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Biomedical subjects

T Hall

Publications and source records attributed to T Hall.

At least 91 records · Page 5Linked to original sources

Oxmetidine (H2 receptor antagonist) induced cytotoxicity in isolated rat hepatocytes.

Oxmetidine, a new and more potent analogue of the H2 receptor antagonist, cimetidine, was recently withdrawn from clinical trials because of associated hepatotoxicity. We investigated the potential hepatotoxicity of the drug in vitro and in vivo in the rat. In addition, we investigated, in in vitro experiments, the potential hepatoxicity of other gastric acid inhibitory drugs (cimetidine, ranitidine, omeprazole and nolinium bromide). In in vitro experiments, oxmetidine, at various concentrations, was added to isolated hepatocyte incubations and cytotoxicity was assayed by trypan blue exclusion. In in vivo experiments, oxmetidine was administered both i.p. and orally, and hepatotoxicity was assessed by serum biochemical measures (transaminases, alkaline phosphatase, 5' nucleotidase, gamma glutamyl transpeptidase) and liver histopathology. In the in vitro studies, the addition of oxmetidine to the hepatocyte incubations was associated with significant (P less than 0.001) dose and time dependent cytotoxicity. However, the in vivo experiments revealed no significant changes in serum biochemistry and no significant alterations in liver histopathology up to 72 h following the administration three different dosages of oxmetidine. Of the other gastric acid inhibitory drugs, only nolinium bromide was associated with significant (P less than 0.001) in vitro cytotoxicity. Our in vitro observations establish that oxmetidine is cytotoxic to isolated rat hepatocytes and suggest that nolinium bromide be further evaluated for potential hepatotoxicity.

Aniline Compounds↗

Radionuclide evaluation of liver transplants.

Orthotopic liver transplantation is now an established technique for treating patients with various forms of end stage liver disease. The number of centers performing the procedure is increasing and, as the number of transplant recipients in the population increases, many institutions performing nuclear medicine studies will be confronted with requests to evaluate these patients. While a variety of radionuclides are proving useful in this evaluation, the 99mTc iminodiacetic acid (IDA) compounds, particularly 99mTc diisopropyl IDA (DISIDA), will probably account for the majority of radionuclide evaluations of these patients because they are well suited to monitor both structural and functional changes of the graft. The primary application of radionuclide studies is focused in the postoperative period, when problems with the vascular and biliary anastomoses, rejection, infections, and bile leaks all produce alterations in radionuclide hepatobiliary studies. Abnormalities such as rejection and infection produce primarily functional, rather than structural changes and are not easily differentiated based upon the kinetics of 99mTc-DISIDA extraction and excretion by the liver, serial imaging and correlation with clinical data is necessary in such situations. Quantitative analyses of kinetic 99mTc IDA (DISIDA) studies and quantitative approaches with other compounds such as 99mTc galactosyl-neoglycoalbumin (NGA) may permit better assessments of relatively subtle changes in liver function in the posttransplant period.

Bile Duct Diseases↗

Effects of adsorbed water vapor on the adsorption rate constant and the kinetic adsorption capacity of the Wheeler kinetic model.

A recent trend in occupational safety and health has focused on the use of respiratory protective equipment to supplant engineering controls as the primary means of protecting workers from toxic substances. Respirator adsorbent cartridges have been demonstrated to have a finite capacity to adsorb toxic vapors. The knowledge of when this limit is approached or has been exceeded is crucial to the user. The Wheeler kinetic breakthrough model has been shown to describe accurately organic vapor penetration through beds of activated carbon. The model, however, does not account for competitive adsorption of water vapor or other organic vapors. The investigations reported here demonstrate the effect of adsorbed water vapor on the kinetic adsorption parameters (kinetic rate constant and kinetic saturation capacity) of the Wheeler equation. Adsorbent beds were equilibrated at varying concentrations of water vapor and then challenged with carbon tetrachloride vapor-laden air. Dry carbon had an initial rate constant of 62.5 s-1 and a kinetic adsorption capacity of 0.36 g of adsorbed CCl4/gram (g/g) of adsorbent. These parameters decreased in proportion to the amount of water vapor adsorbed, with the minimum predicted values occurring at 100% relative humidity. The minimum experimental value for the kinetic rate constant was 17.6 s-1, a decrease of 73% from the dry carbon values. The minimum predicted value for the kinetic adsorption capacity was 0.16 g/g, a decrease of 45%.

