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. Results

Many papers have been written and figures givenshowing the late results of phrenicectomy with thepercentage " cured," improved, and so on. The

general opinion is that considerable benefit can beobtained in suitable cases. Yet there are a few likeGravesen 6 who consider " that the actual efficacyof the operation has been greatly exaggerated bymany," and that the indications are very limited.He finds that there were "only 27 cases (out of 153available for true statistical analysis ’) where wehave any right to say the patients were healed asthe result of the phrenic operation." Those figuresare, in my opinion (though not in Gravesen’s),most encouraging, because I would again emphasisethe fact that phrenicectomy must not be looked uponas a

" curative " measure, but as an auxiliary andancillary measure to other forms of treatment.For this reason I make no attempt to give figures

as to results. It is not possible to produce anythinglike an accurate statement. In some cases the

operation is done with a certainty of benefit to begained either as regards the disease or the relief ofsymptoms ; in others there is a reasonable possi-bility of benefit. In yet others a crush is indicatedas, while the result is doubtful, there is a possiblehope of success. In a disease like tuberculosis,with its disappointments and surprises, this successmust be sought for, at times even at long odds.

ComplicationsBerry 7 collected in 1930 the records of 4697

cases of phrenic nerve paralysis with a mortalityof 26 cases. Of the deaths 6 were due to bleedingfrom extraction of the nerve and 2 to a traumatic

emphysema and empyema associated with a trau-matic pneumothorax. These 8 cases were unquestion-ably accidents associated with evulsion of the nerve.Lung embolus and oedema accounted for 3 deaths,and dyspnoea and heart failure for another 3. Therewere 12 deaths from pneumonia and tuberculousdissemination. Of these 12, 5 were reported byLoewenthal8 who regarded the condition as an"

unspecifie, pneumonia " due to injury to the pleura

while evulsing the nerve. Another possible explana-tion is that during evulsion the dome gets drawnup into the thorax. At the moment that the nervefilaments give way the diaphragm returns with asudden, violent descent which may easily cause theaspiration into the lower lobe of secretion squeezedout into the bronchi during the period of elevation.Death from syncope has also been recorded at themoment of evulsion. It is phrenic evulsion not

phrenicectomy which is the operation which carriesthe immediate grave risks. I have seen 3 cases of

spontaneous, symptomless, partial pneumothoraxoccur within a week of evulsion.The most important of the later complications

are those due to the displacement of the stomachand duodenum and the dislocation of the cesophagealopening. Vomiting occurs very occasionally imme-diately after paralysis of the left dome, but usually

subsides in a day or two. Digestive disturbances,flatulence, and borborygmi may last somewhatlonger. It is rare for these even to be serious incharacter or of lasting duration. The most trouble-some complication in my series-and I am well onin my second thousand-has been the persistenceof borborygmi for eight months, when it rapidly dis-appeared. Digestive discomfort has been recordedafter paralysis of the right dome due to traction onthe first part of the duodenum.

Radiological examinations show, according to

Longuet and Launay, that with a high rise of theleft dome the stomach is elongated and shows a

large air space. Of more serious consequence is,however, the condition similar to that found witheventration of the diaphragm, a rotation, producinga partial volvulus of the stomach, causing a con-

striction across the length of the organ.Symptoms may therefore be produced by con-

striction of the oesophagus, of the stomach, or ofthe duodenum. In the majority of the cases the

symptoms are slight and transitory. Very rarelyonly are they of serious import, and they may thenbe associated with cardiac or pulmonary manifesta-tions, such as tachycardia or dyspnoea. Dyspnoeaof a mild grade may also be observed independentlyof the above complications. It may persist for twoor three weeks and then subside as compensationand adjustment take place.

REFERENCES

1. Patronikola, G. E.: Beitr. z. Klin. d. Tuberk., 1932, lxxxi., 600.2. Russell, A. W. : Tubercle, 1934, xv., 289.3. Nehil, L. W., and Alexander, J. : Jour. Thoracic Surg., 1933,

ii., 549.4. Matson, R. W. : Amer. Rev. Tuberc., 1930, xxii., 1.5. Lindberg, D. O. N. : Ibid., 1933, xxviii., 352.6. Gravesen, J. : Brit. Jour. Tuberc., 1934, xxix., 12.7. Berry, F. B. : Arch. of Surg., 1930, xxi., 1125.8. Loewenthal, M. : Beitr. z. Klin. d. Tuberk., 1929, lxxi., 712.9. Longuet, Y. J., and Launay, C.: Arch. méd.-chir. appar.

resp., 1934, ix., 157.

CARDIAC HYPERTROPHYIN EXPERIMENTAL NEPHRITIS

BY J. B. DUGUID, M.D. Aberd.PROFESSOR OF PATHOLOGY AND BACTERIOLOGY IN THE WELSH

NATIONAL SCHOOL OF MEDICINE, CARDIFF

THE occurrence of cardiac hypertrophy in the courseof an experimental nephritis which is tubular inorigin seems to open the way to some new conceptionsof the relationship between nephritis and vasculardisease.

