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Biomedical subjects

J R Stewart

Publications and source records attributed to J R Stewart.

At least 19 recordsLinked to original sources
PubMed1992

Evaluation of the toxicity, pathology, and treatment of cyclohexylmethylphosphonofluoridate (CMPF) poisoning in rhesus monkeys.

Cyclohexylmethylphosphonofluoridate (CMPF) is an organophosphate cholinesterase inhibitor with military significance. The purpose of these studies was 1) to determine the acute toxicity of CMPF in the male rhesus monkey, 2) to evaluate the efficacy of pyridostigmine (PYR) pretreatment plus atropine and oxime (2-PAM or H16) treatment, and 3) to evaluate the pathological consequences of acute poisoning. An i.m. LD50 of CMPF was estimated using an up-and-down dose selection procedure and 12 animals. The 48-h and 7-day LD50 was 46.6 micrograms/kg, i.m. In the protection experiments, pyridostigmine (0.3-0.7 mg/kg/24 h) was administered by surgically implanted osmotic minipumps for 3-12 days resulting in 21-65% inhibition of erythrocyte acetylcholinesterase activity. Animals were challenged with 5 x L50 CMPF (233 micrograms/kg) and treated with atropine (0.4 mg/kg) and either 2-PAM (25.7 mg/kg) or HI6 (37.8 mg/kg) at the onset of signs or 1 min after challenge. Osmotic pumps were removed within 30 min after agent challenge. Pyridostigmine, atropine, and either 2-PAM or H16 were completely effective against CMPF, saving ten of ten animals in each group. In comparison, three of five animals challenged with 5 x LD50 of soman and treated with atropine and 2-PAM survived 7 days. The primary histologic lesions in the acute toxicity group were neuronal degeneration/necrosis and spinal cord hemorrhage. The CMPF treated groups (total of 20 animals) had minimal nervous system changes with no significant lesion difference resulting from the different oxime therapies. The primary non-neural lesions were degenerative cardiomyopathy and skeletal muscle degeneration which occasionally progressed to necrosis and mineralization.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholinesterase↗
PubMed1992

Noninvasive detection of heart transplant rejection with positron emission scintigraphy.

Positron emission tomography has recently been used to evaluate ischemic heart disease through changes in myocardial blood flow and carbohydrate metabolism. Positron-emitting tracers were evaluated for their ability to detect acute allograft rejection after heterotopic cardiac transplantation in the rat. Sham-operated controls, nonrejecting isografts, and rejecting allografts were evaluated. Decay-corrected uptake of 13NH3 and 18F 2-fluoro 2-deoxyglucose (FDG) reflects blood flow and glucose flux, respectively. Histologic examination of rejecting allografts documented mild rejection at 4 days and severe acute rejection by 8 days. All isografts were free from rejection. Uptake of FDG is greater in rejecting allografts than in nonrejecting isografts during both severe rejection (2.4% +/- 0.8% versus 0.7% +/- 0.4%; p less than 0.02) and mild rejection (2.1% +/- 0.6% versus 0.4% +/- 0.1%; p less than 0.02). Uptake of NH3 in severely rejected grafts is reduced compared with nonrejecting grafts (0.6% +/- 0.3% versus 1.7% +/- 1.1%; p less than 0.02). There is no difference in NH3 uptake during mild rejection (1.8% +/- 0.7% versus 1.3% +/- 0.3%; p greater than 0.05). Uptake of FDG and NH3 in native hearts of animals from all experimental groups is not significantly different from that in sham-operated controls. Glucose may be a preferred metabolic substrate during rejection. Our data support a humoral mechanism for substrate preference during transplant rejection and a potential diagnostic role for positron emission tomography.

Ammonia↗
PubMed1992

Reduction by pyridostigmine pretreatment of the efficacy of atropine and 2-PAM treatment of sarin and VX poisoning in rodents.

This study concerned the effect of pyridostigmine pretreatment on (a) the antidotal efficacy of atropine and 2-PAM in sarin, tabun, and VX poisoning in mice and guinea pigs and on (b) the oxime-induced reactivation of VX-inhibited whole blood acetylcholinesterase (AChE) of guinea pigs. One hour prior to organophosphate (OP) challenge with sarin, tabun, or VX, animals were given oral doses of pyridostigmine to induce approximately 30 and 60% inhibition of whole blood AChE; controls received vehicle. Mice were challenged im and guinea pigs sc with the OP compounds. Treatment with atropine (11.2 mg/kg to mice; 32 mg/kg to guinea pigs) plus 2-PAM (25 mg/kg) was given im at 10 sec postchallenge in mice and 1 min postchallenge in guinea pigs. In the reactivation experiments, pyridostigmine or saline was given im to guinea pigs 30 min prior to VX (8.24 micrograms/kg, sc), atropine (16 mg/kg) was given im at 1 min, and 2-PAM (25 mg/kg) at 16 min postchallenge. Pyridostigmine significantly enhanced the efficacy of atropine and 2-PAM against tabun in both species. In contrast, pyridostigmine reduced or did not increase the efficacy of atropine and 2-PAM against sarin or VX in both species. Recovery of VX-inhibited AChE by 2-PAM was decreased significantly in pyridostigmine pretreated animals. The results suggest that pyridostigmine pretreatment may adversely effect the efficacy of atropine and 2-PAM as antidotes for VX and sarin intoxication.

