Coralyne. Intercalation with DNA as a possible mechanism of antileukemic action.
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Biomedical subjects
Publications and source records attributed to J J Doyle.
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Direct and indirect immunofluorescence techniques were used to study the effects of host antibodies on surface membrane antigens of viable Leishmania parasites in vitro. Antisera to L. enriettii and L. tropica caused surface membrane antigens of these parasites to aggregate, move toward the poles of the parasite, and to eventually disappear. This sequence did not occur at low temperature or in the presence of some metabolic inhibitors. Antigen subsequently reappeared on the parasite membrane. These phenomena appear to be similar to those described in mammalian cells. Antibodies may therefore effect an alteration in the surface membrane structure of living protozoan parasites.
Diets containing 0, 5, 15, 30, and 60 ppm of cadmium were fed to male lambs for 191 days to ascertain what effect cadmium might have on the tissue concentrations of copper, zinc, iron, and manganese. The cadmium content of all tissues increased with an increase in dietary cadmium. The iron concentration of the ileum tissue was significantly depressed in the cadmium-treated groups compared with that of the controls. Liver copper, iron, and manganese were significantly depressed and liver zinc significantly increased by varying levels of dietary cadmium. The copper concentrations of the spleen and testicles were significantly decreased by all levels of cadmium while the copper and zinc concentrations of the kidneys were significantly increased in the 30 and 60 mug Cd/g and 15, 30, and 60 mug Cd/g groups, respectively. In general, cadmium had no significant effect on the rumen, abomasal, heart, or lung concentrations of copper, zinc, iron, or manganese.
Six species of microorganisms, Escherichia coli, Bacillus cereus, Lactobacillus acidophilus, Staphylococcus aureus, Streptococcus faecalis and Actinomyces niger, were grown under suitable conditions in appropriate media. Cadmium chloride was added to provide 0, 5, 10, 20, 40, and 80 mug of Cd per ml. At 40 and 80 mug of Cd per ml, E. coli and B. cereus grew well and the other species were repressed. Cd uptake patterns differed significantly among the species tested. The significance of these data with respect to Cd in food chains is discussed.
The effects of 5 pg Cd per millilter of drinking water on body weight gain, food intake, systolic blood pressure, '24Na, '42K; and water retention and freference for NaCl solution in male and female rats were studied. After 205 days, Cd had no significant effect on weight gain, food intake, water intake, or feed efficiency. The'24Na retention of the Cd-fed male and female rats was greater at 161 days than in the control animals and was significantly greater (P less than 0.05) in the Cd-treated females than in the control females at 294 days. In vivo retention of '42K was significantly greater in the Cd-treated males than in the control males at 189 days, butthe oppisite was true of the Cd-treated females in comparison with female control animals. There were no significant differences between treatments in '42K retention after 330 days. No significant differences were found between treatments in systolic blood pressure. Water retention was significantly greater in the Cd-treated males and females than in the control animals after 320 days. Preference for 0.20 M NaCl was significantly greater in the Cd-fed males than in the control males at 277 days. Possible mechanisms which might explain the sodium retention in thhe Cd-fed rat are discussed.
Incubation in vitro of viable Leishmania enriettii with antibodies from infected or immune guinea pigs and a fluorescein-labeled antiguinea pig Ig conjugate induced aggregation of surface antigens to form a "cap" over the anterior pole of the amastigote and over both the anterior and posterior poles of the promastigote form of the parasite. Cap formation occurred only with optimum quantities of guinea pig antibodies and was inhibited by low temperature and the metabolic inhibitors, sodium azide and iodoacetamide. The aggregated antigens were rapidly lost from the surface of the parasite but reappeared after 3 h of incubation at 23 degrees C. This phenomenon of ligand-induced membrane antigen movement is apparently similar to that described in mammalian cells, and may represent the first stage of the interaction between host antibodies and the surface membrane of protozoal parasites.
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The cost of induction and maintenance of anesthesia is analyzed in this article from the perspective of a health maintenance organization's (HMO) chief financial officer. While earlier economic studies tended to focus on the raw cost of anesthesia drugs, our model also includes the cost of the clinical labor involved in administering the drug as well as the fixed costs associated with the facility. Such a model is consistent with the goal of an HMO, which is to provide high-quality health care services to its membership while containing costs. Our model disaggregated the costs associated with anesthesia into cost centers. The costs associated with two anesthesia regimens, propofol and thiopental/isoflurane, were calculated and analyzed via cost-minimization methods. Our data were acquired from a prospective economic trial conducted in university, community, and HMO hospitals. Because institutional pricing policies differ greatly, only the findings at the HMO hospital are presented in this report. Our results suggest that intra-abdominal surgical procedures with a duration of less than 4 hours that use propofol for induction and maintenance of anesthesia reduce the total cost of surgery by $202.71, compared with the costs of using thiopental/isoflurane. Sensitivity analysis maintains the robustness of the conclusions with regard to all major parameters.