Adsorption↗

Primary liver tumors in children: comparison of CT and MR imaging.

A prospective study was performed at two institutions to determine the role of magnetic resonance (MR) imaging in the evaluation of primary pediatric liver tumors. The study compared the usefulness of MR imaging and computed tomography (CT) in providing a correct diagnosis, assessing resectability, and determining tumor recurrence in 23 children with liver tumors. The information obtained with both modalities was correlated with surgical data. The results indicate that the accuracy of MR imaging in helping to differentiate benign from malignant lesions is high and identical to that of CT, but not good enough to obviate surgical diagnosis. While all five hepatocellular carcinomas were correctly diagnosed preoperatively with both modalities, neither CT nor MR imaging could help differentiate these carcinomas from aggressive hepatoblastoma or primary hepatic lymphoma. MR imaging helped correctly predict tumor resectability in all 18 children with malignant hepatic tumors; in one, exact tumor extension was misjudged with CT. Postoperative MR studies suggested tumor recurrence in three children who had unremarkable CT examinations. Second-look surgery showed recurrent tumor in two and fibrosis with chronic inflammation at the surgical margin in the third child.

Adolescent↗

Expression of estramustine-binding protein (EMBP) and the proliferation-associated antigen Ki-67 in prostatic carcinomas.

The expression of EMBP and the proliferation-associated antigen Ki-67 was studied in in vitro cultured prostatic carcinoma cells and in tumor tissues removed by transurethral electroresection (TUR). EMBP was found to be expressed predominantly in the moderately differentiated carcinomas. A technique based on the immunohistochemical analysis of fine needle specimens was also evaluated. This technique is of potential interest in prospective studies and in monitoring the effect of therapy. Ki-67 was found to be expressed in the prostatic carcinoma cell line (DU-145) studied, as well as in TUR specimens. This antigen reflects the proliferative characteristics of the tumor and may prove useful with respect to prognostic information and choice of appropriate therapy.

Antibodies, Monoclonal↗

Elevation of serum aluminum in humans on a two-day sucralfate regimen.

Serum aluminum concentrations were determined in ten healthy subjects treated with phenytoin 500 mg and with sucralfate and phenytoin in a crossover fashion. Each subject received four 1,000-mg sucralfate tablets between 8 AM and 10 PM one day before the study, and this was repeated during the study day. A total of eight doses of sucralfate was administered over the two-day period. Serum samples were drawn at 0, 2, 4, 8, 12, 24, 32, and 48 hours after administration. The areas under the serum aluminum concentration-time curves before and after sucralfate (mean +/- SD) were 496.0 +/- 80.9 and 770.9 +/- 146.6 hr-ng/mL, respectively. This increase is statistically significant (P less than .01), indicating that serum aluminum levels are elevated even after two days of treatment with sucralfate. The results from this study are not in agreement with the only other report on this subject.

Adult↗

CT-findings in ARDS.

The CT features of 28 patients with ARDS are described. Diffuse lung consolidation, multifocal patchy involvement and lobar or segmental disease were observed. Large lung cysts as well as small cysts producing a "swiss-cheese" appearance of the parenchyma, were detected. These findings were not regularly appreciated on chest radiographs. The overall mortality of our 28 patients was 72.7% (22 out of 28). Patients with lung cysts showed a trend toward higher mortality (87.5% or 13 out of 16). Other unexpected findings were basilar lung abscesses and an empyema. In 15 out of 28 patients, CT scans provided additional information, not obvious on bedside chest radiographs and led to a change in management in five patients.

Adult↗

Surgical management of peritoneal dialysis catheters in children: five-year experience with 1,800 patient-month follow-up.

