Seventh Treatment Research Articles

Ibopamine in Patients with Congestive Heart Failure and Different Degrees of Renal Function.

Following a 1-week placebo run-in phase, 20 patients with congestive heart failure (New York Heart Association class II) were treated orally for 7 days with 100 mg ibopamine t. i. d. Ten subjects had a normal renal function, whereas 10 patients suffered from chronic renal insufficiency (mean creatinine clearance 36 plus minus 3.9 ml min(minus sign1)). Ibopamine significantly increased stroke volume and cardiac output, but only 45 and 90 min after administration. After 7 days of ibopamine treatment, urine output rose significantly in both patient groups by about 400--500 ml per 24 h. The glomerular filtration rate (inulin clearance) and urine osmolality remained nearly unchanged, whereas renal plasma flow (PAH clearance) increased on ibopamine administration. Urinary sodium and potassium excretion were slightly but insignificantly elevated. Pharmacokinetic parameters of ibopamine were unaltered in impaired renal function, both on the first and seventh treatment day. Maximum plasma levels of the active metabolite epinine were achieved after 45 min and were higher on the first as compared with the seventh treatment day in both groups. In conclusion, ibopamine caused a relevant increase in stroke volume and cardiac output associated with a rise in renal perfusion and urine output in patients with normal and with impaired renal function. Ibopamine is an orally active derivative of dopamine and is used for treatment of patients with congestive heart failure, who frequently have an impaired renal function. Therefore, in the present study, the hemodynamic effects and kinetic behavior of ibopamine should be investigated in patients with different degrees of renal function.

Flunixin in the cat: A pharmacodynamic, pharmacokinetic and toxicological study

There are relatively few non-steroidal anti-inflammatory drugs (NSAIDs) for which basic pharmacokinetic and toxicological data are available in the cat. This paper describes some pharmacokinetics and pharmacodynamics of flunixin in this species. Six healthy adult female cats were given 1.0 mg kg-1 flunixin meglumine orally daily for 7 consecutive days. Indwelling catheters were placed on the day preceding the first and last flunixin doses and 2 ml blood samples were taken for flunixin and thromboxane B2 (TXB2) assay before dosing and at 1, 2, 3, 5, 7, and 24 h after the first and the last doses of flunixin. Blood samples for haematology were taken before any treatment had been given and on treatment days 4 and 7 as well as 7 days after the end of treatment. On the first day of dosing, Cmax ranged from 0.45-6.94 micrograms ml-1 flunixin and the mean plasma concentration was greatest at 1 h (2.46 micrograms ml-1). No flunixin was detected by 24 h. After 7 days dosing, Cmax ranged from 0.47-2.46 micrograms ml-1. The mean plasma concentration was again greatest at 1 h but was lower (1.68 micrograms ml-1) than on the first day of treatment. No flunixin was detected beyond 5 h after dosing. The area under the plasma concentration time curve 0-24 h on the first day was 6.82 +/- 1.85 micrograms ml-1h-1 and 3.32 +/- 0.73 micrograms ml-1h-1 on the seventh day. On the first treatment day, serum TXB2 was inhibited by at least 75% in all post-treatment samples up to 7 h but on the seventh day it was reduced only at 1 and 2 h after dosing. Serum TXB2 was significantly higher on the seventh treatment day compared with the first at 3, 5 and 7 h after dosing. No abnormal clinical signs were seen and appetite was unaffected throughout the study. Most biochemical and haematological values remained within normal limits although alanine aminotransferase increased from 11.4-21.3 iu l-1 on day 7 without any other evidence of abnormality. The data suggest that the cats developed tolerance to flunixin although it is not known whether this was due to liver enzyme induction or reduced drug absorption. It is interesting that the cat, despite its reputation for inability to eliminate NSAIDs, has a relatively short flunixin half life and appears to develop tolerance to the drug.

