choledocholithiasis preoperatively rarely developed postoperative symptoms; and (c) the practice of laparoscopic cholecystectomy can be conducted safely without intraoperative cholangiography.

Adult↗
PubMed1992

Upper respiratory tract deposition of inspired acetaldehyde.

Inhalation exposure of rodents to high concentrations of acetaldehyde produces lesions in the upper respiratory tract (URT, all regions of the respiratory tract anterior to and including the larynx). Information on the inhalation dosimetric relationships for this vapor are needed for a comprehensive understanding of its inhalation toxicity. Toward this end, uptake of acetaldehyde was measured in the surgically isolated URT of the urethane-anesthetized male F344 rat under unidirectional (50, 100, 200, or 300 ml/min) and cyclic (100 ml/min) flow conditions at inspired concentrations of 1, 10, 100, or 1000 ppm. Under all flow conditions URT deposition efficiency was strongly dependent on inspired concentration. URT deposition efficiency (under cyclic flow) averaged 76, 48, 41, and 26% at 1, 10, 100, and 1000 ppm, respectively. Nasal acetaldehyde dehydrogenase activity averaged 1.2 micrograms/min. Absolute acetaldehyde deposition rates (micrograms/min) at 100 and 1000 ppm exceeded this activity by 5- to 100-fold, suggesting a possible mechanism for the reduced deposition efficiency at high concentrations. URT deposition under unidirectional flow was strongly dependent on the inspiratory flow rate. The effect of flow rate on deposition was reasonably predicted by the mass-transfer model of Aharonson et al. (J. Appl. Physiol. 37, 654-657, 1974). The uptake coefficients determined from the unidirectional flow studies were used to predict uptake under cyclic flow by integration of the model. The predicted cyclic deposition efficiencies differed from the observed efficiencies by 2.3 +/- 4.3% (mean +/- SEM), suggesting this model might provide a reasonable first approximation for acetaldehyde uptake under cyclic breathing conditions.

Acetaldehyde↗
PubMed1992

Silica-induced pulmonary inflammation and fibrosis in mice is altered by acute exposure to nitrogen dioxide.

The biologic impact of consecutive exposures to two environmental pollutants was examined in mice exposed to silica crystals (SI) by intratracheal (IT) injection followed by an inhalation exposure to nitrogen dioxide (NO2). C57Bl/6 mice received an IT injection of 2 mg SI or sterile saline (SAL) followed by a 2-h inhalation exposure to NO2 at 20 ppm either within 2 h of or 24 h after SI instillation. During acute inflammation (d 3 postsilica), mice exposed to NO2 at either time showed a dramatic and significant reduction in the number of lavaged alveolar neutrophils (PMN) when compared to silica/air-exposed mice. Animals exposed to NO2 24 h after silica also evidenced significant decreases in levels of lavage albumin and lactate dehydrogenase (LDH) 3 d after silica, as well as significant decreases in hydroxyproline content of the lung 30 and 60 d postsilica injection when compared to silica/air-exposed animals. NO2 administration 24 h after silica appeared to shift the appearance of PMN in the lung from d 3 to d 14, but did not otherwise alter chronic cellular inflammation. These data suggest that the marked neutrophil response and collagen deposition induced by SI can be modulated by NO2 exposure and that the time of oxidant gas exposure after silica administration is critical to this modulation.

Acute Disease↗
PubMed1992

Surgical jejunostomy in aspiration risk patients.

One hundred patients underwent laparotomy for independent jejunal feeding tube placement. Neurologic disease was present in 50%, and obtundation (28) and oropharyngeal dysmotility (25) were the most common indications for enteral feeding. The post-pyloric route was chosen because of aspiration risk in almost all (94%) patients. Postoperative (30-day) mortality rate was 21%, because of cardiopulmonary failure in most (18). One death resulted directly from aspiration of tube feeds. Two surgical complications required reoperation: one wound dehiscence and one small bowel obstruction. Four wound infections occurred. Two patients underwent reoperation after tube removal, and four tubes required fluoroscopically guided reinsertion for peritubular drainage (2), removal (1), and occlusion (1). Aspiration pneumonia was present in 18 patients preoperatively and in eight postoperatively. None of the patients with feeding-related preoperative aspiration pneumonia (13) had a recurrence while fed by jejunostomy. Three patients developed postoperative aspiration pneumonia before initiation of jejunostomy feedings. Jejunostomy may be performed with low morbidity rate and substantial reduction of feeding-related aspiration pneumonia, and is the feeding route of choice in aspiration risk patients.

Adult↗
PubMed1992

Acute esophageal obstruction: a unique presentation of a giant intramural esophageal leiomyoma.

We report the case of a 33-yr-old man who presented with an acute incomplete esophageal obstruction, mimicking food impaction, who was found to have a giant intramural esophageal leiomyoma. The leiomyoma was successfully removed through a longitudinal esophagotomy. This is the first report of a nonpedunculated intramural esophageal leiomyoma presenting as an acute esophageal obstruction.

Adult↗
PubMed1992

Laparoscopic-guided jejunostomy.

