NationalLibraryOfScotland/medical-history-of-british-india huggingface dataset:
268
Anthelmintic Action of Phenothiazine
Summary of post-mortem findings :—
" Pulmonary embolism; thrombosis of termination of the abdominal
aorta ; occlusion of the large arteries of both hind limbs by thrombus and
mural thickening ; thrombosis and thickening of some veins in the hind limbs ;
numerous acute haemorrhagic erosions in fundus of stomach ; subendocardial
haemorrhage in left ventricle and right atrium ; congestion of lungs ; areas of
mucosal necrosis and ulceration in renal pelves and ureters, probably attri-
butable to the toxic action of the drug ; no oedema of the limbs.''
On subsequent page the authors say :—
" There was no evidence of verminous infestation in any of the vessels.
" The vascular lesions are definitely those of organized thrombosis and, in
the absence of cardiac disease and of arteritis due to Strongylus larvae, the
assumption of primary arterial disease of the vessels of the hind limbs seems
to be justified.
" Thrombosis of the veins in this horse was probably secondary to slowing
of the blood flow consequent upon the arterial obstruction.
" The arterial changes, because of their chronicity, cannot be attributed to
the action of phenothiazine, although the drug in the dose given may have been
toxic and may have precipitated the final illness."
PIGS
In the colons of two pigs received at the Institute, from a farm, nodules
resembling those produced by Oesophagostomum were found, although no worms
or larvae could be found in them.
Phenothiazine powder, derived from the breaking up of 1 gramme tablets,
was given to these pigs. They were all about three months old and their
average weight was 35 lb.
The pigs were divided into Groups A, B and C of ten pigs each and a
group of undosed controls.
The pigs in Group A were dosed and weighed
individually, each pig being given 0.5 gramme per lb. body weight of pheno-
thiazine. For the pigs in Groups B and C enough phenothiazine was weighed
out to give the pigs in Group B 0.2 gramme per lb. body weight and those in
Group C 0.1 gramme per lb. body weight. The total dose for each group was
then mixed in the trough with the food and the pigs were allowed to eat it,
the intention being to repeat the dose of 0.1 and 0.2 grammes per lb. body
weight if no ill effects were seen. The pigs took the doses well, but there was
no certainty that each pig got an equal amount of phenothiazine.
Group A, given 0.5 Gramme per lb. Body Weight, Dosed Individually.—
The day after the dose one pig of this group was brought to the Institute
unconscious and waving its legs in the air. It subsequently recovered by the
fourth day. Other pigs were similarly affected, but less seriously, showing
only drunken gait, inability to turn corners and weakness of the hind legs.
All of these subsequently recovered. The dosing was not repeated.
Group B, given 0.2 Gramme per lb. Body Weight as a Mass Dose in the
Feed.—The day after the dose one pig only showed some slight weakness in the
hind legs. A second dose of 0. 2 gramme per lb. body weight was given on the
GEOFFREY LAPAGE 269
second day. On the third day six pigs showed complete loss of co-ordination,
but recovered by the fourth day. The dose was not repeated after this second
dose.
Group C given 0.1 Gramme per lb. Body Weight as a Mass Dose in Feed.—
After the first dose no pigs showed any symptoms and on the second day a
second dose of 0.1 gramme per lb. body weight was given. The day after this
second dose three or four pigs showed slight rolling gait and inco-ordination,
but all recovered. The dosing was not repeated, so that these pigs had had two
doses on successive days of 0.1 gramme per lb. body weight, 0.2 gramme per
lb. in all.
Two months later it was adjudged that all the pigs which had had pheno¬
thiazine were in better condition than those which had not. The weight
increase, however, was roughly the same in the dosed groups and in the undosed
controls.
The impression gained from this inconclusive experiment was that the
method of dosing was responsible for the ill-effects observed. Only a few of
the pigs were adversely affected, which suggested that these obtained more
food and therefore more than their allotted dose of phenothiazine. This the
writer had expected, but it was thought worth while to see if this method of
dosing was safe in practice. The following additional experiment suggests
that an overdose of the drug obtained in this way was probably the correct
explanation of the ill-effects.
