Biomedical subjects
Publications and source records attributed to C Marshall.
Ten Alzheimer's disease patients underwent a trial of oral tetrahydroaminoacridine (THA) and lecithin. After 3 inpatient weeks there was no clear therapeutic effect. Three of six patients able to continue in long-term treatment showed measurable cognitive improvement, but only one displayed clinically obvious improvement.
The effect of almitrine bismesylate on the hypoxic pulmonary vasoconstrictor response was studied in six closed-chest dogs anesthetized with pentobarbital and paralyzed with pancuronium. The right lung was ventilated continuously with 100% O2; the left lung was ventilated either with 100% O2 ("hyperoxia") or with an hypoxic gas mixture ("hypoxia": end-tidal oxygen tension = 60.3 +/- 0.6 mm Hg). On two consecutive days, each dog received either almitrine (Vectarion, Servier Lab) or malic acid. Consecutive almitrine doses of 0.003, 0.03, 0.3, and 3.0 micrograms.kg-1.min-1, or the equivalent volumes of malic acid without almitrine, were administered intravenously as a constant peripheral infusion for 15 min. Percent blood flow to each lung was calculated based on a variation of the traditional shunt equation. The change in percent left lung blood flow (delta %QL-VA) increased significantly between the hypoxia-no drug and the hypoxia-almitrine (3.0 micrograms.kg-1.min-1) phase. No significant changes occurred during the other almitrine doses or the respective malic acid control phases. The change in arterial oxygen tension (delta PaO2) also increased significantly between the hypoxia-no drug and the hypoxia-almitrine (3.0 micrograms.kg-1.min-1) phase. No significant changes occurred during the other almitrine doses or the respective malic acid control phases. It is concluded that in dogs low-dose almitrine enhances hypoxic pulmonary vasoconstriction and that this enhancement is dose-related.
Three dogs showed signs of intravascular haemolysis, spherocytosis and peripheral neuropathy following severe bee envenomation. These effects were ascribed to the constituents of bee venom, especially melittin and phospholipase A. All 3 cases recovered and were discharged subsequent to prednisolone and supportive therapy.
Selected haematological, blood chemical and serological variables were investigated in healthy Thoroughbreds (n = 45) in training. Haemoglobin concentration, haematocrit, red, white and differential cell counts as well as serum concentrations of total and ionized calcium, sodium, potassium, chloride, urea, creatinine, total protein, albumin, inorganic phosphorus, total bilirubin, iron, glucose, magnesium, alkaline phosphatase, gamma-glutamyltransferase, lactate dehydrogenase, aspartate transaminase, alanine transaminase and creatine kinase were found to be within ranges previously reported for horses. No statistically significant difference was found between the haematocrit (Ht) of horses n = 44; mean = 0.44; SD = 0.02) of different performance or between those of different age groups. A significant difference was found between the Ht of males (mean = 0.43; SD = 0.02) and females (mean = 0.45; SD = 0.02) and between quiet (mean = 0.44; SD = 0.02) and excitable (mean = 0.46; SD = 0.02) horses. No significant difference in red cell potassium concentration was found between horses of different performance. Cortisol, insulin, parathormone (C-terminal), aldosterone and folate concentrations respectively varied between 89-204 (mean = 144.4; SD = 25.47) nmol l-1, 4.2-23 (mean = 10; SD = 4.30) m U l-1, 65.2-91.4 (mean = 79.46; SD = 9.34) pmol l-1, less than 138 to 379 pmol l-1 and 9.4-21.5 (mean 14.5; SD = 2.87) nmol l-1. Vit B12 concentrations exceeded 1400 pmol l-1. Blood lead concentrations in all animals were below 15 ug l-1. Fifteen (33.3%) of the horses were carriers of babesiosis. Laboratory findings concerning these horses did not differ from those of the other horses.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The contribution of mechanical factors to the vascular resistance of the atelectatic lung has been studied in vivo in the anesthetized open-chest dog. When the left lung was ventilated with an hypoxic gas mixture (while the right lung was ventilated with 100% O2), left lung blood flow decreased from 0.99 +/- 0.11 1.min-1 to 0.40 +/- 0.08 1.min-1 due to hypoxic pulmonary vasoconstriction (hypoxic stimulus PSO2 = 36.1 +/- 0.8 mmHg). When the left lung was made atelectatic, blood flow decreased to 0.65 +/- 0.11 1.min-1, consistent with a weaker hypoxic stimulus (PSO2 = 54.0 +/- 3.2 mmHg). With the addition of sodium nitroprusside infused intravenously, left lung blood flow increased to 1.05 +/- 0.14 1.min-1 during atelectasis, and to 0.61 +/- 0.09 1.min-1 during hypoxic ventilation, while flow remained at 0.94 +/- 0.18 1.min-1 during hyperoxic ventilation. When the results were plotted on pressure-flow diagrams, the hyperoxic, hypoxic, and atelectatic lung points fell on the same pressure-flow line in the presence of nitroprusside. It is concluded that hypoxic pulmonary vasoconstriction is the major (but not necessarily only) determinant of increased vascular resistance in the atelectatic lung, and that passive mechanical factors do not measurably affect blood flow distribution during open-chest atelectasis.
