Infectious hospital waste disposal a troublesome, costly problem.
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Hospitals↗
Biomedical subjects
S Nelson
Publications and source records attributed to S Nelson.
Expression of alfalfa mosaic virus RNA 4 in transgenic plants confers virus resistance.
Agrobacterium-mediated transfer from a binary vector was used to produce transgenic Nicotiana tabacum plants that expressed coat protein of the plant virus, alfalfa mosaic virus (AMV). Expression levels of the chimeric gene, which was under the control of the cauliflower mosaic virus 19S promoter, were determined in primary transformed plants, in the progeny from self-fertilization and in the progeny from crosses to normal tobacco. RNA transcripts that were of the expected size as well as a protein of the M(r) and antigenicity of AMV coat protein accumulated in the transgenic plants. Plants that expressed the highest levels of coat protein developed fewer primary infections following inoculation with two strains of AMV and developed systemic infection slower than did plants that did not express coat protein. Resistance was specifically against virions of the AMV strains. AMV RNA and the unrelated virus, tobacco mosaic virus, were as infectious on progeny that expressed coat protein as they were on progeny that did not. The relationship between the virus resistance expressed by these transgenic plants and that observed in virus cross-protection is discussed.
Journal Article↗
Decidual luteotropin secretion and action: its role in pregnancy maintenance in the rat.
Studies of rat decidual luteotropin production and action have revealed that decidual mRNA directs the synthesis of a 28,000 MW protein in a cell-free system which binds to prolactin receptors in luteal cells and appears to represent a prohormone for decidual luteotropin. Hybridization studies indicate that although rat decidual and prolactin-like placental hormones bind to prolactin receptors, they possess little homology to other members of the prolactin family. In addition, results of this investigation have revealed a possible physiological relationship between the mesometrial and the antimesometrial cells of the decidual tissue. The large antimesometrial cells produce decidual luteotropin in which secretion and/or synthesis is inhibited by the neighboring mesometrial cells. Since mesometrial cells possess binding sites for decidual luteotropin, it is possible that decidual luteotropin acts on the mesometrial cell to affect the formation of its own inhibitor. Mesometrial cells are rich in glycogen, whose synthesis is stimulated by prolactin-like hormones in other tissues. Therefore, decidual luteotropin may also act on these cells to enhance glycogen formation. In summary, decidual luteotropin appears to have at least two sites of action--the luteal cell, where it can substitute for prolactin in maintaining progesterone production, and the mesometrial cell, where its role remains to be investigated.
Animals↗
Erythromycin-induced suppression of pulmonary antibacterial defenses. A potential mechanism of superinfection in the lung.
Erythromycin is a broad-spectrum antibiotic commonly used in patients with respiratory infections. Certain of these patients become colonized with new microorganisms and develop superinfections. Antibiotics have a number of effects other than simply killing or inhibiting the growth of bacteria and may have direct effects upon host cells, including phagocytes. In vitro and in vivo studies have demonstrated that erythromycin decreases polymorphonuclear leukocyte (PMN) directed migration. To test the hypothesis that erythromycin inhibits normal PMN migration into the alveoli in response to a bacterial challenge, mice were challenged by aerosol inhalation with Proteus mirabilis or Staphylococcus aureus and injected intravenously with erythromycin (50 or 100 mg/kg). Pulmonary bactericidal activity and total lavaged lung cell and differential counts were determined 4 h after bacterial challenge. In control mice, only 24 +/- 2% of the initial inoculum of P. mirabilis was viable at 4 h. At a dose of 100 mg/kg, lung defenses after erythromycin were ablated, allowing the proliferation of P. mirabilis to 113 +/- 5% of the initial inoculum. The number of PMN obtained by lavage after P. mirabilis challenge was also inhibited by erythromycin in a dose-dependent manner. In untreated animals, 5.0 +/- 0.2 x 10(6) PMN were recovered as compared with 3.1 +/- 0.4 x 10(6) and 1.1 +/- 0.3 x 10(6) with increasing doses of erythromycin. Intrapulmonary bactericidal activity against S. aureus was not impaired by erythromycin.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Interactions of clindamycin with antibacterial defenses of the lung.
