A reversible concentrating defect in predominantly unilateral renal Hodgkin's disease

CASE REPORTS

A Reversible Concentrating Defect in Predominantly Unilateral Renal Hodgkin’s Disease:%

THOMAS

H. STEELE,

CARY A. PRESANT, ARTHUR

M.D.7

A. SERPICK,

Baltimore,

The function of each kidney was assessed separately in a patient with pre-

M.D.t

dominantly unilateral renal involvement by Hodgkin’s disease. Initially, the greatly enlarged diseased kidney exhibited diminished concentrating

M.D.

abil-

ity, and its glomerular filtration rate was only 6 per cent of the contralateral

Maryland

value. After a three month course of cytotoxic chemotherapy,

utilizing a

combination of four drugs, the size of the affected kidney decreased substantially. Although the glomerular filtration rates on both sides remained unchanged, concentrating

ability improved markedly on the diseased side.

In addition, the relative rates of uric acid and potassium excretion normalized, as compared to the contralateral

kidney. These data imply that the

renal concentrating mechanism in disease may be affected by intrarenal parameters extrinsic to the remaining functioning nephrons, possibly by such potentially reversible factors as cellular infiltrate, edema and elevated renal interstitial pressure. Defective tional

urinary

hallmarks

concentration of chronic

has long been held to be one of the func-

renal disease [l].

Abnormalities

trating mechanism are said to occur especially chronic parenchymal infection [2-41. However, chronic

pyelonephritis

[5-71,

and in experimental

chronic renal disease [8,9], the concentrating diseased kidney usually has been comparable lateral

organ.

Those studies

suggested

of the concen-

early during the course of in patients with unilateral animals

with

unilateral

ability of nephrons within the to that of the normal contra-

that the inability

to produce

a con-

centrated urine, as noted in patients with chronic renal insufficiency, may not arise as a result of intrinsic disease within residual functioning nephrons but, instead, may be a byproduct of an adaptive process occurring when a few nephrons are forced to meet the total needs of the organism [7,10-121. In contrast,

Stamey

and Pfau [13]

have reported

a case of unilateral

chronic pyelonephritis in which the concentrating ability of the diseased kidney was markedly diminished. More recently, Ronald et al. 1141 investigated a series of patients the

* From

the

Cancer Baltimore, should 3100 21211.

be

Park

Manuscript of

$ Present of

48,

to Drive, received

address:

The

Medicine,

Wyman

Dr.

The

Medicine,

St.

1970

Baltimore Park

Requests

for

Arthur June

Barnes Louis,

Serpick, Maryland

24,

University

Drive,

reprints

A.

Baltimore,

Chicago,

address:

March

Institute,

3100

21211.

addressed

Wyman

Department

Volume

Cancer

Center,

Maryland

t Present

partment

National

Research

1969. of

Chicago,

Illinois. Hospital, Missouri.

De-

maximum

urine

with unilateral

osmolality

on the

renal bacteriuria bacteriuric

and found that

side was significantly

lower than that on the contralateral side. Furthermore, the maximum urine osmolality of patients with renal bacteriuria increased following antimicrobial therapy. However, the pathophysiologic significance of diminished urinary concentrating ability is unclear, since the extent to which intrarenal factors, extrinsic to nephrons per se, may affect the concentrating process has not been determined. In this communication we report functional data from individual kidneys in a patient who initially presented with massive involvement of one kidney by infiltrative Hodgkin’s disease and manifested an ipsilateral concentrating defect. After combination chemotherapy the neoplastic infiltrate in the affected kidney regressed markedly and the parameters of urinary concentration, as well as the pattern of solute excretion on that side, reverted toward normal. 375

REVERSIBLE

CASE

CONCENTRATING

DEFECT IN RENAL

HODGKIN’S

DISEA SE

REPORT

-

STEELE

The patient cause

year old white

had Hodgkin’s disease node biopsy specimen

man (B.W.)

was known

to have

since 1963 when a peripheral lymph was obtained after the discovery of

asymptomatrc cervical and mediastinal lymphadenopathy. He was treated with regional radiation in 1963 and 1964. Hepatomegaly was noted in 1965, and abdominal lymphangiography showed retroperitoneal node involvement. Subsequently he was treated with chlorambucil, nitrogen mustard and corticosteroids at various times. After the appearance of refractory fever in February 1968, Baltimore Cancer Research Center.