Acetylcholinesterase↗
PubMed1992

Staging lung carcinoma with a Tc-99m labeled monoclonal antibody.

Thirty-three patients with biopsy-proven lung cancer and a total of 150 lesions diagnosed by conventional staging procedures were imaged using a Tc-99m labeled monoclonal Fab fragment of an IgG2B murine monoclonal antibody (MoAb) (NR-LU-10, NeoRx Corporation). Immunoscintigraphy demonstrated 100% of primary and 78% of metastatic lesions. MoAb imaging detected 88% of lesions in 12 small cell lung cancer (SCLC) patients and 77% of lesions in 21 non-small cell lung cancer (NSCLC) patients. Based on initial evaluation by other methods, 29 sites of MoAb activity were not associated with evidence of disease. Eleven of these were subsequently shown to represent sites of metastases; 18 remain unconfirmed. Four of ten patients studied with limited NSCLC had eight unsuspected lesions on MoAb imaging. Confirmation of unsuspected lesions in two patients altered initial clinical staging, and surgical therapy was abandoned. This study demonstrates that Tc-99m labeled NR-LU-10 can accurately stage patients with lung cancer.

Carcinoma, Non-Small-Cell Lung↗
PubMed1992

Efficacy of oxime plus atropine treatment against soman poisoning in the atropinesterase-free rabbit.

The oximes pralidoxime chloride (2-PAM), MMB4, and HI-6 were evaluated in combination with atropine as treatments against soman poisoning in atropinesterase-free rabbits. Animals were challenged i.m. with 2 x LD50 soman and treated at the onset of toxic signs with 50 mumols/kg of oxime and 5 or 13 mg/kg atropine. Survival and time to death were compared at 48 hours post-soman challenge. Survival rates in MMB4 and HI-6 treated animals were higher than in 2-PAM-treated animals. The increase in survival was significant at the 13 mg/kg dose of atropine. MMB4 and HI-6 also significantly delayed time to death after soman compared to 2-PAM. The results suggest that MMB4 and HI-6 have potential as useful oximes for treating soman poisoning.

Animals↗
PubMed1992

Twenty years' experience with pulmonary metastasectomy.

From January 1969 through December 1989, 63 patients had 69 operations for pulmonary metastases. Patients ranged in age from 1 to 75 years; there were 36 men and 27 women. Metastasectomy was accomplished through a thoracotomy incision in 59 cases (5 staged, bilateral), and median sternotomy was used in 10 instances. Wedge resection was performed in 54 patients, with segmentectomy in 2, lobectomy in 12, and pneumonectomy in 1. There were no operative deaths. Multiple metastases were present in 29 patients, and a single metastasis in 34. Follow-up ranges from 2 to 204 months (mean = 42 months). Thirty-eight patients remain alive; thirty are free of disease and eight have developed other metastases. Actuarial survival at 5, 10, and 15 years is 40 (CL [confidence limits] 49,31), 36 (CL 44,26), and 24 (CL 35,13) per cent, respectively. Mean actuarial survival is 84 months, and median survival is 58 months. There is no difference in survival whether metastases were single or multiple. Survival is significantly less in groups with primary sarcoma and melanoma (P = .012). While pulmonary metastases may be a manifestation of terminal disease, metastasectomy has an important role in the multidisciplinary management of selected patients when metastatic disease is confined to the lung. Prolonged survival may be achieved in many patients.

Actuarial Analysis↗
PubMed1991

Change in injuries associated with safety belt laws.

Statewide crash data bases from nine states were subjected to time series analyses to detect changes in injuries associated with onset of seat belt laws in the respective states. In each of 18 analyses involving drivers covered by the law observed casualties were below the number forecast on the basis of prior experience and assuming that no law had been enacted. In the case of others, not covered by the law, observed injuries were equally often above or below forecast. Relative to covered drivers not only were the numbers below forecast, but in 12 of the 18 instances there was a statistically significant indication of an abrupt decrease the month the law began.