Pharmacokinetic evaluation of enrofloxacin administered orally to healthy dogs

Summary Enrofloxacin was administered orally to 6 healthy dogs at dosages of approximately 2.75, 5.5, and 11 mg/kg of body weight, every 12 hours for 4 days, with a 4-week interval between dosage regimens. Serum and tissue cage fluid (tcf) concentrations of enrofloxacin were measured after the first and seventh treatments. The mean peak serum concentration occurred between 1 and 2.5 hours after dosing. Peak serum concentrations increased with increases in dosage. For each dosage regimen, there was an accumulation of enrofloxacin between the first and seventh treatment, as demonstrated by a significant (P = 0.001) increase in peak serum concentrations. The serum elimination half-life increased from 3.39 hours for the 2.75 mg/kg dosage to 4.94 hours for the 11 mg/kg dosage. Enrofloxacin accumulated slowly into tcf, with peak concentrations being approximately 58% of those of serum. The time of peak tcf concentrations occurred between 3.8 hours and 5.9 hours after drug administration, depending on the dosage and whether it was after single or multiple administrations. Compared with serum concentrations (area under the curvetcf/area under the curveserum), the percentage of enrofloxacin penetration into tcf was 85% at a dosage of 2.75 mg/kg, 83% at a dosage of 5.5 mg/kg, and 88% at a dosage of 11 mg/kg. All 3 dosage regimens of enrofloxacin induced continuous serum and tcf concentrations greater than the minimal concentration required to inhibit 90% (mic90) of the aerobic and facultative anaerobic clinical isolates tested, except Pseudomonas aeruginosa. Only the 11 mg/kg dosage regimen provided continuous serum and tcf concentrations that exceeded the mic90 for P aeruginosa isolates; whereas none of the dosages induced serum or tcf concentrations greater than the mic90 of the obligate anaerobic bacteria tested.

Hemodynamic Effects of Different H2-Receptor Antagonists

In a randomized, placebo-controlled, double-blind study, 10 healthy volunteers were treated orally once a day for 1 week each with placebo, 800 mg cimetidine, 300 mg ranitidine, and 40 mg famotidine. On the seventh treatment day, heart rate, blood pressure, systolic time intervals, and impedance cardiography were measured before the morning dose and at 2, 6, 12, and 24 hours after the morning dose. Heart rate and blood pressure were not markedly altered by any of the H2-receptor antagonists compared with the findings for placebo. Cimetidine and ranitidine did not markedly alter parameters of systolic time interval and impedance cardiography compared with placebo in contrast to famotidine, which significantly decreased stroke volume, cardiac output, and the Heather Index in impedance cardiography (p less than 0.05) and also significantly increased the ratio of the preejection period to the left ventricular ejection time in systolic time interval (p less than 0.05) 2 hours after the morning dose. Six hours after administration, most of these alterations could no longer be detected. The observed changes in hemodynamic parameters confirm that famotidine exerts negative effects on cardiac performance, whereas such influences could not be shown for cimetidine and ranitidine.

Effects of Alprazolam, Buspirone and Diazepam on Daytime Sedation and Performance

In a double-blind, randomised, comparative study, 44 healthy volunteers received alprazolam 0.5mg, buspirone 5mg or diazepam 5mg orally 3 times each day for 7 consecutive days. Daytime sedation was evaluated on the first and seventh treatment days by the multiple sleep latency test by direct EEG measurements. Sleep was recorded the night preceding each test day to control for the influence of sleep on subsequent daytime sedation and performance. A vigilance visual-tracking/reaction-time test was used to examine daytime performance, while other symptoms of daytime sedation were subjectively assessed by questionnaires. During treatment day 1, alprazolam- and diazepam-treated subjects were significantly sleepier than subjects who received buspirone. Compared with buspirone, performance was significantly impaired for the alprazolam subjects but not for the diazepam group. On day 7 differences in daytime sleepiness and sleep latency were no longer significant. However, alprazolam- and diazepam-treated subjects exhibited significantly slowed reaction times on the performance test. These results suggest that buspirone may have potential as an anxiolytic agent for patients in whom daytime alertness must not be compromised.