he was referred

to the

On physical examination, the blood pressure was 100/60 mm Hg. Apart from mild pitting edema of the lower extremities and an enlarged right inguinal lymph node, significant abnormalities were confined to the right side of the abdomen. The liver edge was palpable 2 cm below the right costal margin, but a larger mass occupied both right abdominal quadrants. This mass was firm, nontender and moved with respiration. No abdominal bruits were heard. Laboratory data included a hemoglobin of 9.2 gm per 100 ml and a white blood cell count of 15,500 per cu mm. A bone marrow aspirate revealed increased numbers of eosinophils and mononuclear cells. Urinalyses were unremarkable, as were the serum urea nitrogen and creatinine determinations. Total serum proteins measured 6.2 gm per 100 ml, with an albumin of 2.5 and gamma globulin of 1.0 gm per 100 ml. The serum ceruloplasmin was 75 mg per 100 ml (normal range, 20 to 35 mg per 100 ml). The alkaline phosphatase was 19 King-Armstrong units. The etythrocyte sedimentation rate was 64 mm per hour. A liver scan demonstrated patchy uptake of ~!‘“Au. Abdominal venography disclosed no evidence of venous obstruction but did reveal caval displacement by a mass in the right abdominal quadrants. During intravenous infusion pyelography and the venous phase of arteriography, the right kidney showed only minimal opacification and measured 25 cm in length whereas the left kidney measured 17 cm (Fig. 1). The pyelocalyceal system was visible only on the left. Subsequently, retrograde urography of the right kidney showed anterolateral displacement of the ureter, but the calyces were not dilated. On retrograde femoral arteriography, the right renal vascular pattern was not characteristic of a renal carcinoma; there were no obstructing arterial lesions. In May 1968 the patient underwent divided renal function studies, to be described. Because of uncertainty regarding the renal lesion, an open biopsy of the right kidney was also performed. On microscopic examination, there was a marked increase in interstitial tissue, composed of fibrous and cellular elements including eosinophils, lymphocytes and reticulum cells, as well as Reed-Sternberg cells (Fig. 2). Small numbers of both obsolescent and morphologically normal glomeruli were present, and the amount of tubular tissue was strikingly diminished. The over-all histologic appearance suggested replacement and destruction of renal tissue by an infiltrative interstitial neoplastic disease process. The patient’s course continued to be febrile with temperatures up to 102°F. Extensive search for an infectious etiology was unrewarding. Subsequently, the patient was treated with a regimen of three courses of combination chemotherapy [15]. Each course was begun at an interval of four weeks and consisted of vincristine, 2.5 mg, and nitrogen mustard, 11 mg, both given intravenously once weekly for two weeks. Concurrently, prednisone, 75 mg, and procarbazine, 175 mg, were administered orally each day for the two week period. After the first course the prednisone dosage was tapered and administration of the drug discontinued. 376

was maintained

of fibrotic

detected A twenty-elght

ET AL

culous

changes

on antituberculous in the upper

on roentgenographic disease

could

therapy

be-

lobe of the right

lung

examination,

not be documented.

(PAS) and streptomycin reaction to isoniazid. After three months

were

used

of therapy

although

because the

tuber-

Aminosalicylic

acid

of an untoward

patient’s

temperature

was consistently normal. The enlarged inguinal node had decreased in size and the liver was only barely palpable under the costal margin, with more homogeneous uptake of isotope on a repeat liver scan. The right kidney measured 15 cm in length, and the ureter and collecting system could be visualized on infusion pyelography (Fig. 3). The left kidney measured 15.5 cm. The serum alkaline phosphatase and sedimentation rate had become normal, and the ceruloplasmin level had fallen to 24 mg per 100 ml. In September 1968 the patient again underwent divided renal function studies, performed in the same manner as previously. Subsequently, he has been able to resume his duties as a policeman and has received further chemotherapy intermittently. The size of his kidney has remained stable.

METHODS-RENAL

FUNCTION

STUDIES

Prior to both studies the patient received a regular diet with a normal protein content. Food and medications were withheld for twelve and twenty-four hours, respectively. Only the right ureter was catheterized; spinal anesthesia was used during the first study and topical anesthesia during the second. Urine from the right kidney was collected from the ureteral catheter, whereas that from the left kidney was collected from an urethral catheter placed in the bladder after cystoscopy. The bladder was emptied by suprapubic pressure and air instillation terminally. Follow-up urine cultures after each study failed to reveal significant bacteriuria. Venous blood specimens were drawn into heparinized syringes from an indwelling needle, prior to the administration of inulin and p-aminohippurate (PAH), and at the mid-point of each clearance period. After the administration of priming doses of inulin and PAH, a sustaining infusion was begun at a rate of 5 ml per minute, utilizing an infusion pump. In addition to inulin and PAH, the sustaining infusion also contained 270 mEq sodium chloride, 40 gm urea and 1 unit Pitressi& per L of solution. After forty minutes of equilibration, clearance periods ranging from fourteen to seventeen minutes commenced, and specimens for three clearance periods were obtained. Plasma PAH concentrations did not exceed 1.7 mg per 100 ml. During the first study, after specimens were obtained at low PAH levels, the plasma PAH concentrations were raised to values between 35 and 38 mg per 100 ml, and specimens for three additional periods were obtained for the determination of maximum PAH secretion rate (Tmp.,rl). lnulin was measured by a semi-automated modification of a resorcinol method [16]. PAH was determined by the procedure of Harvey and Brothers [17], inorganic phosphate by a modification of the method of Kraml [18], and uric acid by an automated enzymatic spectrophotometric method [19]. Urine and plasma osmolalities were measured with an osmometer, for the estimation of osmotically “free” water reabsorption (TrFTl,). Sodium and potassium were determined on a flame photometer with a lithium internal standard. Standard clearance calculations were employed. The mean values are entered in Tables I through III.