Twenty-seven pigs about three months old, undergoing a metabolism ex-
periment at this Institute, with an average weight of 42 lb., were each given
individually 0.1 gramme per lb. body weight of the 5 gramme tablets of pheno-
thiazine now being made by Imperial Chemical Industries. The pigs were
starved for 24 hours before the dose was given. They were being fed indivi-
dually so that they could be dosed individually by mixing the dose with the
feed.
None of the pigs showed any visible ill-effects. None showed any inco-
ordination. The exact weighings of each of the ingredients of the rations that
were being given to them indicated that the food intake of some of the pigs
was reduced after the drug was given, although no visible effects on the animals
could be noted. After five days all the pigs had resumed their normal intake
of food. There is as yet no clear proof that this reduction in food intake was
due to the phenothiazine.
Two other pigs of the same lot as the above 27 and the same age were also
dosed individually as follows :—
One weighing 61 lb. was given 0.1 gramme per lb. body weight of pheno-
thiazine tablets and showed no visible ill-effects. Four days later, when its
urine was no longer red, it was given 0.5 gramme per lb. body weight without
visible ill-effects.
The other, weighing 37 lb. was given 0.14 gramme per lb. body weight
without visible ill-effects and four days later it was given 0.2 gramme per lb.
body weight without visible ill-effect.
These observations, inconclusive as they are, do indicate that pigs three
months old dosed individually with 0.1 gramme phenothiazine per lb. body
weight do not suffer any visible ill-effect, When the dose for a number of pigs
GEOFFREY LAPAGE 271
(4) A similar marked fall in the egg count of a single goat from 3,650
e.p.g. to 150 e.p.g. was noted 24 hours after it had been given, without toxic
effect, a dose of 0.15 gramme per lb. body weight of phenothiazine.
(5) Attempts to kill the ciliates in the rumen of a sheep by introducing
phenothiazine powder into the rumen through a fistula did not kill any appre-
ciable number of the ciliates. Thionol appeared in the urine of the sheep
5½ hours after phenothiazine was set free in the rumen.
(6) Doses of 80 to 125 grammes of phenothiazine did not produce any visi-
ble toxic effect in calves six months old.
(7) The passage of red urine and bronzing of the mucosae, which usually
persists for four days or so after the administration of phenothiazine, was noted
in all the sheep, horses and calves treated. When the doses were larger, loss
of appetite and listlessness were noted. These are signs that the dose should
not be increased, nor repeated until a considerable interval has elapsed.
(8) Phenothiazine powder at the rate of about 0.1 gramme per lb. body
weight administered to horses, either mixed in a feed of bran and treacle or
given suspended in water with a stomach pump, reduced the strongyle egg
count to 0, or near that figure, and the egg count did not rise again appreciably
for many weeks, although the horses were at grass.
(9) One horse, given 500 grammes of phenothiazine in water with a
stomach pump (a dose of about 0.5 gramme per lb. body weight) suffered little
more than transient loss of appetite and listlessness. After the same dose 49
days later the same horse became restless and uncomfortable and refused to
feed for a few days, but subsequently recovered. Another horse, given 1,000
grammes with a stomach pump showed marked toxic effects, but the existence
in this animal of thrombo-angiitis rendered it impossible to say whether the
symptoms were due to this disease or to the phenothiazine. Examination of
the blood of these horses showed no other abnormality than a transient excess
of methaemoglobin.
(10) Evidence is given which suggests that phenothiazine should be admi-
nistered to young pigs with great care, although doses of 0.5 gramme per lb.
body weight appear to have no toxic effects on mature pigs.
