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Biomedical subjects

R C Reynolds

Publications and source records attributed to R C Reynolds.

At least 55 records · Page 3Linked to original sources
PubMed1989

Factors affecting survival in allogeneic bone marrow transplantation.

From 1979 to 1988, 82 allogeneic and 2 syngeneic bone marrow transplants (BMT) were performed in 78 patients (age range 13-49 years) with the following diagnoses: acute myelogenous leukemia (AML) (21 patients); acute lymphoblastic leukemia (ALL) (15 patients); chronic myelocytic leukemia in chronic, accelerated, or blastic phase (CML-CP, AP or BC) (25 patients); myelodysplastic syndrome (MDS) (1 patient); multiple myeloma (MM) (1 patient); Hodgkin's disease (HD) (1 patient); diffuse poorly differentiated lymphoma (DPDL) (1 patient); aplastic anemia (AA) (13 patients). Univariant analyses were carried out to determine factors of importance in predicting outcome. AML patients receiving transplants in remission had 12/19 (63%) survivors. Only one of seven ALL patients receiving transplants in remission survives free of disease, and none of eight patients receiving transplants in relapse survived. Six ALL patients relapsed. In CML, 6 of 16 (40%) patients receiving transplants in CP survive; two of nine patients (22%) in AP or BC survive. Of the 13 aplastic anemias, 8 (62%) survive. Graft-vs.-host disease (GVHD) was evaluated in 75 patients, 24 of 33 (73%) who developed GVHD died, compared to 24 of 44 (55%) who did not develop GVHD. Of the 30 patients given the combination of methotrexate (MTX) plus cyclosporine (CSP), only 23% developed GVHD, compared to 58% of those not given the combination. Interstitial pneumonia (IP) occurred in 16 patients and was fatal in 15. The introduction of daily acyclovir and weekly intravenous gamma globulin in 1985 was associated with little reduction in the frequency of IP (from 20% to 18%). However, survival increased from 21% to 47%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1988

Pneumococcal aortitis with rupture of the aorta. Report of a case and review of the literature.

Microbial arteritis, an entity often considered under the category of mycotic aneurysms, is an uncommon infectious process which generally results from bacteremic seeding of a preexisting aortic lesion. This report describes a fatal case of microbial arteritis involving a 51-year-old man who presented as an outpatient with diffuse myalgias and abdominal pain of approximately two weeks' duration. Necropsy finding revealed an exsanguinating hemorrhage from an infected nonaneurysmal abdominal aortic plaque caused by Streptococcus pneumoniae. Documented cases of microbial aortitis due to S. pneumoniae are quite rare in present times and were not often observed in the preantibiotic era even in the setting of bacterial endocarditis. The pathology, pathogenesis, and incidence of aneurysmal and nonaneurysmal aortic infections, with special reference to the pneumococcus, are reviewed.

Aneurysm, Infected↗
PubMed1988

Evaluation of developmental toxicity data: a discussion of some pertinent factors and a proposal.

There is currently no well-accepted standard method for evaluation of developmental toxicity data. This paper presents one approach to the evaluation of developmental toxicity data. We initially identify some pertinent factors that influence the interpretation of animal data and summarize the literature pertaining to these factors. Such factors include the quality and quantity of data and the relationship between maternal and developmental toxicity. We proceed with a discussion of quantitative assessment of data and propose schemes for qualitative and quantitative developmental hazard assessments.

Animals↗
PubMed1988

Pulmonary hypertension and pulmonary vascular reactivity in beagles at high altitude.

It is unclear whether dogs develop pulmonary hypertension (PH) at high altitude. Beagles from sea level were exposed to an altitude of 3,100 m (PB 525 Torr) for 12-19 mo and compared with age-matched controls remaining at low altitude of 130 m (PB 750 Torr). In beagles taken to high altitude as adults, pulmonary arterial pressures (PAP) at 3,100 m were 21.6 +/- 2.6 vs. 13.2 +/- 1.2 Torr in controls. Likewise, in beagles taken to 3,100 m as puppies 2.5 mo old, PAP was 23.2 +/- 2.1 vs. 13.8 +/- 0.4 Torr in controls. This PH reflected a doubling of pulmonary vascular resistance and showed no progression with time at altitude. Pulmonary vascular reactivity to acute hypoxia was also enhanced at 3,100 m. Inhibition of prostaglandin synthesis did not attenuate the PH or the enhanced reactivity. Once established, the PH was only partially reversed by acute relief of chronic hypoxia, but reversal was virtually complete after return to low altitude. Hence, beagles do develop PH at 3,100 m of a severity comparable to that observed in humans at the same or even higher altitudes.