Clindamycin is speculated to have select advantages in the treatment of certain infections because biologically active antibiotic is internalized by macrophages and PMNs in vitro. By challenging pulmonary host defenses with various bacterial species as probes, we were able to evaluate clindamycin-phagocyte interaction in vivo. A murine model was developed using an implanted mini-osmotic pump to maintain constant clindamycin blood levels at 1/4 MIC (1 microgram/ml). Mice pretreated for 24 h with clindamycin killed a significantly greater percentage of intratracheally inoculated Bacteroides thetaiotaomicron in 4 h than did control animals (37 +/- 2% versus 7 +/- 5%). The enhancing effects of clindamycin on pulmonary defenses could not be duplicated by a 1-h preincubation of B. theta in 1/4 MIC of clindamycin before inoculation into untreated mice. Clindamycin blood levels of 1 microgram/ml did not alter the rate at which Pseudomonas aeruginosa (clindamycin-resistant) was killed by pulmonary defenses, suggesting that clindamycin did not cause nonspecific activation of phagocytic defenses. Both PMNs and alveolar macrophages lavaged from the lungs of clindamycin-treated mice contained bioassayable concentrated intracellular antibiotic. The presence of intracellular antibiotic was further supported by experiments in which the intrapulmonary killing of large numbers of Staphylococcus aureus (sensitive, but not resistant organisms) was significantly enhanced (89 +/- 5 versus 70 +/- 5%) by clindamycin pretreatment. In contrast, phagocytes lavaged from mice with constant 1/4 MIC (4 micrograms/ml) blood levels of penicillin G had no detectable intracellular antibiotic activity and did not augment the intrapulmonary killing of B. theta.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Early experience of health maintenance organizations under Medicare competition demonstrations.
Between 1982 and 1985, health maintenance organizations (HMO's) entered the Medicare market under the Medicare competition demonstrations. The status and experience of these HMO's, their market areas,, and the benefit packages they offered are presented. Information from case studies of 20 of these HMO's is used to discuss the planning process through which the organizations prepared to enter the Medicare market. Data from administrative reports, submitted by the HMO's, are used to describe the operational experience, including enrollments, utilization, and financial performance.
Capitation Fee↗
Antihypertensive, hemodynamic and autonomic profile of a new angiotensin converting enzyme inhibitor, SCH 33844 (spirapril).
SCH 33844 is a new, potent and long-acting inhibitor of angiotensin converting enzyme (ACE). Antihypertensive, hemodynamic and autonomic actions of SCH 33844 were examined in the present series of experiments. Oral administration of 0.3-30 mg/kg reduced blood pressure of spontaneously hypertensive rats. The magnitude of the response was significantly enhanced by pretreatment of the animals with hydrochlorothiazide. Blood pressure remained significantly depressed 24 hr following doses of 3 and 10 mg/kg. Administration of SCH 33844 (3 mg/kg) twice daily to nonpretreated rats or once daily to diuretic-pretreated animals for 5 days resulted in a progressive decrease in blood pressure. The compound did not reduce blood pressure in nephrectomized rats demonstrating the dependence of its action on renal renin. SCH 33844 (1-10 mg/kg orally) also produced dose-related decreases in pressure in diuretic-pretreated conscious normotensive dogs. However, only a small fall in pressure occurred in non-pretreated dogs. Hemodynamic actions were examined in anesthetized dogs. SCH 33844 (1 mg/kg i.v.) reduced blood pressure, increased cardiac output and caused a large fall in peripheral resistance. Autonomic actions were assessed in pithed rats. The compound (10 mg/kg orally) tended to decrease pressor responses to sympathetic activation and to i.v. norepinephrine. This profile is probably due, at least in part, to vasorelaxation following suppression of angiotensin II generation. In conclusion, SCH 33844 is a potent, long-lasting antihypertensive agent which reduces peripheral vascular resistance and possesses only slight autonomic effects.