HIGH RECORDS CONTRASTED WITH UNSELECTED
RECORDS AND WITH AVERAGE RECORDS AS A
BASIS FOR SELECTING COWS*
BY
J. C. BERRY AND J. L. LUSH
Iowa Agricultural Experiment Station
(Reprinted from the Journal of Dairy Science, Vol. 22, No. 8, August-1939)
W HILE making some preliminary studies of suitable ways to test the rela-
tive values of production records, singly and in various combinations, for
predicting future records of the same cow and for evaluating her transmitting
ability, we noted an article by Copeland (2) purporting to show some advan-
tages for using a cow's highest record as an index to her lifetime producing
ability and to her transmitting ability. As our data, which came from a
different source, seemed appropriate for testing Copeland's conclusions, we
repeated a part of his analysis on our own material and added a few other
features which, it is hoped, will demonstrate why the ex post facto selection
of the highest record is an unsound procedure—a procedure more likely to
lead to fallacious results than if an unselected record or, better still, the
average of all a cow's records were used as the measure of her ability.
A major difficulty associated with the use of the highest record in com-
paring cows (and not mentioned by Copeland) is that in practice most com-
parisons will need to be made between cows which have not completed an
equal number of recorded lactations at the time the comparisons must be
made and which, therefore, have not had the same number of chances to
make a high record. The obvious unfairness so introduced seems of so much
practical importance that we will refer to it again in some detail after first
presenting our findings on a basis comparable with Copeland's.
DATA STUDIED
We studied the records of 115 Holstein cows, each of which had completed
at least six Herd Improvement Registery lactations and had one or more
daughters each of which had completed at least two records 1 . All records
were brought to a mature ' B ' basis by use of the conversion factors listed
in the Holstein Red Books.
FINDINGS
The first step was to compare the correlations between various records and
averages. These are shown in Table 1 along with the corresponding ones
*Journal Paper No. J-626 of the Iowa Agricultural Experiment Station, Ames, Iowa.
1 These data were those included in some originally assembled for another purpose—
that of proving sires. Here a 6-record cow was used as many times as she had tested
daughters. Actually there were 89 different cows. If the dam of a 6-record cow had
two or more records, that dam was treated as a daughter. The relation is a parent-
offspring one in either case. The findings should be practically the same as if there had
actually been 115 different 6-record cows, each with one tested daughter.
( 272 )
J. C. BERRY AND J. L. LUSH 273
reported by Copeland. For the four ' repeatability ' comparisons (the first
four in Table 1), our coefficients are lower than those reported by most studens
of this question, while those of Copeland are among the highest we have
ever seen. More typical are findings like those of Plum (5) that a
correlation of .60 existed between records of the same cow in the whole popu
lation of records from many herds, but that on an intra-herd basis the
correlation between records of the same cow was reduced to .40. Perhaps a
high degree of heterogeneity from herd to herd existed in Copeland's data.
TABLE I
Correlation coefficients for Holstein H. I. R. records Jersey R. of M. records and
Jersey Herd Test records
Variates correlated
First record with the second . . . .
Second record with the third . . . .
Third record with the fourth . . . .
Fourth record with the fifth . . . .
First with ave. of next four . . . .
First with ave. of all five . . . .
Highest with ave. of all five . . . .
Highest with ave. of other four . . . .
Lowest with ave. of all five . . . .
Lowest with ave. of other four . . . .
Coefficients of correlation
115
Holstein
H.I.R.
cows
.30
.42
.55
.45
.49
.68
.90
.83
.79
.70
197
R of M.
cows*
.71
.77
.69
.59
.62
.75
.92
. .
. .
. .
166
Jersey
.78
.80
.75
.83
.80
.88
.92
. .
. .
. .
*Copeland's data.
If the various records were all equally correlated (r) with each other, the
correlation between the first and the average of the next four would be ex
pected to be r √4/1+3r. It is a little lower than this (if for r is used the
simple arithmetic average of the four repeatability correlations shown) in
all three sets of data (especially so in the Jersey R. of M. records), thus
indicating that the correlations between non-consecutive records (not shown)
average somewhat lower than those between consecutive records. Similarly,
if all the correlations between the individual records were equal to r, the
correlation between the first record and the average of the first five records
would equal √+4r/5. Again the actual figures are lower (much lower in
the case of the Jersey R. of M. records) than they would be if the non-con
secutive correlations averaged as high as the consecutive ones which are
shown.