Altitude↗
PubMed1987

Carbon tetrachloride-induced morphologic alterations in isolated rat hepatocytes.

Isolated rat hepatocytes were exposed to CCl4 in doses commonly used in in vitro studies and for which we have provided biochemical evidence would induce solvent injury. Rapidly evolving morphologic alterations were observed in the plasma membrane, endoplasmic reticulum, and mitochondria. Swelling and fusion of surface microvilli with formation of blebs were particularly prominent and occurred within 2 min of exposure. Blebs regressed in some hepatocytes without evidence of cell death, when these cells were exposed to CCl4 under conditions promoting its evaporation. Disorganization of endoplasmic reticulum and mitochondrial injury were also prominent early findings. Rapid appearance of diffuse ultrastructural alterations in isolated hepatocytes exposed to CCl4 is consistent with nonspecific membrane injury induced by solvent effects.

Animals↗
PubMed1987

Pulmonary edema in dogs fails to cause reflex responses.

Pulmonary edema has been proposed as a stimulus for pulmonary C-fibers. Stimulation of pulmonary C-fibers causes depression of cardiovascular function and either tachypnea or apnea. Our objective was to determine whether pulmonary edema, induced by either increasing pulmonary vascular permeability with alloxan or hydrostatic challenges, would elicit depression of cardiovascular function or changes in frequency of inspiratory activity. Utilizing a preparation in which the left pulmonary vessels and left airway were isolated, we monitored systemic blood pressure (BP), heart rate (HR), and diaphragm contractions (DC) in 13 anesthetized dogs. Injection of alloxan into the left pulmonary artery (LPA) produced transient decreases in HR, BP, and frequency of DC within 20 s of injection with no subsequent cardiorespiratory changes up to 5 min. These alloxan injections also caused coagulation necrosis. Generation of hydrostatic pulmonary edema in the left lung caused no changes in HR, BP, or in the frequency and amplitude of DC. We conclude that alloxan does stimulate reflex cardiorespiratory depression consistent with C-fiber stimulation, but these reflex responses are probably caused by alloxan's caustic effect and not by the resultant edema. We also conclude that pulmonary edema induced by increased hydrostatic pressure does not evoke any reflex cardiovascular responses or changes in frequency of inspiratory activity.

Alloxan↗
PubMed1987

Reflex cardiorespiratory responses to pulmonary vascular congestion.

The purpose of these studies was to determine the reflex responses of the cardiovascular system and central inspiratory activity caused by pulmonary vascular congestion. We used a canine preparation in which the left lung was isolated in situ and could be exposed to a variety of stimuli, including distension of the pulmonary capillaries with blood, without direct mechanical or chemical alterations on the circulation. We found that lung expansion to 30 cmH2O and stimulation of nerve endings of the left lung with capsaicin caused pronounced transient reflex bradycardia (-30 to -50 beats/min) and hypotension (-25 to -40 mmHg) and caused reflex cessation of inspiratory activity. Pressurizing the left pulmonary vessels by injecting blood in volumes sufficient to raise pulmonary transcapillary pressures to 30 mmHg caused no changes in heart rate, systemic arterial pressure, or inspiratory muscle activity. These results lead us to conclude that pulmonary vascular congestion does not stimulate pulmonary C-fibers or any other nerve endings to such a degree as to cause detectable changes in blood pressure, heart rate, or central inspiratory activity. Morphometric analysis revealed distended capillaries engorged with blood, but the alveolar wall surface area was not increased which raises the possibility that expansion of the alveolar membrane may be needed to mechanically initiate the C-fiber reflex.

Animals↗
PubMed1985

The interaction of androgen and thyroid hormones in the submandibular gland of the genetically hypothyroid (hyt/hyt) mouse.