Adrenergic Agonists↗
Narcolepsy. Diagnosis, treatment, and management.
Narcolepsy is a syndrome of unknown origin characterized by the irresistible urge to sleep. Other important features are disturbed nocturnal sleep and abnormal manifestations of REM sleep such as cataplexy, sleep paralysis, and abnormal sleep-onset REM periods. Narcolepsy is not a rare condition. With a prevalence between 2 and 10 per 10,000 individuals, it is about as common as multiple sclerosis. Like multiple sclerosis, narcolepsy can be disabling and have profound consequences for job capability, public safety, sense of self-worth, and social image.
Animals↗
A prospective comparison of selective and universal electronic fetal monitoring in 34,995 pregnancies.
We investigated the effects of using intrapartum electronic fetal monitoring in all pregnancies, as compared with using it only in cases in which the fetus is judged to be at high risk. Predominant risk factors included oxytocin stimulation of labor, dysfunctional labor, abnormal fetal heart rate, or meconium-stained amniotic fluid. This prospective alternate-month clinical trial took place over a 36-month period during which 34,995 women gave birth. In alternate months, either 7 (for "selective monitoring") or 19 (for "universal monitoring") fetal monitors were made available in the labor and delivery unit. During the "selective" months, 6420 of 17,409 women (37 percent) were electronically monitored, as compared with 13,956 of 17,586 women (79 percent) during the "universal months." Universal monitoring was associated with a small but significant increase in the incidence of delivery by cesarean section because of fetal distress, but perinatal outcomes as assessed by intrapartum stillbirths, low Apgar scores, a need for assisted ventilation of the newborn, admission to the intensive care nursery, or neonatal seizures were not significantly different. We conclude that not all pregnancies, and particularly not those considered at low risk of perinatal complications, need continuous electronic fetal monitoring during labor.
Adult↗
In vitro effect of acidulated phosphate fluoride gel on the surface of composites with different filler particles.
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Acidulated Phosphate Fluoride↗
Impairment of antibacterial defense mechanisms of the lung by extrapulmonary infection.
To determine whether extrapulmonary infection alters antibacterial defenses of the lung, we challenged mice with peritonitis due to Escherichia coli by aerosol inhalation with either Staphylococus aureus or Pseudomonas aeruginosa. In animals without peritonitis, 14% +/- 5% and 11% +/- 1% of the initially deposited viable S. aureus and P. aeruginosa, respectively, remained in the lungs at 4 hr. In contrast, in mice with peritonitis, at 4 hr 45% +/- 9% of the staphylococci were recoved, and the P. aeruginosa had increased to 948% +/- 354% of the initial inoculum. Proliferation of P. aeruginosa in mice with peritonitis was associated with impaired recruitment of polymorphonuclear neutrophils (PMNs) into the lungs. In contrast, a noninfectious stimulus induced more PMNs into the peritoneal cavity than did intraabdominal sepsis but only minimally impaired PMN recruitment into the lungs after aerosol challenge with P. aeruginosa. Sterile intraperitoneal stimulation did not significantly impair intrapulmonary killing of P. aeruginosa. Levels of antigenic C3 and functionally active C5 were significantly depleted in mice with peritonitis due to E. coli. We conclude that the systemic effects of sepsis, including complement depletion, contribute to the decreased pulmonary PMN recruitment and to impaired intrapulmonary bacterial killing of animals with peritonitis due to E. coli.
Animals↗
Characterization of the pulmonary inflammatory response to an anaerobic bacterial challenge.