Currently at our institution more than 90% of the children with end-stage renal disease are managed with continuous ambulatory peritoneal dialysis (CAPD) in preference to hemodialysis until a successful transplant is accomplished. Recent refinements in CAPD catheters and dialysis techniques have greatly added to the many medical, psychological, and economic advantages of CAPD compared with chronic hemodialysis. Ninety-three patients less than 21 years of age underwent insertion of 167 peritoneal dialysis (PD) catheters over a 5-year period. A variety of PD catheters were used, including 121 (73%) double-cuff Tenckhoff catheters, 22 (13%) single-cuff, and 24 (14%) column disc catheters (Lifecaths, Physio-Control Corp, Redmond, WA). There were three (3%) noncatheter-related mortalities and minimal significant morbidity during the 1,819 patient-months of catheter use. Exit site infections (61%) and peritonitis (59%) were frequent but minor complications, occasionally requiring catheter replacement. Other noninfectious complications included abdominal hernias (42%), dialysis leaks (14%), distal cuff extrusion (11%), catheter obstruction (7%), and hydrothorax (2%). Forty-five of the 60 hernias (75%) were surgically repaired in patients while receiving CAPD. Persistent or recurrent peritonitis was common with Pseudomonas, Serratia, and fungal infections and often resulted in catheter removal and loss of the peritoneal dialysis membrane. Catheter survival for the double-cuff Tenckhoff was significantly better (P .005) than the single-cuff or Lifecath. Based on this experience we have found that using specific operative techniques for CAPD catheter placement and early surgical management for severe peritonitis reduces the incidence of complications and modality failure.

Adolescent↗

Determination of organic vapor respirator cartridge variability in terms of degree of activation of the carbon and cartridge packing density.

The protection provided by carbon-containing organic vapor respirator cartridges depends in part on the packing density of the carbon in the cartridges and its degree of activation. Large variations in these parameters could have significant effects on the service-life of respirator cartridges. Variability among commercially available organic vapor respirator cartridges was examined with regard to the following characteristics: the particle size distribution, amount of carbon and packing density of the carbon in the cartridges and the degree of activation of the carbon. The degree of activation was determined by measuring the maximum adsorption space and the structural constant of the carbon. These two parameters--Wo (cm3/g) and k (cal/M)-2--are constants in the Dubinin/Radushkevich (D/R) model from which physical absorption onto microporous adsorbents, such as activated carbon, are described. Respirator cartridges from three different suppliers were examined. Significant variability (11-40%) in the amount and the degree of activation of the carbon occurred between cartridges of different manufacturers, as well as among cartridges of an individual manufacturer.

Carbon↗

A critique of MSHA procedures for determination of permissible respirable coal mine dust containing free silica.

The literature in selected technical subject areas related to the Mine Safety and Health Administration's (MSHA) respirable mine dust control policy was critically reviewed. Specific topics included: (1) the technical aspects of respirable dust sampling, (2) the development of a sampling strategy and (3) currently used analytical techniques for free silica content of respirable coal mine dust. The 2.0 Lpm MSHA respirable dust sampling flow rate does not conform with published results which indicate that to simulate existing pulmonary particle deposition models, the sampling flow rate should range from 1.4 to 1.7 Lpm. MSHA's sampling strategy focuses on controlling respirable coal mine dust with both area and personal samples of workers in selected occupations or activities. Many uncertainties are encountered as area samples are used to estimate personal exposures. Although all of the analytical methods for crystalline free silica are sufficiently sensitive to be able to detect and quantitate free silica at environmentally significant concentrations, they are all plagued with similar difficulties. Analytical standards representing the various forms of silica are not available. Available analytical methods do not differentiate among polymorphs of silica. Recommendations are presented to resolve identified problem areas.

Air Pollutants, Occupational↗

Screening blood glucose values: effects of season and time of day.

Blood glucose screening results, obtained using two different screening procedures, are reported from two occupational groups. Post-prandial blood glucose levels were measured in 3346 subjects aged 45 years or more employed by the Greater London Council/Inner London Education Authority. In women, mean blood glucose levels were higher in the afternoon than the morning (p less than 0.05). Ninety-fifth centile levels were substantially higher in the afternoon in both sexes, though the differences were not constant in all age and sex sub-groups. In both sexes mean glucose levels were highest in the winter (December-February, inclusive), but seasonal variation did not significantly affect the proportion exceeding the ninety-fifth centile for the total population. In the Whitehall study, the blood glucose was measured in men, in the morning, 2h after a 50-g glucose load. Significant seasonal variation in mean blood glucose values occurred, with highest values in winter and lowest in spring (March-May, inclusive). However, there was no significant difference by season in the proportions exceeding the arbitrary cut-off levels of 7.8 and 11.1 mmol/l.