The development and maintenance of granular convoluted tubule cells in the mouse submandibular gland (SMG) and the production of renin-1, renin-2, and epidermal growth factor (EGF) by these cells are under complex hormonal control. Hypophysectomy causes profound involution and loss of renin activity in this gland. We have shown previously that T4 acts synergistically with 5 alpha-dihydrotestosterone (DHT) to restore SMG morphology and renin-2 activity in hypophysectomized female mice. Investigating the mechanism of T4 and DHT interaction in the hypophysectomized mouse proved impractical, and in the present study we have used genetically hypothyroid (hyt/hyt) mice that carry the structural gene for renin-1 but not for renin-2. Levels of SMG renin-1 and EGF in hyt/hyt mice were less than 4% of those in euthyroid (hyt/+) littermates. Administration of a pharmacological dose of T4 (2.5 micrograms/g BW X day, ip) to male hyt/hyt mice for 18 days restored SMG renin-1 and EGF to near-normal levels. The weights of SMG, seminal vesicle, and epididymis were also lower in hypothyroid mice and increased in response to T4. The effect on SMG renin-1 and EGF of either DHT (150 micrograms/g BW every other day, sc) or T4 (0.025-2.5 micrograms/g BW.day, ip) was blunted in female hyt/hyt mice. A combination of DHT and T4 (0.1 microgram/g BW.day) that restored total circulating T4 and T3 to physiological levels acted synergistically to increase SMG renin-1 and EGF. The administration of 2.5 micrograms T4/g BW.day plus DHT for 7 days increased the specific activity of SMG renin-1 and EGF to levels approaching those in euthyroid littermates given the same treatment. T4 (0.1 microgram/g BW.day) did not alter the quantity or sedimentation characteristics of high affinity androgen-binding protein in SMG from female hyt/hyt mice and induced SMG renin-1 in Tfm/Y mice. Thus, T4 does not appear to exert its effect via the androgen receptor. The administration of DHT and T4 to female hyt/hyt mice produced lower circulating levels of both T3 and T4 than the same dose of T4 given alone, suggesting that DHT does not act by enhancing the conversion of T4 to T3. This study demonstrates that the interaction of T4 and DHT is not a pharmacological phenomenon, but occurs at doses of T4 that restore serum T3 and T4 in female hyt/hyt mice to normal or near-normal levels.(ABSTRACT TRUNCATED AT 400 WORDS)

Androgens↗
PubMed1985

Alterations of ultrastructure and elemental composition in cultured neonatal rat cardiac myocytes after metabolic inhibition with iodoacetic acid.

The purpose of this study was to document changes in cellular fine structure and elemental composition, and their relationship to progression of cell injury, in cultured neonatal rat cardiac myocytes in which impaired energy metabolism was produced by the metabolic inhibitor, iodoacetic acid (IAA). In order to quantitate changes in the concentrations of elements and their subcellular distribution in individual myocytes, electron probe x-ray microanalysis was performed on freeze-dried cryosections of rapidly frozen cells. After 1 hour of exposure to IAA, ATP level was not significantly reduced. Most cells exhibited minimal ultrastructural alterations and had normal elemental profiles, whereas some cells (10 to 25%) had increased sodium and calcium in mitochondria and cytoplasm. After exposure to IAA for 1.5, 2, or 4 hours, the ATP level was reduced to below one third of control, and remained decreased 24 hours after removal of IAA, indicating irreversible depression of this variable. After exposure to IAA for 1.5 hours no longer, many cells showed severe ultrastructural alterations, including contraction or swelling of mitochondria and distortion of the cristae, myofibrillar hypercontraction, and formation of fluid-filled blebs. At 1.5 and 2 hours, approximately 75% or more of the myocytes had increased sodium and calcium and decreased potassium and magnesium in mitochondria, nuclei, and cytoplasm. Thus, the development of an increased calcium concentration in cytoplasm as well as mitochondria of most myocytes was a feature of this transitional period. These data indicate that progressive alterations in the levels and distribution of elements accompany the development of severe ultrastructural changes and irreversible injury in response to impaired energy metabolism in cultured myocytes. These elemental alterations include accumulation of calcium in cytoplasm and mitochondria of myocytes in this model.