Anaerobic bacteria from the oral flora are important causes of aspiration pneumonia and lung abscess. However, the pulmonary antibacterial response to these organisms has not been well described. To define this, mice were intratracheally inoculated with 10(9) Bacteroides gingivalis, a member of the B. melaninogenicus group, and a common clinical isolate from periodontal disease and anaerobic pulmonary infections. Studies after intratracheal challenge included bacteriologic and histopathologic examination, pulmonary cellular response, lactic dehydrogenase (LDH) and albumin levels in lung lavage fluid, and wet lung weight. Overall mortality was 25%. In the surviving animals, pulmonary lavage showed a marked recruitment of polymorphonuclear leukocytes that was associated with significant bacterial killing by 48 h. Histopathologic examination showed an acute, severe necrotizing bronchopneumonia. Pulmonary abscess formation occurred in 37% of animals. Severe parenchymal damage was further documented by a marked increase in LDH levels in lavage fluids. Mean LDH levels in lavage fluid increased to 850 +/- 25 units/first lavage at 24 h postchallenge compared with control values of 65 +/- 10 units/first lavage. Lung lavage also demonstrated an extensive influx of serum albumin consistent with injury to the alveolar capillary membrane. Albumin levels in lung lavage were highest at 24 h after intratracheal challenge (3.25 +/- 0.3 mg/first lavage), whereas lavage fluid from control mice had nondetectable albumin levels. Wet lung weights maximally increased from 0.12 +/- 0.01 g in control mice to 0.28 +/- 0.03 g 24 h after bacterial-challenge. These data demonstrate tht B. gingivalis causes marked inflammation in the lung that progresses to severe bronchopneumonia and lung abscess.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
The toxicity of acetaminophen and N-acetyl-p-benzoquinone imine in isolated hepatocytes is associated with thiol depletion and increased cytosolic Ca2+.
The effects of acetaminophen and its major toxic metabolite, N-acetyl-p-benzoquinone imine (NAPQI), have been investigated in hepatocytes isolated from 3-methylcholanthrene-pretreated and -untreated rats, respectively. The two compounds produced qualitatively similar changes although the quinone imine was toxic with shorter incubations periods and at lower doses. Both agents caused an elevation of cytosolic Ca2+, assessed by phosphorylase a activity, which was accompanied by the concomitant appearance of plasma membrane blebs. A loss of mitochondrial Ca2+ was also observed. This disruption of Ca2+ homeostasis always preceded cell death. Studies with NAPQI showed that low doses were able to cause complete Ca2+ release from isolated liver mitochondria which was accompanied by pyridine nucleotide oxidation and preceded membrane damage. NAPQI also produced a rapid, dose-dependent depletion of both cytosolic and mitochondrial reduced glutathione as well as a loss of protein-bound SH groups. This loss of protein thiols may have been responsible for the observed inhibition of the high-affinity Ca2+-ATPase activity of the plasma membrane fraction isolated from NAPQI-treated cells. In addition, NAPQI inhibited microsomal Ca2+ uptake which would further contribute to the elevation in cytosolic Ca2+. Our results suggest that acetaminophen and N-acetyl-p-benzoquinone imine exert their cytotoxic effects via a disruption of Ca2+ homeostasis secondary to the depletion of soluble and protein-bound thiols. This mechanism may prove to be of general applicability to a variety of hepatotoxins.
Acetaminophen↗
Methylprednisolone impairs the bactericidal activity of alveolar macrophages.
Corticosteroid treatment of patients following acid aspiration has been reported to increase the incidence of bacterial pneumonia, with Staphylococcus aureus being a common isolate. We hypothesized that administration of methylprednisolone (MP) to mice with acid-injured lungs would impair pulmonary clearance of S. aureus by compromising the bactericidal oxidative metabolism of pulmonary phagocytes. Using an inhalational bacterial challenge, we established that MP decreased pulmonary clearance of S. aureus. In mice with normal lungs and without MP treatment 14 +/- 2% of all initially deposited Staphylococci remained at 4 hr compared to 28 +/- 2% remaining in the lungs of mice with MP treatment. In mice with acid-injured lungs, MP caused a greater impairment of S. aureus clearance at 4 hr with 44 +/- 10% of all initially deposited bacteria remaining in the lungs of control mice and 210 +/- 24% remaining in the lungs of MP-treated mice. After it was demonstrated that there was no difference in the numbers of phagocytic cells obtained by lung lavage from mice with or without MP treatment, the bactericidal oxidative metabolism of these cells was quantitated using luminol-amplified chemiluminescence. Phagocytic cells from mice not exposed to S. aureus displayed minimal chemiluminescence whether they were treated with saline (22 +/- 14 mV) or MP (14 +/- 8 mV). In contrast, phagocytes from saline-treated mice exposed to S. aureus showed a significant increase in chemiluminescence (159 +/- 22 mV). Pretreatment with MP, however, prevented this response to S. aureus (21 +/- 13 mV), indicating that bactericidal oxidative metabolism of these phagocytic cells had been suppressed.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Characteristics of rural communities and the changing geographic distribution of physicians.