OBJECTIVE: To determine the most cost-effective oral therapy for the treatment of Major Depressive Disorder (MDD) in Italy. METHOD: We conducted a pharmacoeconomic evaluation based on a decision analytic model that examined the treatment of major depressive disorder (MDD) in Italy. The analysis compared the serotonin norepinephrine reuptake inhibitor (SNRI), venlafaxine extended-release (venlafaxine XR), to selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs). A meta-analysis was performed to determine the clinical rates of success. The meta-analytic rates were applied to the decision analytic model to calculate the expected cost and expected outcomes for each anti-depressant comparator. Cost-effectiveness was determined using the expected values for both a successful outcome, and a composite measure of outcome termed 'symptom-free days'. A policy analysis was conducted to estimate the financial impact to the Servizio Sanitario Nazionale (SSN). RESULTS: Treatment of MDD with venlafaxine XR yielded the highest overall efficacy rates for outpatients (73.7%) versus SSRIs (61.4%) and TCAs (59.3%), and inpatients (62.3%) versus SSRIs (58.6%) and TCAs (58.2%). Venlafaxine XR had the lowest dropout rates due to lack of efficacy (4.8%) versus SSRIs (8.4%) and TCAs (6.8%), and adverse drug reactions (10.9%) versus SSRIs (17.4%) and TCAs (23.1%). Initiating treatment of MDD with venlafaxine XR yielded the lowest expected cost for outpatients and for inpatients. The total resulting savings for the SSN at a 5% venlafaxine XR utilization was estimated between L 963 million and L 3,210 million. CONCLUSION: This study confirms that venlafaxine XR is generally a cost-effective treatment of MDD. Additionally, the results of this investigation suggest that increased utilization of venlafaxine XR will favorably impact the SSN.
METHODS: We conducted a multinational pharmacoeconomic evaluation comparing the immediate release form of a new class of serotonin norepinephrine reuptake inhibitor (SNRI), venlafaxine IR to the selective serotonin reuptake inhibitors (SSRIs) and the tricyclic antidepressants (TCAs) in the treatment of acute major depressive disorder (MDD) in 10 countries (Germany, Italy, Netherlands, Poland, Spain, Sweden, Switzerland, United Kingdom, United States, and Venezuela). We designed a decision analytic model assessing the acute phase of MDD treatment within a 6-month time horizon. Six decision tree models were customized with country-specific estimates from a clinical management analysis, meta-analytic rates from two published meta-analyses, and a resource valuation of treatment costs representing the inpatient and outpatient settings within each country. The meta-analyses provided the clinical rates of success defined as a 50% reduction in depression scores on the Hamilton Depression Scale (HAM-D) or the Montgomery-Asberg Depression Rating Scale (MADRS). Treatment regimen costs were determined from standard lists, fee schedules, and communication with local health economists in each country. The meta-analytic rates were applied to the decision analytic model to calculate the expected cost and expected outcomes for each antidepressant comparator. Cost-effectiveness was determined using the expected values for both a successful outcome, and a composite measure of outcome termed symptom-free days. A policy analysis was conducted to examine the health system budget impact in each country of increasing the utilization of the most effective antidepressant found in our study. RESULTS: Initiating treatment of MDD with venlafaxine IR yielded a lower expected cost compared to the SSRIs and TCAs in all countries except Poland in the inpatient setting, and Italy and Poland within the outpatient settings. The weighted average expected cost per patient varied from US$632 (Poland) to US$5647 (US) in the six-month acute phase treatment of MDD. The estimated total budgetary impact for each 1% of venlafaxine utilization, assuming a population of one million MDD patients, ranged from US$1600 (Italy) to US$29,049 (US). CONCLUSIONS: Within the inpatient and outpatient treatment settings, venlafaxine IR was a more cost-effective treatment of MDD compared to the SSRIs and TCAs. Additionally, the results of this investigation indicate that increased utilization of venlafaxine in most settings across Europe and the Americas will have favorable impact on health care payer budgets. ADR, adverse drug reaction; CMA, clinical management analysis; ECT, electroconvulsive therapy; HAM-D, Hamilton Depression Scale; MADRS, Montgomery-Asberg depression rating scale; MDD, major depressive disorder; SFD, symptom-free day; SNRI, serotonin-norepinephrine reuptake inhibitor; SSRI, selective serotonin reuptake inhibitor; TCA, tricyclic antidepressant; WHO, world health organization.
The effects of hexachlorobenzene (HCB) on the ability of male rats to adapt to a crowded environment were investigated. Eighty male rats were individually housed (1000 cm2 floor space per rat) and given either feed containing 250 ppm HCB or control feed. After 4 w, half of the rats from each diet group were transferred to smaller cages with four rats per cage (100 cm2 floor space per rat). After 1, 2, 4, 7, and 10 d, four rats each from the four treatment groups were sacrificed and organs removed for analysis. The HCB diet alone had no effect on the body weight of the rats. Crowding resulted in severe loss of body weight, an effect that was potentiated by the HCB diet. The HCB diet resulted in increased liver and kidney weight but had no effect on brain weight. Livers and kidneys of crowded rats weighed less than those of singly housed rats. Rats fed HCB then crowded had higher tissue residues of HCB and higher mortality than rats given HCB and not crowded or rats crowded but not given HCB.