Adenosine Triphosphate↗
PubMed1984

Metabolic fate and disposition of [14C]hydroquinone given orally to Sprague-Dawley rats.

Hydroquinone (HQ) is used widely in industry and in commerce and is considered to have a low degree of toxicity. Although the metabolism of HQ has been studied elsewhere, a complete materials balance has not been reported. We investigated the metabolism of HQ in naive and HQ pretreated male Sprague-Dawley rats. [14C]HQ was administered by gavage in single doses of 5, 30, or 200 mg/kg to naive rats. HQ was given repeatedly by gavage to male rats at 200 mg/kg for 4 consecutive days followed by a single dose with 200 mg/kg of [14C]HQ. In separate studies rats were fed 5.6% unlabeled HQ in the diet for 2 days or were dosed by gavage with 311 mg/kg [14C]HQ. The excretion patterns of [14C]HQ and its metabolites were similar for rats dosed singly or repeatedly. Rats given a single dose of 200 mg/kg of [14C]HQ excreted 91.9% of the dose in the urine within 2-4 days; 3.8% was excreted in the feces, about 0.4% was excreted in expired air, and 1.2% remained in the carcass. Radioactivity was widely distributed throughout the tissues with higher concentrations in the liver and kidneys. A decrease in 14C tissue concentrations occurred from 48 to 96 h. The only radiolabeled compounds in the urine were HQ (1.1-8.6% of the dose), hydroquinone monosulfate (25-42%), and hydroquinone monoglucuronide (56-66%). Similar findings were observed for rats given HQ in the feed. There were no significant increases from controls for absolute or relative liver weights, liver microsomal protein concentrations, cytochrome b-5, cytochrome P-450 or cytochrome c reductase activity in rats dosed repeatedly with 200 mg/kg HQ. Cytochrome P-450 values were slightly but significantly decreased in rats dosed repeatedly with HQ compared with controls.

Administration, Oral↗
PubMed1984

Some effects of trichloroethylene on mouse lungs and livers.

Repeated administration of trichloroethylene (TCE) to mice by either i.p. injection or by inhalation increased the activity of hepatic microsomal NADPH cytochrome-c reductase. The NADPH cytochrome c reductase activity in microsomes isolated from lungs of animals treated with TCE by inhalation was decreased relative to controls (untreated animals). TCE inhalation was associated with pathologic changes in lungs, but not in livers of the treated animals. The duration of exposure is probably an important factor however, since animals exposed for only 1 hr per day exhibited neither pathologic changes in the lungs nor an alteration of enzyme activity. These findings indicate that inhalation of TCE, without prior treatment with inducers, can enhance activity of the hepatic mixed function oxidase system. The reduced activity of the pulmonary mixed function oxidase system in animals that inhaled TCE may reflect injury to the lungs.

Animals↗
PubMed1984

Comparative analysis of drug distribution costs for controlled versus noncontrolled oral analgesics.

Total costs for controlled substance oral analgesics and non-controlled analgesics were compared for patients at a 548-bed university hospital. During 1983, all cost elements involved in drug delivery (excluding large-volume parenterals) were identified. Direct and indirect pharmacy labor costs were determined. Personnel costs were calculated from time studies of nurses (in 1979-80) and pharmacy technicians (in 1982). Other pharmacy costs, based on the hospital's 1982 data, included inventory holding costs, computer services, supplies, and drug acquisition costs. Costs were calculated for four oral analgesics--acetaminophen with codeine, aspirin with codeine, ibuprofen, and zomepirac sodium--used during a 30-day period in 1981. For all medications, total average cost per dose for 1,949,418 doses was $2.44, of which 41% was drug acquisition cost. Personnel costs for pharmacy and nursing accounted for 43% and 11%, respectively, of total costs. For 46% of 5111 oral analgesic doses, frequency of administration was at least four times daily. Average purchase cost per dose for the oral analgesics was $0.15, while total costs for the controlled and non-controlled drugs were $1.02 and $0.50, respectively. For the four oral analgesics in this study, cost was affected by dosage schedule and controlled or noncontrolled status. Calculation of the total average cost per dose is useful in projecting annual costs and in identifying areas for cost reduction.

Administration, Oral↗