This research paper presents the results of a comparison of the characteristics of rural counties which attracted and failed to attract young physicians during the past decade. The data utilized in this research were from the Area Resource File which contains data on physicians for 1975 and 1979 and which permitted the examination of flows of physicians in counties over this period. Characteristics of rural counties examined included demographic and economic characteristics, population density, physical characteristics, health status measures, and the availability of health resources. Results from this preliminary analysis indicate that counties with at least 25,000 population were more likely to have gained a young physician and that, of all counties which added young physicians, the majority gained only one or two. Characteristics which best distinguished counties gained or lost physicians included population and population growth rate, health resources, growth rate of per capita income, and the proportion of the population agriculture.
Catchment Area, Health↗
Aminophylline-induced suppression of pulmonary antibacterial defenses.
Respiratory infections are frequently observed in patients with chronic obstructive pulmonary disease, indicating that host defenses are compromised. Antibacterial defenses of the lung against such infections include the alveolar macrophage and polymorphonuclear leukocytes (PMN) that migrate into the lung to provide auxiliary phagocytic defenses. To test the hypothesis that aminophylline acutely impairs pulmonary antibacterial defenses, mice were challenged by aerosol inhalation with Staphylococcus aureus or Proteus mirabilis and injected intraperitoneally with aminophylline (20, 40, or 80 mg/kg). Pulmonary bactericidal activity and total lavaged lung cell and differential counts were determined 4 h after bacterial challenge. The highest dose of aminophylline suppressed the killing of S. aureus so that 55 +/- 5% of the initial viable bacteria remained as compared with 22 +/- 4% in the control animals. In contrast, there was a dose-related suppression of pulmonary antibacterial defenses against gram-negative bacteria. With doses of 40 and 80 mg/kg, lung defenses were ablated, allowing the proliferation of P. mirabilis to 115 +/- 9% and 253 +/- 9%, respectively, the control value being 26 +/- 3%. The number of PMN obtained by lavage after aerosol challenge with P. mirabilis was also inhibited by aminophylline in a dose-dependent manner. From the lungs of untreated animals 5.0 +/- 0.3 X 10(6) PMN were recovered as compared with 3.3 +/- 0.1 X 10(6), 2.5 +/- 0.2 X 10(6), and 1.8 +/- 0.1 X 10(6), respectively, with increasing doses of aminophylline. The bactericidal activity of lavaged PMN from the lungs of aminophylline-treated rats challenged with the gram-negative bacterium in vivo was significantly depressed when compared with that in control animals.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Dialysis osteomalacia: a possible role for zirconium as well as aluminium.
Six patients with dialysis osteomalacia were studied before and after treatment with desferrioxamine. Before treatment, all six had severe osteomalacia with histochemical evidence of metals at the mineralization front, confirmed by energy dispersive X-ray microanalysis to include Al, Zr and Fe. Zr was not detected by histological staining in patients without dialysis osteomalacia. After treatment a decrease of Al and Zr was associated with improvement in clinical, biochemical, radiological and histological parameters. These observations suggest the possibility of a role for metals other than Al in the pathogenesis of dialysis osteomalacia.
Chronic Kidney Disease-Mineral and Bone Disorder↗
A 40-year-old man with chills, fever, weight loss, and a productive cough.
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Acquired Immunodeficiency Syndrome↗