Adult↗

Comparison of continuous cycling peritoneal dialysis with continuous ambulatory peritoneal dialysis in children.

The clinical courses in 10 pediatric patients undergoing CAPD for 15.0 +/- 2.8 months and subsequently CCPD for 9.3 +/- 3.2 months were evaluated. During CAPD patients received four or five daily exchanges, and during CCPD five 2-hour nocturnal cycles over 10 hours plus a diurnal dwell. The only significant biochemical difference during CAPD compared with CCPD was the serum creatinine concentration (9.7 +/- 1.0 mg/dl vs 10.8 +/- 0.9 mg/dl, P less than 0.01). The peritonitis rate was one episode every 10.7 patient months during CAPD, compared with one episode every 8.5 patient months during CCPD. There were 21 episodes of exit site infection during CAPD versus 17 during CCPD. Mechanical complications included five ventral hernias in three patients and six peritoneal leaks in three patients during CAPD; two patients had two hernias and two patients had two peritoneal leaks during CCPD. Our results indicate adequate control of the biochemical abnormalities of uremia with CCPD, with the exception of the serum creatinine concentration.

Adolescent↗

Tumors undergoing rejection induced by monoclonal antibodies of the IgG2a isotype contain increased numbers of macrophages activated for a distinctive form of antibody-dependent cytolysis.

Monoclonal antibodies of the IgG2a isotype specifically inhibit the growth of human tumors in nude mice; tumors in mice given no antibody, an antibody of the IgG2a isotype that does bind to the tumor cells, or an antibody of the IgG2b isotype grow progressively. In the present work it is demonstrated that tumors of mice given the IgG2a antibody are essentially masses of necrosis, while tumors from the control mice are sheets of healthy tumor cells. Tumors of the treated mice, in comparison to controls, contain an increased number of macrophages, and these macrophages are activated for a distinct form of cytolysis dependent on antibodies of the IgG2a isotype. The data suggest that changes in the number and function of intratumoral macrophages are a major component of tumor destruction mediated by IgG2a antibodies.

Animals↗

Topologic mapping of protective and nonprotective epitopes on the variant surface glycoprotein of the WRATat 1 clone of Trypanosoma brucei rhodesiense.

Monoclonal antibodies were used in competitive antibody binding assays to define and map epitopes on the variant surface glycoprotein of the WRATat 1 clone of T. b. rhodesiense. By using a panel of 30 WRATat 1-specific monoclonal antibodies, 16 epitopes were defined that fall into four clusters, having 1, 1, 3, and 11 distinct epitopes respectively. All epitopes were easily classified as being 1) exposed uniformly on the surface of the trypanosome, 2) exposed only in the region of the flagellar pocket, or 3) "buried", based on the ability or inability of the monoclonal antibodies to bind living trypanosomes in a fluid phase immunofluorescence assay. Monoclonal antibodies that bind exposed surface epitopes are protective, whereas only three of seven that bind exclusively to flagellar pocket epitopes are protective. None of the nine monoclonal antibodies that recognize buried epitopes are protective. Also, antibody-mediated immunity to WRATat 1 trypanosomes is not associated with any particular subclass of antibody. The IgM, IgG1, IgG2a, IgG2b, IgG3, and IgA subclasses each contain examples of protective monoclonal antibodies.

Animals↗

Continuous ambulatory peritoneal dialysis catheters in children.

Based on clinical experience with 35 subjects younger than 21 years of age who underwent continuous ambulatory peritoneal dialysis (CAPD) during a two-year period at our institution, this procedure was found to be superior to hemodialysis in children because it allowed great freedom of activity and produced fewer complications requiring hospitalization. Moreover, CAPD appeared to be less expensive than hemodialysis, and no mortality or significant morbidity occurred during the 386 patient-months of catheter usage. Exit site infections, peritonitis, and abdominal hernias were the most common complications, often requiring minor surgical repairs. Using a specific operative technique for catheter placement and smaller volumes of dialysate during the first week after placement, these complications were minimized. Thus, CAPD is an effective, advantageous method for treatment of end-stage renal disease in children.

Adolescent↗