A marked variability in serum phenytoin concentrations was observed in an elderly nursing home resident. To determine the prevalence of this problem, 15 frail nursing home patients who were receiving phenytoin therapy were studied over a mean follow-up period of 10.6 +/- 0.89 months. The mean number of serum phenytoin level measurements during this period was 13.1 +/- 1.5. For a given individual, there was no variation in phenytoin dose or preparation administered. All the patients had a difference of more than 50% between the highest and the lowest serum phenytoin levels, and in five patients (33%), the difference exceeded 150%. The change in serum phenytoin level was temporally related to influenza vaccination in only three patients. The form of phenytoin was not a significant determinant of the variability in this patient population, nor did enteral feeding have any effect. It is recommended that nursing home patients receiving phenytoin therapy have periodic serum phenytoin measurements obtained, even in the absence of seizures or classic signs of phenytoin toxicity.
Amikacin, clindamycin, gentamicin, Linco-Spectin, minocin and tylosin were added individually and in combinations at various concentrations to bovine neat semen and to egg-yolk citrate, egg yolk-tris or heated whole milk extenders (nonglycerol fractions) prior to final processing for freezing to -196 degrees C. After thawing samples, seminal quality was measured by progressive motility and acrosomal integrity evaluations. Studies were performed in parallel with microbiological efficacy studies of Shin et al. (7). The antibiotic combination including gentamicin, tylosin and Linco-Spectin at 500 ug/ml, 100 ug/ml and 300/600 ug/ml, respectively, was not detrimental to seminal quality and, in the parallel studies, was most efficacious in controlling microorganisms potentially present in bovine semen.
Field fertility (nonreturn rate) studies were performed independently by three artificial insemination organizations to evaluate bovine semen processed for freezing using the antibiotics gentamicin, tylosin and Linco-Spectin at concentrations of 500 ug, 100 ug, and 300/600 ug, respectively, per milliliter of neat semen and per milliliter of nonglycerol portion of the extender. The antibiotic combination including penicillin, dihydrostreptomycin, polymyxin B sulfate, with/without Linco-Spectin (500 units/ml, 2000 ug/ml, 1000 units/ml and 300/600 ug/ml, respectively) was used as the control treatment. Results indicated no significant effect on seminal quality as measured by field fertility under the conditions of these experiments using heated whole milk or egg yolk-sodium citrate seminal extenders. Use of the new antibiotic combination has been adopted by Certified Semen Services.