Research Note: Feeding Various Levels of Ground Sesbania macrocarpa Muhl. Seed to Bobwhite Quail

Two 28-day experiments were conducted to determine the effects of various levels of ground Sesbania macrocarpa Muhl. seed on mature bobwhite quail. In Experiment 1, S. macrocarpa Muhl. seed levels of 0, 1, 2, 3, 4, and 5% were added to a basal diet at the expense of filler and fed to five replicate groups of six 58-wk-old paired quail (one male and one female). Average daily feed consumption, hen-day egg production, average BW change, mortality, fertility, and natchability were monitored. Four groups of eight individually caged females, 63 wk of age, were each given a diet containing 0, 2, 4, 6, 8, or 10% ground S. macrocarpa Muhl. seed in Experiment 2. A seventh treatment was added that consisted of 10% ground S. macrocarpa Muhl. from an older seed shipment used previously in work with White Leghorn hens.Increasing S. macrocarpa Muhl. seed levels in Experiment 1 did not cause significant deviations from the control treatment for average daily feed consumption, BW change, hen-day egg production, fertility, total natchability, or hatchability of fertile eggs. In Experiment 2 neither average daily feed consumption nor hen-day egg production were affected by seed level or source. Quail given the 10% seed level using the older seed shipment had a significantly greater weight loss than the control birds. With the exception of this greater weight loss and in contrast with work involving chickens, dietary levels of ground S. macrocarpa Muhl. seed of up to 10% were acceptable to bobwhite quail.

Hemodynamic effects of different H2-receptor antagonists

In a randomized, placebo-controlled, double-blind study, 10 healthy volunteers were treated orally once a day for 1 week each with placebo, 800 mg cimetidine, 300 mg ranitidine, and 40 mg famotidine. On the seventh treatment day, heart rate, blood pressure, systolic time intervals, and impedance cardiography were measured before the morning dose and at 2, 6, 12, and 24 hours after the morning dose. Heart rate and blood pressure were not markedly altered by any of the H2-receptor antagonists compared with the findings for placebo. Cimetidine and ranitidine did not markedly alter parameters of systolic time interval and impedance cardiography compared with placebo in contrast to famotidine, which significantly decreased stroke volume, cardiac output, and the Heather Index in impedance cardiography (p less than 0.05) and also significantly increased the ratio of the preejection period to the left ventricular ejection time in systolic time interval (p less than 0.05) 2 hours after the morning dose. Six hours after administration, most of these alterations could no longer be detected. The observed changes in hemodynamic parameters confirm that famotidine exerts negative effects on cardiac performance, whereas such influences could not be shown for cimetidine and ranitidine.

Timing Lorsban Applications for California Red Scale Control, 1988

Abstract A randomized complete block experiment with 10 single-tree replicates and 7 treatments was conducted in a field of mature “Old Line Washington” navel orange trees in Field 63 at the University of California Lindcove Field Station, Exeter, California. Each experimental tree was surrounded on all 4 sides by untreated border trees. Trees were assigned to 10 blocks of 7 trees each based on their pre-treatment infestation level of CRS, so that the 7 trees within each block had similar pre-treatment infestations of CRS. Each of the 7 trees in each block then was assigned randomly to a treatment so that each treatment was represented once in every block. Six treatments were different application dates for Lorsban 4E at a dilution of 3/4 pt/100 gal. It was our original intention to apply all treatments in an identical manner, but our spray rig broke down half way through the experiment, and we had to use an alternate spray rig which was probably less effective than the first rig for obtaining good spray coverage. For this reason, results were compared only among treatments that were applied with the same spray rig. Applications by spray rig #1 were made at 460°520 psi and ca. 17-18 gal/tree and were applied with hand-held spray guns from both ground and tower (ca. 15-20 ft up) positions. Applications by spray rig #2 were made at 470 psi at ca. 19 gal/tree and were applied by hand-held spray guns from the ground only. The seventh treatment was an untreated control. The level of infestation of red scale in the plots was assessed once pre-treatment (Mar-Apr) and twice post-treatment (Dec, Mar 1989). In all 3 evaluations, 75 twigs (ca. 1-2 yr old, ca. 9 inch long)/tree were examined in situ and scored for the presence/absence of live CRS (only adult females were counted in the post-treatment evaluations while any stage except first instar was counted in the pre-treatment evaluation). In both post-treatment evaluations, up to 100 fruit/tree (100 were not always available, averages were 75 and 87 fruit/tree in the first and second post-treatment counts, respectively), were scored in situ as being infested with 0, 1°10, or >10 live or dead CRS (any stage). Infested fruit were categorized into those with more or less than 10 CRS/fruit because fruit generally are downgraded in the packinghouse when infested with approximately 10 or more scale. Also, both live and dead CRS are included in fruit evaluations because scaly fruit are downgraded in the packinghouse regardless of whether the scale are live or dead. Therefore, counts of live and dead CRS on fruit were used to assess how well a treatment protected the fruit from becoming infested and downgraded while counts of live CRS on twigs were used to assess how well a treatment suppressed population growth. During the 3.5 month period that encompassed all the application dates, red scale phenology was monitored weekly with pheromone traps and crawler traps.