Gough, Duguid, and Davies (1933) reported theproduction of a renal lesion in rats by the oral adminis-tration of large amounts of orthophosphates in con-junction with overdoses of vitamin D, and the lesionwas further described by me in 1934. It is a greatlyintensified form of the phosphate nephritis describedby Hirsch (1923), and by MacKay and Oliver (1930).Besides becoming chronic and progressive, and pro-ducing in some cases extreme disorganisation of thekidney, it has certain important features of interest.For example, although it is primarily and essentiallya tubular nephritis, it may in its more advancedstages develop glomerular, and even arterial changes,very similar to those found in man, and it may alsolead to a pronounced cardiac hypertrophy.The lesion can be readily produced in rats by feeding

them for 20-30 days on a diet of bread and potatoes,to which has been added acid sodium phosphate(5 parts per hundred, by weight), and at the same timeadministering a daily dose of 20,000-40,000 units ofvitamin D by mouth, in the form of calciferol. Atthe end of the period of treatment the rats may beput on a normal diet and allowed to recover. Theymay survive for many months, and most of themdevelop a chronic nephritis which tends to progressin severity, long after the treatment has been stopped.The primary lesion is a parenchymatous degenera-

tion, in which focal calcification of the tubules figuresprominently. This is followed by a gradual andprogressive destruction of entire tubules. Manyatrophy and disappear, whilst others dilate and becomecyst-like (Fig. 1). Large areas of shrinkage form in

422

the cortex, so that the kidney becomes extremelydistorted, with its surface pitted and granular. Inmost cases the glomeruli remain intact, but in a fewof the more severe ones, they undergo changes of anapparently toxic nature. These changes vary, butthey usually take the form of hyaline swelling of thecapillary membranes, and gradual hyaline trans-formation of the whole renal corpuscle, similar to thatseen in the so-called primary interstitial or primaryischaemic nephritis of man. The endothelial cells ofthe tufts gradually disappear. Later the wholestructure becomes fibrosed and obliterated. Whenthe glomeruli are affected, the arterioles may alsobe involved. Their walls become thickened andhyaline, and finally when the glomeruli are destroyed,the vessels also become obliterated. It should benoted that no direct relationship seems to existbetween the glomerular lesions and the tubular

degeneration in this nephritis. The glomeruli mayremain intact in the midst of extreme tubular destruc-tion, and when they do degenerate, the degenerationappears to be the result of some additional toxicfactlH, rather than of the tubular destruction itself.Nor is there any evidence that the glomerular degen-eration is the result of vascular disease. Suchvascular changes as arise invariably appear to be alater event, and seem therefore to be a result ratherthan a cause of the glomerular degeneration.

In some of the long-standing and severe cases,

changes may also be found in the arteries, especiallyin those parts where the parenchymatous shrinkageis most intense. Here the smaller interlobulararteries may appear narrow and tortuous, sometimesgiving the impression of hypertrophy, but without

FIG. 1.-Kidnep of a rat which survived 67 days after treatment.(x 50.)

any degenerative change in their walls. There seemsto be little doubt that this change represents a simplecontraction. The atrophy which occurs in thisdisease causes great shrinkage of the tissues, and thismust bring about a considerable reduction of the

capillary field. Some reduction of the arterialsupply is apparently called for, and the changeswhich occur in the arteries are probably to be regardedas something in the nature of a functional readjust-ment. One or two of the most long-standing cases

have shown some fibrous intimal thickening in addition,.but this is a comparatively rare finding.

It is only in the severe cases, which survive for two,or more months after the treatment, that cardiachVDertroDhvis found. Ittakes theform of con-c e n t r i c

thickening ofthe left tventriclevery similarto that seenin m a n.

Sometimesthe heart

FIG. 2.-The upper row of hearts are from.nephritic rats. Those below are fromnormal rats, each of the same body-weightas the corresponding one above.

increases tomore than double its normal weight. Fig. 2 shows-hearts of six of the most severe cases, compared withthose from normal rats of the same weight. In a

group of experiments recently carried out, 160 rats.were treated in the way specified above, and 98 ofthem survived the treatment for more than one month,the rest having died, or having been killed in the-early stages, for the purpose of investigating theinitial lesion. Of the survivors. 85 showed well-marked chronic lesions, and 23 of them were classi-fied as showing histologically ’intense nephritis,Fig. 1 showing a typical example. The hearts ofthese 23 cases were weighed after fixation in formalin.Expressed as percentage of the body-weight theyaveraged 6-7 with standard deviation 0-15, andextreme range from 0’46 to 1-06. The comparablerfigures from 60 normal rats were : average 0.43,,S.D. 0-09, and extreme range 0-26 to 0-66.These figures become even more striking when.

calculated in relation to the two-thirds power of thebody-weight (i.e., blood volume). For the 23 extremecases they read: average 3-89, S.D. 0-78, range2.57 to 521 ; and for the normals : average 2’18rS.D. 0-29, range 1-56 to 3-27.

In these 23 rats the amount of glomerular change was.variable-in some cases very inconspicuous---whilstwell-marked arterial changes were present in less thanhalf of them. Thus, although these figures showbeyond doubt that this experimental nephritis in rats.has effects on the heart similar to those seen in chronic

nephritis in man, they show no evidence that arterialdisease is concerned in the process. The cardiae

hypertrophy is clearly the result of the parenchy-matous destruction, and if an explanation on the linesof vascular disturbance has to be offered, the mostlikely one would seem to be that the disturbance ofrenal function produces toxic substances which affectthe heart through alterations in the blood pressure.

In man, cardiac hypertrophy is usually regardedas one of the consequences of the underlying arterialdisease from which the nephritis itself is supposed toarise. It thus forms part of the basis of the vasculartheory of nephritis. The findings in rats are of in-terest because they call for an entirely different inter-pretation. In view of them, the possibility of a

chronic nephritis with glomerular, arterial, andcardiac changes arising from a primary tubularnephritis has to be considered.

REFERENCES

Gough, J., Duguid, J. B., and Davies, D. R.: Brit. Jour. Exper.Path., 1933, xiv., 137.

Duguid, J. B. : Proc. Roy. Soc. Med., 1934, xxvii., 26.Hirsch, E. F.: Arch. Internal Med., 1923, xxxi., 862.MacKay, E., and Oliver, J.: Proc. Roy. Soc. Exp. Biol. and Med.,

1930, xxviii., 324.