The effect of prostaglandin F2 alpha (PGF2 alpha) on the hypoxic pulmonary vasoconstrictor (HPV) response was studied in 12 closed-chest dogs anesthetized with pentobarbital and paralyzed with pancuronium. The right lung was ventilated continuously with 100% O2, while the left lung was either ventilated with 100% O2 ("hyperoxia") or ventilated with an hypoxic gas mixture ("hypoxia:" end-tidal PO2 approximately equal to 50.0 +/- 0.1 mmHg). Cardiac output (CO) was altered from a "normal" value of 2.89 +/- 0.26 1.min-1 to a "high" value of 3.55 +/- 0.26 1.min-1 by opening arteriovenous fistulae which allowed measurements of two points along a pressure-flow line. These four phases of left lung hypoxia or hyperoxia with normal and high cardiac output were performed in the absence of, and in the presence of, PGF2 alpha administered as a constant peripheral intravenous infusion of 1.0 microgram.kg-1.min-1. During left lung hypoxia, mean pulmonary artery pressure (PAP) increased significantly when compared to hyperoxia. With PGF2 alpha administration, mean PAP increased significantly during both hyperoxia and hypoxia. The presence or absence of PGF2 alpha had no effect on cardiac output or PaO2 during hypoxia. Relative blood flow to each lung was measured with a differential CO2 excretion (VCO2) method corrected for the Haldane effect. With both lungs hyperoxic, the percent left lung blood flow (%QL-VCO2) was 45 +/- 1%. When the left lung was exposed to hypoxia, the %QL-VCO2 decreased significantly to 29 +/- 3%. However, with the administration of PGF2 alpha, the %QL-VCO2 during left lung hypoxia did not change significantly 26 +/- 3%.(ABSTRACT TRUNCATED AT 250 WORDS)
The detailed anatomic and biodynamic data provided for the cat lung by Zhuang et al. (J. Appl. Physiol. 55: 1341-1348, 1983) allowed pressure-flow curves for the normal lung to be generated. This model has been modified to permit the stimulation of the pressure and flow distribution effects of hypoxic pulmonary vasoconstriction for a two-compartment lung and generalized to allow comparison with the experimental results from dogs (and probably other species). Hypoxic pulmonary vasoconstriction is simulated by reduction of the initial diameter of the smallest six orders of pulmonary arteries. Expressions are presented that relate the alveolar and mixed-venous O2 tensions to a graded constriction of these vessels. In addition, the diameter of the capillary sheet and the six small arteries is defined with a maximum diameter at a transmural pressure of 20 cmH2O. Pressure-flow curves are derived for any combination of alveolar and mixed-venous O2 tension, alveolar and pleural pressure, left atrial pressure, and hematocrit. The two-compartment model is solved by an iterative procedure to identify the distribution of the flow and the resulting pulmonary arterial pressure when the compartments differ by size, hypoxic constriction, or other imposed conditions. The results of the model are compared with those from a variety of experimental preparations. It is concluded that the model is useful for identifying the quantitative causes of changes in the response to hypoxic pulmonary vasoconstriction and for the exploration of the functional influence of mechanical properties of the vasculature.
The mechanism responsible for initiating hypoxic pulmonary vasoconstriction (HPV) remains controversial. In this study, reversible constriction of the pulmonary artery was produced when the ratio of carbon monoxide to oxygen was increased, demonstrating that HPV could be imitated even in the presence of a constant oxygen tension. Isolated rat lungs from 14 adult rats were perfused with a 5% albumin-physiological salt solution and ventilated with 21% O2, 5% CO2, balance N2. At the end of a 30-min stabilization period, the lungs were injected with a bolus of angiotensin II (0.2 micrograms). They were then challenged three times for 5 min with an hypoxic gas mixture alternating with 5 min of normoxia. The ventilatory circuit was then changed to one in which 10% O2, 5% CO2 and varying concentrations of CO (balance N2) could be administered. The concentration ratios of CO:O2 were 0.5:1, 1:1, 2:1, 4:1, and 8:1. These were randomly administered for 6 min interspersed with 6 min of normoxia; a final angiotensin II challenge was given. The results show a slight but significant vasodilation with CO:O2 of 0.5:1, 1:1 with mean depressor responses of 0.7 +/- 0.1, -0.7 +/- 0.1 cm H2O and progressive vasoconstriction with CO:O2 of 2:1, 4:1, 8.5:1 with mean pressor responses of 0.11 +/- 0.3, 4.0 +/- 0.4 and 6.2 +/- 0.5 cm H2O. The pressor response to angiotensin II remained unchanged from beginning to end (9.5 +/- 0.5, 8.1 +/- 0.7 cm H2O. The pressor responses, therefore, are consistent with reduced function of the cytochromes of the electron transport chain. These results suggest that HPV may be initiated by a reduction of energy state of the vascular smooth muscle and that postulation of a specific oxygen receptor is not necessary.