Detachment of Soil as Affected by Fertility Management and Crop Rotations

AbstractAn experiment was initiated on Sharpsburg silty clay loam (fine, montmorillonitic, mesic Typic Argiudoll) in 1981 to compare the effects of fertility management and crop practices on splash detachment of soil. Experimental treatments included comparisons of crop rotations of soybean [Glycine max (L.) Merr.] after corn (Zea mays L.) (SB), corn after soybean (C), and oat/red and yellow sweetclover (Avena sativa L./Trifolium pratense L. and Mellilotus officinalis Lam.) after corn (O/CL). For each crop rotation, there were two management options, either added manure (OR) or herbicide plus chemical fertilizer (HF). The seventh treatment was continuous corn (CC) with herbicide, chemical fertilizer, and insecticide. Soil surface samples from each treatment were subjected to rainfall intensities of low (35 mm h−1), medium (62 mm h−1), and high (120 mm h−1). Total splash detachment of soil from simulated rainfall was linearly related to rainfall intensity. For all crop rotation treatments, total splash detachment generally was greater for manured soils than from soil with herbicides and fertilizer. Continuous corn had the lowest soil splash detachment at low intensity, second highest splash detachment at medium intensity, and the highest splash detachment at high intensity. This trend clearly indicated that rate of splash detachment of CC was higher than from soil under crop rotations. The splash detachment rates were 48, 40, 39, and 31 mg cm−3 for CC, C, SB, and O/CL, respectively. Treatment by rainfall intensity interaction was significant, which suggested that intensity and crop rotation were not independent in their effect on soil splash detachment. Soil aggregation as inferred from geometric mean diameter (GMD) indicated that CC had the lowest degree of aggregation (150) as compared to 211 for C, 225 for SB, and 313 for O/CL.

Apple, Evaluation of Fenoxycarb for Tabm Control, 1987

Abstract Experimental sprays were applied to 3-4 tree plots arranged in a randomized complete block design consisting of 6 replicates of alternating 'York Imperial' and 'Golden Delicious' trees. One 'York Imperial' and 'Golden Delicious' tree in the center of each plot was used for monitoring. All treatments were applied with a Friend Airmaster 393 airblast sprayer calibrated to leliver 50 gal/acre (complete spray), or 25 gal/acre, alternate-side spray, driven at 2.3 mph. The first 4 treatments were applied as complete sprays, whereas I he fifth, sixth, and seventh treatments were applied as alternate-side sprays. Dates of application were as follows: first and second treatments on 11 and 22 May, 20 and 29 Jul; third and fourth treatments on 1 and 15 Jun, 29 Jul, and 13 Aug; the fifth, sixth, and seventh treatments 1, 8, 15, and 22 Jun, 29 Jul, 7, 13, and 20 Aug. On 3 Jun an alternate-side application of Lannate 1.8L (710 ml/acre) was applied to all plots to control periodical cicada. Phosphamidon SEC (237 ml/acre) was applied as alternate side applications to all treatments on 6, 13, and 23 Jun and 10 Jul to control aphids. Vydate 2L (710 ml/acre) plus Carzol 92SP (227 g/acre) and Plictran 50WP (680 g/acre) were applied on 10 and 17 Jul, respectively, as alternate-side sprays to control mites. During the experiment, general maintenance sprays of Dithane M-45 and calcium chloride were applied to all treatments. Effect of treatments on ERM was evaluted by counting the mites several times during the season on samples of 25 leaves/tree ('York Imperial' only), 150 leaves/treatment. Effect of treatments on the mite predator S. punctum was evaluated by 3-min counts of adults and larvae around the periphery of the test trees. Effectiveness of treatments on TABM was assessed by scoring for injury all apples on the center 'Golden Delicious' and 'York Imperial' trees at harvest and on all drops up to harvest. Pest pressure was moderate.

