Use of collateral airways to assess airway reactivity

1991 ◽  
Vol 70 (1) ◽  
pp. 349-356 ◽  
Author(s):  
D. H. Corddry ◽  
R. A. Sauder ◽  
G. G. Weinmann ◽  
C. A. Hirshman ◽  
W. Mitzner
Keyword(s):  
Dose Response ◽  
Gas Flow ◽  
Response Curves ◽  
Airway Reactivity ◽  
Resistance Response ◽  
Peripheral Airways ◽  
Lung Segment ◽  
Peripheral Airway ◽  
The Mean ◽  
Dose Response Curves

We investigated the correlation between collateral airway reactivity and other indexes of lung reactivity in response to aerosol and intravenous (iv) challenges. In four anesthetized mongrel dogs, we measured the peripheral airway resistance (Rp) to gas flow out of a wedged lung segment in different lobes on multiple occasions. We obtained dose-response curves of peripheral airways challenged with iv histamine or aerosols through the bronchoscope. During the same iv bolus challenge, whole lung airway pressure (Paw) responses to histamine were also measured. On separate occasions, changes in lung resistance (RL) were measured after the whole lung was challenged with a histamine aerosol. Reactivity was assessed from the dose-response curves for Rp and RL as the PD50 (dose required to produce a 50% increase); for changes in Paw we calculated the PD15 (dose required to produce a 15% increase over baseline). Results for Rp showed considerably more variability among different lobes in a given animal with the aerosol challenge through the bronchoscope than with the iv challenge. With aerosol challenge there were no significant differences in the mean PD50 for Rp among any of the animals. However, with the iv challenge two of the dogs showed significant differences from the others in reactivity assessed with Rp (P less than 0.01). Moreover, the differences found in the peripheral airways with iv challenge reflected differences found in whole lung reactivity assessed with either iv challenge (Paw vs. Rp, r2 = 0.96) or whole lung aerosol challenge (RL vs. Rp, r2 = 0.84). We conclude that the measurement of the collateral resistance response to iv challenge may provide a sensitive method for assessing airway reactivity.

Dose-response curves of central and peripheral airways to nicotine injections in dogs

1986 ◽  
Vol 61 (5) ◽  
pp. 1677-1685 ◽  
Author(s):  
M. Nakamura ◽  
T. Haga ◽  
M. Miyano ◽  
H. Sasaki ◽  
T. Takishima
Keyword(s):  
Dose Response ◽  
Airway Resistance ◽  
Suppressive Effect ◽  
Response Curves ◽  
Parasympathetic Ganglia ◽  
Peripheral Airways ◽  
Peripheral Airway ◽  
Anesthetized Dogs ◽  
Vagal Reflex ◽  
Dose Response Curves

The dose-response curves of the central and peripheral airways to intravenously injected nicotine were studied in 55 anesthetized dogs. With intact vagi, nicotine caused a dose-dependent increase in central airway resistance (Rc) similar to the increase in peripheral airway resistance (Rp) at concentrations ranging from 4 to 64 micrograms/kg. However, the responses of both Rc and Rp fell progressively when sequential doses of nicotine greater than 256 micrograms/kg were administered. With intact vagi and the administration of propranolol, there was a greater increase in Rp than in Rc at a nicotine dose of 64 micrograms/kg (P less than 0.05). With vagotomy, the responsiveness of both central and peripheral airways to nicotine decreased with doses of nicotine less than 64 micrograms/kg, but with doses of nicotine greater than 256 micrograms/kg the suppressive effect of nicotine on both Rc and Rp was less than that seen with intact vagi. Under conditions in which the vagi were cut and atropine administered, the responsiveness of nicotine was even further depressed. Combinations either of atropine and chlorpheniramine or atropine and phenoxybenzamine also completely blocked reactions to nicotine. Additionally reactions to nicotine were completely blocked by hexamethonium. These results suggest that nicotine increases both Rc and Rp mainly through a vagal reflex and stimulation of the parasympathetic ganglia.