Accidents, Traffic↗
PubMed1991

The economy as a factor in motor vehicle fatalities, suicides, and homicides.

The effect of the economy as reflected by employment and unemployment rates on motor vehicle fatalities, suicides, and homicides is examined using several national databases. First, regression models are fit to these fatality data-overall as well as for a variety of age-race-gender subgroups. Then time series models-autoregressive integrated moving average (ARIMA) and structural time series analysis-were fit to the data, both with and without the economic indicators, to examine the relative ability of the models to forecast subsequent fatalities. No evidence was found using any of the modeling techniques that knowledge of yearly values of rates of employment, unemployment, and nonlabor force leads to improved forecasts of the level of motor vehicle fatalities, suicides, or homicides in the total U.S. population or within various subpopulations of interest.

Accidents, Traffic↗
PubMed1991

Pharmacokinetics and pharmacodynamics of oximes in unanesthetized pigs.

The pharmacokinetics and cardiovascular pharmacodynamics of two oximes were studied in unanesthetized pigs. Effects of 2-[(hydroxyimino)methyl]-1-methylpyridinium chloride (pralidoxime chloride; 2-PAM Cl; 50 mumol/kg) were compared with those of 1,1-methylene bis[4(hydroxyiminomethyl) pyridinium] dichloride (methoxime; MMB-4; 100 mumol/kg). Cardiopulmonary parameters were monitored and plasma concentrations of oximes were determined from arterial blood samples taken at intervals over a period of 5 hr postinjection. Plasma concentrations for both oximes were fitted to standard pharmacokinetic models using the computer program PCNONLIN. Average pharmacokinetic parameters were determined for each oxime. Only mild to moderate physiological side effects were detected following intramuscular administration. 2-PAM Cl was more rapidly absorbed and distributed in the blood than MMB-4. Although the latter had a slight lag time to attain detectable levels in the blood, retention time was longer than that of 2-PAM Cl.

Acetylcholinesterase↗
PubMed1991

Dose volume histogram analysis of lung radiation from chest wall treatment: comparison of electron arc and tangential photon beam techniques.

The technique of electron arc irradiation of the post-mastectomy chest wall was developed to improve dose uniformity and to reduce lung irradiation in comparison to that seen with standard chest wall tangent photon beam methods. Because of the cephalocaudal variation in chest wall shape and thickness, electron arc treatment planning requires anatomical detail provided by multiple axial CT images of the thorax. To compare the fixed beam and rotational techniques, computer simulated beams covering the chest wall and internal mammary lymphatics were retrospectively applied to the CT-derived contours obtained during treatment planning for 12 consecutive patients receiving adjuvant chest wall treatment by electron arc. The lung dose distribution for each technique was calculated using heterogeneity corrections. The multiplanar 2-dimensional isodose distributions were summed to provide estimated 3-dimensional dose distributions of integral histograms. These reveal that for most of these patients a modest to large improvement in volume-dose relationship occurs with the electron arc technique.

Breast Neoplasms↗
PubMed1991

Management of primary nonrenal parenchymal malignancies with vena caval thrombus.

We report our experience with the management of 7 primary nonrenal parenchymal malignancies with vena caval tumor thrombus. Included are 3 cases of adrenal cortical carcinoma and 1 each of transitional cell carcinoma, embryonal cell testicular carcinoma, pheochromocytoma and primary small cell carcinoma of the lung with metastases to the kidney. Surgical treatment and followup are presented, as well as a review of the literature. An aggressive surgical approach is warranted because prolonged survivals free of disease are possible.

Adrenal Cortex Neoplasms↗
PubMed1991

Operational evaluation of three commercial configurations of atropine/HI-6 wet/dry autoinjectors.

Commercially manufactured wet/dry autoinjectors containing atropine in solution and powdered HI-6 were evaluated using HPLC for consistency of drug delivery with various solvation times and stability of drugs postsolvation at a temperature of 40 degrees C. Three configurations of autoinjector were tested. System A (SYS A), with a specified mixing time of 5 sec, delivered a volume of 3.0 ml containing 1.86 mg of atropine sulfate and 443 mg of the bispyridinium oxime HI-6 dichloride. System B1 (SYS B1) and System B2 (SYS B2), with specified mixing times of 40 sec, delivered volumes of 2.3 ml containing 2.13 and 2.06 mg atropine citrate and 424 and 545 mg HI-6 dichloride, respectively. Average coefficients of variation for SYS A were 3.4% for atropine and 5.8% for HI-6 and for SYS B1 and B2 were 5.2% for atropine and 7.0% for HI-6 determinations. Stored from 3 to 14 days at 40 degrees C after the autoinjector contents were mixed, SYS A delivered 1.77 mg atropine sulfate and SYS B1 and B2 delivered 2.02 mg atropine citrate. The delivery of HI-6 dichloride decreased with a half-life of 34 days for SYS A, 39 days for SYS B1, and 32 days for SYS B2. This resulted in a decrease to 90% of the respective day 0 amount after 4 (SYS A) or 5 (SYS B1 or B2) days.