Isolation of a high yielding alkaline protease variant of Bacillus licheniformis

A high yielding stable variant of Bacillus licheniformis has been isolated to secrete 100% more activity of alkaline protease by growing the wild type in a medium containing 5% glucose and by subjecting it to repeated heat (80°C, 30 min) treatment. After the seventh treatment, alkaline protease activity had increased from 85 to 196 U ml −1, offering reproducible performance for commercial exploitation.

Varietal Responses in Spring Barley to Natural and Artificial Lodging and to a Growth Regulator

SUMMARYEight varieties of spring barley differing in their morphology and resistance to lodging were grown in a trial as main plots which were split for seven treatments: a natural control (C), a control with plots which were mechanically supported (S) and four artificially induced lodging treatments: permanent early lodging (PEL); temporary early lodging (TEL); permanent late lodging (PLL) and temporary late lodging (TLL). The seventh treatment (GR) was an application of the growth regulator BAS 09800W. In comparison with S, treatments PEL, TEL, PLL and TLL reduced grain yield by 38–1, 24–8, 22–0 and 13–9 % respectively. Natural lodging in C plots reduced the yield of the two weakest strawed varieties, Guilden and Jupiter, by 8 and 10% respectively in comparison with treatment S. Yields (C) of these two varieties were increased by GR which had no effect on the yield of other varieties, but reduced grain size in some cases. Treatment GR significantly reduced but did not eliminate natural lodging in weaker strawed varieties and reduced the length of the top four internodes. Lodging reduced grain size in terms of 1000–grain weight and sieving fractions and increased the content of husk and protein. Lodging susceptibility was positively correlated with plant height but showed no clear relationship with the number of vascular bundles, stem diameter, wall thickness, or with the content of lignin, cellulose and hemicellulose in the basal internodes. Lodging resistance appeared to be closely associated with short basal internodes.

Synthetic Pyrethroids for Worm Control on Head Lettuce, 1975

Abstract Great Lakes 659 lettuce was planted August 25, 1975 on 40-inch beds, 2 seed rows per bed. Plots were four beds wide and 25 feet long or 0.0076 acres. Three materials were tested at 0.05 and 0.1 lb per acre and each treatment was replicated four times in a randomized block design. All treatments were compared to a standard (Lannate) and an untreated check. All plots received an application of Lannate* t at 0.67 lb a.i./a on September 8, 1975 to protect the stand of seedling lettuce prior to thinning. The first scheduled test treatments were applied September 16 and weekly thereafter, with the seventh and final treatment being applied on October 28. All treatments were applied with a 3 gallon pressure-type sprayer having a two nozzle boom operating at 45 to 55 psi. Effectiveness of the various treatments was determined by counting the number of cabbage looper and beet armyworm larvae and eggs on 20 plants per plot on a weekly schedule. The worm population was very high during the early part of the growing season necessitating another treatment of Lannate on the check plots. Many plants in the check plots had been so badly damaged that only the midribs of the leaves remained. Most of these plants recovered, but maturity was delayed 1 to 3 weeks.

The effect of repeated applications of heat on spermatogenesis in the rat: a histological study.

Summary. The effect of repeated exposures of rat testes to 43·5° C has been studied, allowing a 6-week recovery period between treatments. Following exposure to heat, the weight of the testes was lower than in normal males, even in the twelve males which recovered fertility within 24 weeks following the seventh treatment. No significant changes were found in seminal vesicle weight. Seminiferous tubules were either normal in histological appearance, or showed 'partial' or 'severe' damage 6 weeks after each application. The percentage of 'severely' atrophic tubules increased by about 4% with successive heatings. It is concluded that such damage occurred in tubules in which stem cells were dividing at the time of heating and that, as a consequence, their regenerative capacity was severely impaired.

GEOPHYSICAL RESEARCH & PROGRESS IN EXPLORATION, 1965–1968

This is a progress report on developments in geophysical research and progress in exploration during the time interval from 1965 to 1968. It is the seventh treatment of this type prepared by the members of the society in the past 13 years.