Quantitative estimates of the effects of concomitant chemotherapy on acute dysphagia in patients receiving radical treatment for head and neck cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22134-e22134
Author(s):  
S. Bhide ◽  
S. Gulliford ◽  
R. A'Hern ◽  
E. Hall ◽  
K. Newbold ◽  
...  
Keyword(s):  
Head And Neck Cancer ◽  
Radiation Dose ◽  
Head And Neck ◽  
Neck Cancer ◽  
Dose Response ◽  
Concomitant Chemotherapy ◽  
Response Curves ◽  
Pharyngeal Mucosa ◽  
The Mean ◽  
Dose Response Curves

e22134 Purpose: To generate quantitative parameters describing the effect of concomitant chemotherapy on incidence of grade 3 dysphagia (CTCAE v3.0, assisted feeding) using dose response curves in patients receiving radical treatment for head and neck cancer. Methods: Patients treated at a single centre in prospective phase I and II trials of concomitant chemo-IMRT (CRT) (n=85) and the phase III trial of IMRT vs. conventional radiotherapy (PARSPORT) (n=82) formed the basis of this non-randomized comparison. Patients in the PARSPORT trial received radiation alone (RT). Radiation dose for all patients was radiobiologically equivalent to at least 70Gy in 35 fractions. Concomitant chemotherapy was cisplatin (100 mg/m2) on days 1 and 29. G3 dysphagia was recorded prospectively. Dose volume histograms (DVH) were generated for the pharyngeal mucosa. The mean dose (converted to equivalent dose in 2Gy/fraction, MD2) was used as a univariate descriptor of the DVH, for the generation of the dose response curves. A logistic function of the form p=1/[1+(MD50/D)k] was fitted where, p is the probability of the incidence of toxicity, D is the mean dose, MD50 is the mean dose at which 50% of patients experience toxicity and k describes the increase in incidence with increasing dose. The dose response curves were fitted using non-linear logistic regression. Results: The mean MD2 to the pharyngeal mucosa were 56Gy and 55.8Gy respectively, in the CRT and RT groups. There was a statistically significant difference of 25% (95% CI: 10–38, p=0.002) in the incidence of G3 dysphagia between the CRT (68%) and RT (43%) groups. Fitting dose response curves to the clinical data yielded parameter values (95% CIs) of MD50=46 Gy (42–49), k=4.8 (2.3–7.2) for the CRT group and MD50= 58 Gy (55–61), k=3 (1.6-.45) for RT group. Dose response gradients for CRT and RT showed approximately 1.95% and 1.3% increase (respectively) in probability of G3 dysphagia resulting from an increase in mean dose of 1Gy between doses of 30Gy to 70Gy. Conclusions: Addition of concomitant chemotherapy increases the incidence of G3 dysphagia by 0.65% for every 1 Gy increase in radiation dose. The observed MD50 for G3 dysphagia is lower for RT alone (46 Gy vs. 58 Gy). No significant financial relationships to disclose.

Factor VIII-Related Activities in therapeutic concentrates

1979 ◽  
Author(s):  
T.W. Barrowcliffe ◽  
G. Kemball-Cook ◽  
G. Morris ◽  
J.C. Holt ◽  
I.R. Peake
Keyword(s):  
Factor Viii ◽  
Dose Response ◽  
Wide Spectrum ◽  
Parallel Line ◽  
Response Curves ◽  
Crossed Immunoelectrophoresis ◽  
Plasma Response ◽  
High Dilutions ◽  
The Mean ◽  
Dose Response Curves

Levels of Factor VIII clotting activity (VIII:C), VIII clotting antigen (VIII: CAg), VIII related antigen (VIII R:Ag) and ristocetin co-factor (RCF) have been compared in several batches of the various concentrates used therapeutically in the U.K. The mean ratio of VIII R:Ag to VIII:C ranged from 2 to 4, but a major problem in VIII R:Ag assays of concentrates against a plasma standard was non-parallelism of the dose-response curves. This reflects the abnormality of the antigen in the concentrates, as shown by its more rapid mobility on crossed immunoelectrophoresis. Ratios of VIII: CAg to VIII:C ranged from less than 1 to about 2; the higher ratios indicate denaturation of the clotting part of the molecule during purification. All concentrates had RCF levels at least equivalent to their clotting activity, but lower than their VIII R:Ag levels. At high dilutions, most concentrates gave an acceptable parallel line bioassay against a plasma standard, but as the concentration of ristocetin co-factor was increased, non-parallelism was observed, due to a failure of the plasma response to increase with increasing dose. In treatment of patients with haemophilia and von Willebrand’s disease, it should be recognised that concentrates which are equivalent in VIII:C potency may nevertheless display a wide spectrum of other Factor VIII-related activities.