The proximal jejunum is the preferred site for long-term enteral access in the patient at risk for aspiration. Herein we describe a laparoscopic technique for the creation of a feeding tube jejunostomy. This minimally invasive approach is an alternative for patients requiring chronic postpyloric enteral feeding.

Humans↗
PubMed1991

Laser-excited atomic fluorescence in a flame as a high-sensitivity detector for organomanganese and organotin compounds following separation by high-performance liquid chromatography.

The coupling of a high-performance liquid chromatograph with a sensitive and selective laser-excited atomic fluorescence spectrometry (LEAFS) detector is described. In connection with this, a study of the signal and noise characteristics of instrumentation for dispersive, nondispersive, and front surface LEAFS is reported together with a comparison of the sensitivity and selectivity achieved with high-performance liquid chromatography (HPLC)-flame LEAFS, HPLC-ultraviolet (UV), and HPLC-continuum source excited flame atomic fluorescence spectrometry (AFC) instrumentation. The HPLC-flame LEAFS instrumentation was applied to an investigation of the Mn species responsible for (methylcyclopentadienyl)manganese tricarbonyl (MMT) toxicity in rats. The detection limits for various organomanganese species by HPLC-flame LEAFS ranged from 8 to 22 pg of manganese. Recovery of these compounds from rat urine varied between 80% and 100%, with a reproducibility of between 4% and 8% relative standard deviation. Preliminary data for the HPLC-flame LEAFS determination of toxic alkyltin compounds are reported.

Chromatography, High Pressure Liquid↗
PubMed1991

A critical analysis of the largest reported mass fecal occult blood screening program in the United States.

Fecal occult blood testing for the detection of colon cancer remains controversial. We performed a mass screening program from January 24, 1988, to February 19, 1988, with intensive media promotion, including 121 minutes of televised air time. A total of 5,000 primary practitioners were notified by mail. Hemoccult-II tests were distributed to 156,000 individuals; 55,051 (35%) were returned. Ninety-five percent of the respondents were informed of the program by television. A total of 3,375 persons (6%) tested positive for fecal occult blood; of these, 2,469 (73%) informed the center that they saw their physician to initiate a work-up. Information from physicians regarding work-ups was returned on only 1,356 (55%) patients. Diagnostic tests numbered 2,227 (1.6 tests per patient). However, 5% had no testing, 16% had a repeat Hemoccult only, and 35% had neither a barium enema nor colonoscopy performed. Thirty-six colorectal cancers and 212 polyps were identified. The predictive value (i.e., number of cancers per number of patients who tested positive) increased directly by decade. Thirty-three of 36 patients (92%) with cancer underwent either a barium enema or colonoscopy versus only 185 of 438 (42%) patients with a "negative" work-up. Cancers found were carcinoma in situ in 10 patients (29%), Dukes A in 12 (35%), Dukes B in 4 (12%), and Dukes C in 8 (24%); distant metastases were not found in any participant. Thirty-six percent of the tumors were located in either the right or transverse colon. We conclude that: (1) Screening identified early cancers. All were potentially curable and 64% were limited to the bowel wall. (2) Massive Hemoccult distribution was possible over a short interval, but patient and physician compliance was disturbingly low. (3) Total colonic evaluation is mandatory, since at least 36% of tumors were beyond the reach of the flexible sigmoidoscope. (4) Many work-ups were unnecessary (repeat Hemoccults) or inadequate, indicating a need for physician education.

Adult↗
PubMed1991

Deposition of dibasic esters in the upper respiratory tract of the male and female Sprague-Dawley rat.

Inhalation exposure of the male and female rat to high concentrations of a mixture of the dibasic esters dimethyl succinate (DMS), dimethyl glutarate (DMG), and dimethyl adipate (DMA) results in mild olfactory toxicity. This response is thought to be due to the in situ formation of acidic metabolites via nasal carboxylesterases. The current study was designed to provide inhalation dosimetric information for these vapors. Deposition of DMS, DMG, and DMA was measured in the surgically isolated upper respiratory tracts (URT) of ketamine-xylazine-anesthetized male and female rats under constant velocity flow conditions at a flow rate of 100 ml/min. Deposition of acetone was measured in both genders for comparative purposes. URT deposition efficiencies in excess of 98.3% were observed for DMS, DMG, and DMA in animals exposed to each vapor individually. No gender differences in deposition efficiency were observed for these vapors or for acetone. Deposition of DMS, DMG, and DMA was also measured in animals exposed to all three vapors simultaneously. Deposition efficiency under simultaneous exposure conditions ranged between 97.3 and 98.5%. These values were slightly lower (about 1%) than those obtained under individual exposure conditions (p less than 0.0001). The reduced deposition efficiency may have resulted from competitive inhibition of nasal metabolism due to the simultaneous presence of all three carboxylesterase substrate vapors in nasal tissues. If so, inhalation of dibasic ester vapors would be expected to inhibit the uptake of other carboxylesterase substrate vapors without influencing uptake of vapors which are not substrates for this enzyme. Such was observed in studies using DMS, ethyl acetate (the substrate vapor), and isoamyl alcohol (the nonsubstrate vapor). Specifically, simultaneous exposure to DMS markedly inhibited uptake of ethyl acetate without altering uptake of isoamyl alcohol. Gender differences were not observed in URT deposition of any of the six vapors used in the current study, DMS, DMG, DMA, ethyl acetate, isoamyl alcohol, or acetone, suggesting that gender differences in URT deposition may not be widespread among vapors. The high URT deposition efficiencies of the dibasic esters are consistent with the olfactory toxicity resulting from inhalation exposure to these vapors.