A model has been developed which allows an isolated lung to be perfused by a blood-PSS solution continuously processed by an intact animal. This model combines the advantage of control of the isolated perfused lung with a recirculated perfusate that is physiologically maintained. Substances that are generated by the isolated lung are, therefore, removed by metabolism in the intact animal and essential consumables in the perfusate are restored. Studies were performed in rabbits utilizing isolated perfused lung both with and without the intact animal processing the perfusate. The greatest pressor responses to hypoxic ventilation are obtained with a non-processed recirculated perfusate circuit, but the pressor responses decrease with time (12.5 +/- 1.7 cmH2O to 8.2 +/- 1.3 cmH3O) and the baseline pressure is higher initially (18.5 +/- 0.7 mmH2O). With the whole animal in the circuit, the baseline pressure and the initial hypoxic pressor responses are not as large, but are maintained constant (6.8 +/- 0.5 cmH2O to 8.1 +/- 1.0 cmH2O) over the same time period. When the isolated lungs are perfused with either blood-PSS or PSS in a non-processed, non-recirculated system, the hypoxic responses are 8.7 +/- 1.7 cmH2O and 5.7 +/- 1.0 cmH2O at the beginning of the study and decrease with time to 6.5 +/- 1.3 cmH2O and 4.2 +/- 1.0 cmH2O, respectively. The response of the isolated lung is, therefore, more stable with time and shows less individual variability when the whole animal perfusion circuit is employed.
The effect of intrapleural pressure on the hypoxic pulmonary vasoconstrictor (HPV) responses to atelectasis and hypoxia were measured in two groups of anesthetized closed chest dogs. The right lung was continuously ventilated with 100% O2. The left lung was initially ventilated with 100% O2 (hyperoxia) but subsequently underwent either reabsorption atelectasis (atelectasis; group I) or ventilation with a hypoxic gas mixture (hypoxia; group II). The mean intrapleural pressure in the left hemithorax was 5.4 cm H2O during hyperoxia, but with left lung atelectasis decreased significantly to -3.8 cm H2O by 15 minutes and to -4.2 cm H2O by 90 minutes. Venous admixture (% VA) increased significantly from 10.3% during hyperoxia to 33.2% at 15 minutes of left lung atelectasis and to 34.6% at 90 minutes. However, after sternotomy with the left lung still atelectatic, the %VA decreased significantly to 25.4% For the hypoxia group, %VA increased significantly from 9.2% during hyperoxia to 29.9% at 15 minutes of left lung hypoxia and 25.1% at 90 minutes. HPV diverted blood flow away from both atelectatic lung and hypoxic lung. However, due to the negative intrapleural pressure generated during left lung resorption atelectasis when the chest was closed, HPV was less effective during atelectasis than during hypoxia.
To investigate whether the activated N-ras oncogene of HT1080 human fibrosarcoma cells contributes to the expression of the transformed phenotype, we have isolated flat revertants. In two independent revertant lines, an increase in chromosomal ploidy occurred without a concomitant increase in the number of copies of the N-ras transforming allele. Immunoprecipitation confirms that the level of the mutant N-ras p21 gene product in the revertants is correspondingly lower than in HT1080. Analysis of sporadic tumors derived from the revertant cells reveals an increased dosage of the transforming allele. The revertants also retransform after transfection of cloned activated ras oncogenes. These results imply direct participation of an N-ras oncogene in maintaining the transformed phenotype of a human tumor cell line.
The effect of halothane on the pressor responses to hypoxia (3% O2, 5% CO2, balance N2) and to Angiotensin II (Ang II) (0.2 microgram) has been compared in an in vitro perfused and ventilated rat lung preparation in the presence and absence of agents known to block the lipoxygenase (BW755C) and/or the cyclooxygenase (ibuprofen) pathways for arachidonic acid metabolism. Preliminary studies established the stability of the preparation (experiment 1) during two hours of observation and allowed estimation of (experiment 2) the concentration of BW755C that inhibited the HPV response by 50% (ED50 = 125 microM). In experiment 3, the rat lungs were subdivided into four groups: A, B, C, and D. Group A received the drug solvent, and B received 17 microM ibuprofen. Groups C and D received ibuprofen and, in addition, an ED50 dose of BW755C. The lungs were then tested for their response to hypoxia. In addition, groups C and D were tested for their response to 0.2 microgram Ang II. 0.5 MAC halothane was introduced into the ventilatory circuit of A, B, and D. Group C received no halothane. Responses to hypoxia and Ang II (groups C and D) were measured. Halothane was terminated and a further hypoxic response was tested in groups A and B. The results show, in group A, that the addition of halothane reduced the response to hypoxia from (mean +/- SE cm H2O) 13.4 +/- 1.56 to 6.5 +/- 1.28, a 50% reduction. The addition of ibuprofen in group B caused a 33% increase in the response, and the addition of halothane now caused only a 30% decrease.(ABSTRACT TRUNCATED AT 250 WORDS)