Atropine↗
PubMed1991

Heart transplantation in children.

Orthotopic cardiac transplantation has been performed in 15 consecutive neonates and children since 1987. Diagnoses include hypoplastic left heart syndrome (5 patients), critical aortic stenosis with small left ventricle (1 patient), complex cyanotic heart disease (6 patients), and cardiomyopathy (3 patients). Twelve patients survived operation and have been followed from 1 to 45 months. Patients less than 6 years of age are managed with cyclosporine +/- azathioprine; in older patients steroid weaning is attempted. Monitoring for rejection is performed with serial echocardiography in patients under 6 years of age; older patients undergo serial biopsies. Actuarial freedom from rejection was 26% 3 months after operation; 47% were free of infection 6 months after operation. There have been no late deaths. Actuarial survival at 3 years is 79%. Nine patients have undergone postoperative catheterization. Resting hemodynamics were normal in every patient. All long-term survivors are asymptomatic and fully active. It is concluded that cardiac transplantation in neonates and children is an effective treatment option for end-stage cardiomyopathy or otherwise incurable congenital heart disease. Long-term survivors have excellent potential for full rehabilitation.

Actuarial Analysis↗
PubMed1991

An unusual appearance of an aneurysmal bone cyst of the thoracic spine.

Aneurysmal bone cysts (ABCs) have been reported in essentially every bone of the human skeleton. This case report documents a very unusual clinical appearance for this entity: a superior mediastinal mass. Also, the patient underwent multiple imaging studies that demonstrated both common (absence of septations) and unusual (extensive involvement of vertebral body with little involvement of posterior elements) characteristics of ABCs.

Adult↗
PubMed1991

Cavoatrial tumor thrombectomy using cardiopulmonary bypass without circulatory arrest.

Of 29 patients with inferior vena caval tumor thrombus, 14 with supradiaphragmatic extension were deemed suitable for operation. Patients (age, 7.5 to 70 years) had renal cell carcinoma (n = 8), Wilms' tumor (n = 2), transitional cell carcinoma (n = 1), and adrenal carcinoma (n = 3). Seven patients had stage III disease, and 7 patients had stage IV disease. Two patients (group A) had unresectable disease at exploratory celiotomy, 4 patients (group B) underwent tumor thrombectomy without cardiopulmonary bypass, and cardiopulmonary bypass was employed in 8 patients (group C). Three of 8 group C patients had Budd-Chiari syndrome at diagnosis. Cardiopulmonary bypass with moderate hypothermia, and inferior vena caval interruption (clip or filter), was employed in all patients. There were no perioperative deaths. Transient neurological impairment was observed postoperatively in 2 patients. Coagulopathy developed in 1 patient who had hepatic encephalopathy and Budd-Chiari syndrome preoperatively and in another patient in whom protamine could not be administered. No patient had acute renal failure requiring hemodialysis. Median survival is 41 and 17 months in groups B and C, respectively. Some authors have advocated profound hypothermia and circulatory arrest in these patients. We find that satisfactory visualization and excision can be performed with cardiopulmonary bypass and moderate hypothermia, avoiding potential renal, hepatic, neurological, and septic complications associated with circulatory arrest.

Adolescent↗
PubMed1990

Evaluating the North Carolina safety belt wearing law.

The North Carolina Seat Belt Law required an evaluation of the effectiveness of the act with a report of the findings to the Legislature three years after the law went into effect. This paper addresses changes in statewide belt usage and in occupant injury associated with that law. Observational data collected bimonthly from a probability sample of 72 sites stratified by geographic region, rural/urban location, road type, and time of day show that belt use rose from a baseline rate of 25% to a warning ticket phase rate of 45%. Belt use then reached 78% upon enforcement and is now nearly 64%. Time series analysis showed that statistically significant reductions in percentages of moderate and serious injuries occurred at the beginning of both the warning ticket and the enforcement phases. Forecasts of injuries and deaths were also developed from the time series models and were compared with observed totals. Warning tickets brought about a modest 5.4% reduction in serious injuries; fatalities among occupants covered by the law showed no change. In contrast, the subsequent enforcement phase saw a reduction of 11.6% in fatalities and 14.6% in serious or worse injuries. This represents an estimated annual savings of 131 lives and over 2,300 serious injuries in North Carolina during the 18 months following onset of enforcement.

Accidents, Traffic↗