274
A Basis for Selecting Cows
The numerical values to be expected in the case of the correlation between
the highest record and the averge of all five are not clear because of the com-
plex statistical relations brought about by the ex post facto selection of the
highest record. That such selection has an effect on the correlation subse-
quently calculated can be made clear by considering an extreme case in which
it is assumed that we have samples of five records each from cows between
which there really are no intrinsic differences, the variation between the
various records being wholly due to varying external circumstances and to
sampling variations. This is the same statistical problem as would exist in
FIG. 1. The statistical consequences of the ex post facto selection of the highest
record among five. The normal curves, all drawn at the same height on the ordinate axis,
illustrate the variation to be expected between different records of the same cow in a
population of cows which all have exactly the same real ability. In such a population it
would sometimes happen that the highest of five records would be very high ; sometimes
it would be moderately high ; and sometimes even the highest record would be moderately
low. When a sample of five records is located along the abscissa according to the highest
record in it, the other four must come from the unshaded portions of the frequency curves
—i.e. from below the line RS. When the highest record is large, it can be considerably
larger than the average of the other four records ; but when the highest record is itself
rather low, it cannot be very different from the average of the other four. This gives rise
to a high correlation between the high and the average of the others, to curvilinear regres-
sion, and to a funnel-shaped distribution.
studying random samples of five records each, drawn from the same universe.
Since all of the other four records must be lower than the high record, it
follows that the samples in which the high record itself has a low value will
be samples in which all five records happened to come from the lower part
of the frequency curve. But in such cases the other four will rarely be much
below the high one and the two variates will be closely correlated.
PLATE XX ]
[ Ind. J. Vet. Sci. & Anim. Husb., Vol. XI, Part IV
OUTKRAAL IN THE FOREST AREA AT MUKTESWAR
FIG. 1.
FIG. 2.
J. C. BERRY AND J. L. LUSH 275
Figure 1 is intended to show graphically what would happen in such a
case if the highest of the five records in each sample were correlated with the
average of the other four. Six normal curves with their means at the same
level have been drawn at intervals of 100 lb. along the abscissa to show the
restrictive effect of locating the sample along the abscissa according to the
highest of the five records in it. In each case the other four records must
all be below the diagonal RS, and must come from the unshaded portions of
the normal curves. At the right hand side of the graph (where the high
record happens to be very high) little restriction is laid on the magnitude of
the other four records, but toward the left hand side most of the unshaded
portion of the curve lies very near the diagonal RS and the average of the
other four records cannot be far below the high record.
Because of the constricting influence of the high record on the magnitude
of the other four, the total distribution becomes funnel shaped and the line
BCD (drawn through the means of the unshaded portions of the six normal
curves) showing the regression of the average of the other four on the high
one is curvilinear in character. The extreme narrowing of the distribution
when the high record itself is not very large, is particularly potent in giving
a large correlation between the high record in the sample and the average of
FIG. 2. Correlation (. 83) between the highest record and the average of the other
four records in a population of 115 H. I. R. cows. All points must fall below the diagonal
AB. The regression line is the best-fitting straight line but does not tell the full story,
since the real relation between the two variates is curvilinear. The restrictive influence of
the highest record on the magnitude of the other four records is especially evident towards
the left side of the diagram.
the other four records, even in an extreme case like this where the samples
come from the same universe (as from a group of cows all with the same pro
ducing ability).
276
A Basis for Selecting Cows
Actually, of course, there are differences between the cows, too, and this
gives the regression line more of an upward slope and somewhat less curvi¬
linearity although the funnel shape of the data and the extreme restriction
at the left are conspicuous features of the actual data as shown in Figure 2.
It is thus apparent that the correlation coefficient for the high record and
the average of the other four owes a part of its magnitude merely to the fact
that the first mentioned variate was selected because it was the high record.
Because of the curvilinearity and the funnel shape, the biometric relations
seem complex and we do not know how to separate the observed correlation
coefficient into the spurious part which comes from this useless ex post facto
arrangement of the data and the part which would show the genuine useful-
ness of the high record in predicting records not yet made when the high one
was selected.