Temporal and regional variability of collateral resistance response to histamine

1988 ◽  
Vol 64 (5) ◽  
pp. 2142-2149 ◽  
Author(s):  
M. S. Ludwig ◽  
S. A. Shore ◽  
K. Anderson ◽  
J. M. Drazen
Keyword(s):  
Dose Response ◽  
Coefficient Of Variation ◽  
Geometric Mean ◽  
Base Line ◽  
Response Curves ◽  
Regional Variability ◽  
Resistance Response ◽  
Dose Response Curves

Using the wedged bronchoscope technique, we measured the changes in collateral resistance (Rcoll) in dogs resulting from exposure to aerosols of increasing concentrations of histamine. Histamine dose-response curves were performed in each of two to three separate lobar segments of an individual mongrel dog's lungs. Five dogs were studied. The same segments were reexamined on later occasions (2–11 wk apart) to determine whether the responsiveness to histamine had altered with time. Measurements of base-line Rcoll for a given segment were reproducible (coefficient of variation 0.48). In contrast, we observed that the estimated dose of histamine required to increase Rcoll by 50% (ED150Rcoll) was extremely variable both among lung segments of an individual dog on a single experimental day (geometric mean variability of 40-fold) and for a given segment when reexamined on repeated occasions (geometric mean variability of 47-fold). The ED150Rcoll did not correlate with the base-line Rcoll. The degree of variability we observed suggests that peripheral contractile elements are under the influence of powerful local modulating factors that vary both regionally and temporally.

Maximal acid secretory response to histamine and its relation to parietal cell mass in the dog

1960 ◽  
Vol 199 (3) ◽  
pp. 579-588 ◽  
Author(s):  
I. N. Marks ◽  
S. A. Komarov ◽  
Harry Shay
Keyword(s):  
Dose Response ◽  
Acid Output ◽  
Cell Mass ◽  
Parietal Cells ◽  
Secretory Response ◽  
Response Curves ◽  
Entire Duration ◽  
The Mean ◽  
Dose Response Curves ◽  
Histamine Response

Gastric secretion in response to graded doses of histamine was obtained from the whole stomach in five trained dogs, and the animals were sacrificed to determine the total number of parietal cells in the stomach. Histamine was administered by single s.c. injection (Hsc) and continuous i.v. infusion (Hiv). Maximal histamine response (MHR) was determined, and studies permitting the construction of dose-response curves were carried out in three of the five dogs. Dose-response curves for acidity and for acid output and volume during the entire duration of secretory response to Hsc were also established. The MHR was found to be a linear function of both the total number of parietal cells ( P < .01) and the fundic mucosal volume ( P < .05). The magnitude of the MHR and the PCM in the five dogs was within the respective ranges reported in man, but the mean MHR per billion cells (9.8 ± 0.44 mEq/30 min.) and the mean MHR per 100 cc fundic mucosal volume (58.2 ± 5.12 mEq/30 min.) were both about 30% less than the respective ratios in man.

STUDIES ON THE PITUITARY MELANOPHORE-EXPANDING HORMONE WITH REFERENCE TO ITS IDENTITY WITH ACTH

1954 ◽  
Vol 11 (1) ◽  
pp. 7-13 ◽  
Author(s):  
B. KETTERER ◽  
ELIZABETH REMILTON
Keyword(s):  
Linear Regression ◽  
Dose Response ◽  
Progressive Increase ◽  
Regression Curve ◽  
Response Curves ◽  
Experimental Conditions ◽  
Response Data ◽  
The Mean ◽  
Dose Response Curves ◽  
Linear Regression Curve

SUMMARY 1. The standard Xenopus method for the assay of pituitary melanophore-expanding hormone has been critically examined, and the results from various assay procedures are statistically analysed. 2. Log dose-response data are well fitted by a linear regression curve. Responses at 3 hr give a steeper curve than those at 1½ hr. 3. Results collected 6 months apart show that the mean and slope of dose-response curves remain constant when Xenopus are given regular dosage; there is, however, a progressive increase of variance with time shown by the colony under these experimental conditions. 4. Evidence is presented to show that Xenopus must be minimally disturbed during assay, and that assay doses must be given not less than 1 day apart.

Thrombopoietin responsiveness reflects the number of doublings undergone by megakaryocyte progenitors

Blood ◽  
2004 ◽  
Vol 104 (8) ◽  
pp. 2291-2298 ◽  
Author(s):  
Jean-Michel Paulus ◽  
Najet Debili ◽  
Frédéric Larbret ◽  
Jack Levin ◽  
William Vainchenker
Keyword(s):  
Dose Response ◽  
Receptor Density ◽  
Response Curves ◽  
Age Model ◽  
Normal Human ◽  
The Mean ◽  
Dose Response Curves