Acetates↗
PubMed1991

Deposition of acetone vapor in the upper respiratory tract of the B6C3F1 mouse.

Deposition of inspired acetone vapor in the surgically isolated upper respiratory tract (URT) of the anesthetized B6C3F1 mouse was measured under unidirectional constant velocity flow conditions for comparison with our previous studies on the rat, hamster and guinea-pig. Acetone metabolism in mouse nasal mucosal homogenates was examined in vitro. Acetone was metabolized by nasal homogenates via an NADPH-dependent pathway with a Vmax of 12 micrograms/min/whole nose and an apparent Km of 72 micrograms/ml. The enzyme responsible was not identified; however, metabolism was inhibited by pyrazole but not inhibited by metyrapone or incubation under nitrogen. URT deposition efficiency was measured at flow rates of 21, 33 or 70 ml/min and averaged 25, 20 and 14%, respectively; the efficiencies at each flow rate were significantly different (P less than 0.01). Deposition was measured at inspired concentrations ranging from 1,500-20,000 micrograms/liter. Deposition efficiencies were similar at all concentrations; the lack of saturation suggests this vapor was not metabolized when inspired. Kinetic analysis of the deposition data revealed that metabolism rates of inspired acetone were only a small fraction of that measured in vitro, suggesting that in vitro data could not be directly extrapolated to the in vivo setting. Deposition efficiency of acetone in the URT of the mouse was similar to that previously observed in the URT of the F344 rat, but was less efficient than that in the Sprague-Dawley rat and more efficient than that in the hamster or guinea-pig.

Acetone↗
PubMed1991

The impact of a resident-directed survey on the education curriculum of a university surgical training program.

Surgical training programs use various objective and subjective means to evaluate housestaff performance. However it is less clear how to assess the quality of the educational experience the program itself provides. This study examines the use of a resident-directed survey as a means of identifying and rectifying weakness in a surgical training curriculum. Multiple choice questionnaires covering each of 14 senior rotations were prepared by chief residents and distributed to all senior surgical residents in April 1989 (year I). The survey covered factors considered vital to resident education, including operative experience, input into preoperative and postoperative decisions, autonomy, and time demands, and an overall rating (OR) of the educational quality of the rotations. Responses were numerically graded: 1, appropriate; 0, fair; -1, inadequate (or "excessive" for the variable "time demands"). The results, which were presented and discussed at a departmental retreat that spring, prompted specific curriculum changes for the 1989-1990 academic year. An identical survey was conducted the next spring (year II). Major reorganizational changes were made in three of the four negatively rated rotations from year I. The OR for each of the rotations improved dramatically in year II (average increase of 0.64/rotation; p less than 0.05). None of the eight favorably rated rotations in year I suffered a reduction in OR as a result of the changes. Case load, intraoperative involvement, and input in both preoperative and postoperative decisions correlated most frequently with favorable ORs in both years. This study shows that a resident survey is an effective tool for critically assessing the education curriculum of a surgical training program.

Curriculum↗
PubMed1990

First-pass metabolism of inspired ethyl acetate in the upper respiratory tracts of the F344 rat and Syrian hamster.

Nasal tissues contain large amounts of carboxylesterase but its precise role in metabolism of inspired ester vapors is not known. The current study was aimed at quantitating the extent of metabolism of inspired ethyl acetate in the upper respiratory tract (URT) of the F344 rat and Syrian hamster. Ethyl acetate deposition was measured in the surgically isolated URT of these species under constant velocity unidirectional flow conditions. The degree of metabolism was estimated by mathematic modeling based on a simple venous-equilibration approach and by direct comparison of deposition efficiencies in naive and carboxylesterase-inhibited animals. Ethyl acetate deposition efficiencies averaged between 10 and 35% in the rat URT and 36 and 72% in the hamster. Carboxylesterase inhibition decreased deposition in both species. Both the modeling efforts and the direct comparisons between naive and inhibited animals indicated that significant amounts of the deposited ethyl acetate were metabolized in the URT of both species with the extent of metabolism being more pronounced in the hamster. Specifically, 40-65% of the deposited ethyl acetate was metabolized in the URT of the rat compared to 63-90% in the hamster. This first-pass metabolism (i) increased URT deposition efficiencies; (ii) led to production of high metabolite levels in URT tissues; and (iii) decreased the amount of parent ethyl acetate available for absorption into the bloodstream in the URT.

Acetates↗