STUDIES IN ELECTRONARCOSIS THERAPY

1. Electronarcosis has been administered to a group of 53 mentally ill persons. The results of follow-up studies one month after treatment was completed may be summarized as follows: 37 cases of schizophrenia were treated, 7 recovered; 9 cases of psychoneurosis were treated, none recovered; 7 cases of manic-depressive psychosis were treated, 2 recovered. However, if one includes only cases that received 7 or more treatments, the results one month after treatment would read as follows: 31 cases of schizophrenia were treated, 5 recovered; 5 cases of psychoneurosis were treated, none recovered; 4 cases of manic-depressive psychosis were treated, 1 recovered. 2. Of the 5 schizophrenic patients who received 7 or more treatments and recovered, improvement was noted at some time between the second to seventh treatment. 3. It is our impression that electronarcosis is of no value in the treatment of psychoneurotics, is certainly no better than electroshock in treating the manic-depressive psychoses, and is equal to electroshock in the treatment of schizophrenia. Our series are too small for any definite conclusions to be drawn, and the above estimation of the value of electronarcosis therapy is subject to revision after we have treated a larger series of cases. 4. Fractures of the spine occurred in 15 of the 53 patients treated, amounting to 28.3% of the cases. This percentage can be greatly reduced by the use of sodium amytal or by the new Glissando technique recently developed by Tietz. 5. Because of the extreme rise in blood pressure that occurs during treatment, electronarcosis should not be used on patients with hypertension or cardiac disease. 6. Electronarcosis is a more dangerous treatment than electroshock and is less simple to administer.

NEW YORK ACADEMY OF MEDICINE, SECTION OF NEUROLOGY AND PSYCHIATRY

Artificial hyperthermia has been employed with increasing frequency in the treatment of various neurologic disorders. There are numerous observations on the biochemical alterations during artificial hyperthermia, but hardly any note has been made of the neurologic manifestations. Reports in the literature of post¬ mortem observations on patients succumbing during or shortly after hyperthermia have demonstrated that there are profound neuropathologic changes which explain the neurologic signs and symptoms appearing during the treatment. Recently, at the Neurological Institute of New York, attention was focused on the transitory neurologic changes which occurred in a patient with multiple sclerosis during electropyrexia. A white man aged 21 received eleven treatments in the vapotherm, during each of which the temperature was elevated to 104 F. for three hours. During the sixth and seventh treatments he complained of numbness in both hands, and during the eighth, of a sensation of pins and needles in the hands and feet. These dysesthesias increased until, during the tenth and eleventh treatments, there developed paralysis in all four extremities. Between treatments the symptoms receded. Examination during the eleventh treatment showed : flaccid paralysis of the legs and arms ; complete anesthesia to all modalities in the legs up to and including the twelfth thoracic dermatome, with the exception of the third, fourth and fifth sacral areas, over which there was partial preservation of superficial sensation ; complete anesthesia to all modalities in the arms between the fifth cervical and the second thoracic dermatome ; complete areflexia of the arms and legs; diminished abdominal reflexes, and a positive Babinski sign (not previously present) on the left. The temperature was allowed to drop and within forty-five minutes reached 99 F. Neurologic examination showed partial return of motor power in all extremities, the proximal joints showing more strength than the distal. Deep sensation had returned to the pretreatment state, but there was still definite hypesthesia to superficial stimulation. Reflexes had returned almost to the pre¬ treatment status. The Babinski sign had disappeared. That night the patient was up and felt well. On examination his status was found to have returned to the pretreatment level. For fear of producing irreversible neurologic changes, hyperthermia was discontinued, and he was discharged on May 28, 1938. When seen on August 9, he stated that he was feeling fine, that vision had improved considerably, that the numbness had disappeared from his hand and that his gait was much improved. During a preceding two weeks of hot, humid weather he said that his symptoms had recurred, but they disappeared with cooler weather. Further examination on September 9 revealed a status similar to that on admission except for more marked difficulty in gait and a positive Romberg sign. The literature is silent on transitory neurologic changes during artificial hyper¬ thermia. Occurrence of such changes during hyperthermia from malaria and other biologic agents has been reported. However, in these reports there are to be considered the factor of the infectious agent and its effect on the nervous system.