Abstract To assess the variation of thrombopoietin (TPO) responsiveness associated with megakaryocyte (MK) progenitor amplification, TPO dose-response curves were obtained for normal human, single-cell plated CD34+CD41+ cells. The number of MKs per well was determined in situ and expressed as number of doublings (NbD). Dose-response curves of the mean frequency of clones of each size versus log TPO concentration showed highly significant differences in the TPO concentration needed for half-maximum generation of clones of different sizes (TPO50): 1.89 ± 0.51 pg/mL for 1 MK clones; 7.75 ± 0.81 pg/mL for 2 to 3 MK clones; 38.5 ± 5.04 pg/mL for 4 to 7 MK clones, and 91.8 ± 16.0 pg/mL for 8 to 15 MK clones. These results were consistent with a prediction of the generation-age model, because the number of previous doublings in vivo was inversely correlated with the number of residual doublings in vitro. TPO responsiveness decreased in vitro by a factor of 3.5 per doubling, reflecting the recruitment of progressively more ancestral progenitors. In support of this hypothesis, the more mature CD34+CD41+CD42+ cell fraction had a lower TPO50 (P &lt; .001), underwent fewer NbD (P &lt; .001), and expressed a 2.8-fold greater median Mpl receptor density (P &lt; .001) than the CD34+CD41+CD42– fraction. Progenitors that have completed their proliferative program have maximum factor responsiveness and are preferentially induced to terminal differentiation.

Dose-response Curves in the Fibrin Plate Assay Fibrinolytic Activity of Proteases

1974 ◽  
Vol 32 (02/03) ◽  
pp. 356-365 ◽  
Author(s):  
F Haverkate ◽  
D. W Traas
Keyword(s):  
Dose Response ◽  
Fibrinolytic Activity ◽  
Enzyme Concentration ◽  
Response Curves ◽  
Agar Gel ◽  
Porcine Tissue ◽  
Plate Assay ◽  
Fibrin Plate ◽  
Different Types ◽  
Dose Response Curves

SummaryIn the fibrin plate assay different types of relationships between the dose of applied proteolytic enzyme and the response have been previously reported. This study was undertaken to determine whether a generally valid relationship might exist.Trypsin, chymotrypsin, papain, the plasminogen activator urokinase and all of the microbial proteases investigated, including brinase gave a linear relationship between the logarithm of the enzyme concentration and the diameter of the circular lysed zone. A similar linearity of dose-response curves has frequently been found by investigators who used enzyme plate assays with substrates different from fibrin incorporated in an agar gel. Consequently, it seems that this linearity of dose-response curves is generally valid for the fibrin plate assay as well as for other enzyme plate bioassays.Both human plasmin and porcine tissue activator of plasminogen showed deviations from linearity of semi-logarithmic dose-response curves in the fibrin plate assay.

OVARIAN ASCORBIC ACID DEPLETION TEST FOR LUTEINIZING HORMONE

1967 ◽  
Vol 56 (4) ◽  
pp. 619-625 ◽  
Author(s):  
Hans Jacob Koed ◽  
Christian Hamburger
Keyword(s):  
Ascorbic Acid ◽  
Luteinizing Hormone ◽  
Dose Response ◽  
Response Curve ◽  
Dose Response Curve ◽  
Human Origin ◽  
Response Curves ◽  
Significant Difference ◽  
The Mean ◽  
Different Levels

ABSTRACT Comparison of the dose-response curves for LH of ovine origin (NIH-LH-S8) and of human origin (IRP-HMG-2) using the OAAD test showed a small, though statistically significant difference, the dose-response curve for LH of human origin being a little flatter. Two standard curves for ovine LH obtained with 14 months' interval, were parallel but at different levels of ovarian ascorbic acid. When the mean ascorbic acid depletions were calculated as percentages of the control levels, the two curves for NIH-LH-S8 were identical. The use of standards of human origin in the OAAD test for LH activity of human preparations is recommended.

BIOASSAY OF THYROID HORMONE USING HYPOTHYROID TADPOLES

1962 ◽  
Vol 41 (1) ◽  
pp. 143-153 ◽  
Author(s):  
U. Henriques
Keyword(s):  
Thyroid Hormone ◽  
Dose Response ◽  
Developmental Rate ◽  
Response Curves ◽  
Sodium Salts ◽  
Dose Response Curves

ABSTRACT A bioassay of thyroid hormone has been developed using Xenopus larvae made hypothyroid by the administration of thiourea. Only tadpoles of uniform developmental rate were used. Thiourea was given just before the metamorphotic climax in concentrations that produced neoteni in an early metamorphotic stage. During maintained thiourea neotoni, 1-thyroxine and 1-triiodothyronine were added as sodium salts to the water for three days and at the end of one week the stage of metamorphosis produced was determined. In this way identical dose-response curves were obtained for the two compounds. No qualitative differences between their effects were noted except that triiodothyronine seemed more toxic than thyroxine in equivalent doses. Triiodothyronine was found to be 7–12 times as active as thyroxine.

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