When the highest record is correlated with an average of the five which
include it, the coefficient becomes still larger. The situation is the same as
shown in Figure 2 except that each point is now moved upward one-fifth of
the distance which in Figure 2 separates it from the line AB. Naturally
those lying farthest away are moved most and so the correlation is distinctly
increased but no new knowledge is gained.
Figure 3 shows the first record as correlated with the average of the other
FIG. 3. Correlation (.49) between the first record and the average of the next four
records. Same cows as in Figure 2. The straight line shows the linear regression of the
average of the other four records on the first record.
four. Using the first record sets no restriction on the magnitude of the
average of the other four. The other four can all be below the first, or all
above it, or some on one side and some on the other. Such a correlation in an
unbiased estimate of the usefulness of the first record for predicting the
average of the other four.
278
A Basis for Selecting Cows
first three were compared with the fourth and with the fifth; and then the
unselected first, second and third were correlated also with the fourth and
fifth records. The results of such a fair test on our data are shown in Table
II. The differences between the correlations in the same column are not sta-
tistically significant (on this amount of data—probably the question should
TABLE II
Correlation coefficients between a cow's first three records (selected and unselected)
and her later records
The six variates correlated with the fourth and fifth records
Highest of first three
.
.
.
.
.
.
.
Lowest of first three
.
.
.
.
.
.
.
Medium of first three
.
.
.
.
.
.
.
First record
.
.
.
.
.
.
.
Second record
.
.
.
.
.
.
.
Third record
.
.
.
.
.
.
.
Correlation coeffi-
cients with
Fourth
record
.61
.56
.57
.39
.56
.55
Fifth
record
.29
.45
.31
.39
.24
.26
be investigated on more extensive data), but the contrast with the figures in
Table I shows clearly that much of the apparent superiority of the high
record (and of the low) in that table was due to the spurious effects of the
method of its choice.
PREDICTION OF DAUGHTER'S RECORDS
Table III shows the correlations of the average of the first two records of
the daughters with the high and low of all five records, with the high, low
and medium of the first three, and with the five unselected single records.
For comparison, Copeland's coefficients are included in this table. All the
coefficients are below .34. The considerable differences between some of them
do not seem to fit any particular pattern and are not statistically significant on
this amount of data. So far as these data go, any one of these records is
about as useful as any other for predicting the production of daughters.
USE OF AVERAGES
Averages of all available records are theoretically more useful than single
records in evaluating the differences between cows. The authors are at
present studying, on a larger amount of data, the question of whether records
actually do behave in this way. Some of the preliminary results are pre-
sented in Tables IV and V.
J. C. BERRY AND J. L. LUSH 279
TABLE III
Correlation coefficients between the average of the first two daughter records and
various records of the dam
Dam's record which was correlated with the average of the
daughter's first two records
Highest of all five records
.
.
.
.
.
.
Lowest of all five records.
.
.
.
.
.
.
Highest of first three records
.
.
.
.
.
.
Lowest of first three records
.
.
.
.
.
.
Medium of first three records
.
.
.
.
.
.
First record
.
.
.
.
.
.
Second record
.
.
.
.
.
.
Third record
.
.
.
.
.
.
Fourth record
.
.
.
.
.
.
Fifth record
.
.
.
.
.
.
Copeland's comparissons
Highest records of 176 dams and highest records of the daughters
Average records of 176 dams and average yield of their tested
daughters
.
.
.
.
.
.
Correlation coeffi-
cients
.29
.15
.24
.19
.33
.24
.14
.23
.29
.13
.29
.30
TABLE IV
Correlations of averages of a cow's first records with her subsequent records and with
her daughter's records
Dam's average
Ave. of first two records .
Ave. of first three records .
Ave. of first four records .
Ave. of all five records . .
Correlations coefficients
Dam's
fourth record
Actual
.59
.65
. .
. .
Exp.
.47
.51
. .
. .
Dam's
fifth record
Actual
.38
.38
.44
. .
Exp.
.47
.51
.53
. .
Daughter's
ave. of first two
Actual
.24
.27
.30
.29
Exp.
.25
.27
.29—
.29 +