RESULTS During

both

estimated less

for

studies by the

the

large

the

glomerular

clearance right

of

kidney The

filtration

inulin, than

was the

American

rate 94

smaller Journal

(GFR),

per left of

cent kid-

Medicine

REVERSIBLE

CONCENTRATING

DEFECT

Fig.

3.

An

Fig.

1.

A roentgenographic for

lowing

aortography.

failed

to

visibly

measured

Fig.

2.

prior

The and

therapy. by

48,

a

right

Left. neoplastic

March

1970

of note

of

during

the

interstitial

size 25

renal

replacement infiltrate,

cm

medium.

nephrogram

right

prior

nephrographic

measured

contrast

a good

the

renal

the

kidney the

provided

Photomicrographs to

comparison disease,

concentrate

17 cm

nephrons

Volume

Hodgkin’s

to

chemo-

phase in

The

length left

foland

kidney

creased During trast mained

RENAL

infusion

combination therapy

IN

HODGKIN’S

pyelogram

chemotherapy. 10

cm

this medium at

whereas

repeat

visibly,

only

5 per

obtained

The that

examination even cent

DISEASE

length

of

the

left

the

right

though

its

of the

value

-

STEELE

following of

the

had

courses

kidney

diminished

kidney

had

only

concentrated

glomerular in the

three

right

ET

1.5 the

filtration

left

rate

AL.

of decm. conre-

kidney.

effect.

biopsy

specimen

and including

taken

destruction

of

fibrous

and

pleomorphic power 1,000).

view

cellular of

a

elements

Reed-Sternberg

(magnification cell

is also

X shown

100).

Right,

(magnification

high X

REVERSIBLE

CONCENTRATING

DEFECT

IN

RENAL

HODGKIN’S

DISEASE

ney (Table I). Although GFR on the left ranged between 84 and 91 ml per minute, it was only 4.4 to 5.2 ml per minute on the right. PAH clearances (C,,,,,) and filtration fractions (FF) did not change significantly during the time interval encompassing chemotherapy for Hodgkin’s disease (Table I). During the first study, performed under a maximum antidiuretic stimulus, fractional water excretion (V:GFR) of the greatly diseased right kidney was more than double that on the left. The osmolality of urine from the right kidney was only slightly greater than that of plasma (Tables I and II), but that from the left was more than twice the plasma osmolality. T“ZI,,,:GFR, while essentially zero on the right, was 2.1 ml per 100 ml GFR on the left. Concurrently, however, relative solute excretion (C,,,,,,:GFR) differed between the two kidneys by only 30 per cent. Although fractional sodium excretion ([UV:F]Na) by the right kidney was greater, the actual values, 2.9 per cent of the filtered sodium excreted on the right and 2.1 per cent on the left, were comparable. Likewise, the fractions of filtered phosphate excreted ([UV: Flphos) agreed bilaterally within 16 per cent. However, relative excretion rates of potassium and urate differed for the two sides. Potassium excretion per unit GFR (U,V:GFR) of the right kidney was more than double that of the left. The urate to inulin clearance ratio (C,,,:GFR) was far greater on the right (Table I) and, in somewhat parallel fashion, Tm,..,I, :GFR was 63.4 mg per 100 ml GFR for the right kidney, as opposed to 48.2 mg per 100 ml GFR for the left. After chemotherapy, the size of the right kidney had decreased markedly, but GFR and C,,,, had changed little, with values on the right continuing to be approximately 5 per cent of those on the left. However, V:GFR on the right side had decreased to a value only 25 per cent greater than that on the left and the osmolality of urine from the right kidney was 524 mOsm per kg, a value 75 per cent greater than the simultaneous plasma value (Tables I and II). This compared favorably to the urine osmolality of 628 mOsm per kg from the left kidney. Likewise, T”ll,r,:GFR on the right was 2.4 ml per 100 ml, a value greater than that of the contralateral kidney during the first study. During the second study, T%:GFR on the right was 74 per cent of the value on the left, in contrast to the very low previous value (Fig. 4). During the second study, fractional sodium and phosphate excretion values remained similar bilaterally. However, although U,V:GFR of the right kidney had formerly exceeded that of the left, relative potassium excretion was comparable on both sides (Table I). Likewise, C,,,:GFR nearly equalized bilaterally (Fig. 4). Plasma potassium was slightly less during the second study (Table II). Although U,V:GFR of the left kidney was more than double the earlier value, U,V:GFR of the right kidney had not changed significantly, remaining at nearly 80 yEq per 100 GFR. During the second study, the plasma urate value was more than twice the value observed initially (Table II). This probably reflects allopurinol therapy prior to the first study and its cessation after clinical improvement. Before chemotherapy, urine concentrations of potassium and urate were nearly identical bilaterally, although V:GFR was far greater on the right (Table Ill). In con378

-

STEELE

ET

AL.

Ii

The American

Journal of Medicine

REVERSIBLE

TABLE

Mean Solute Concentrations

II

Total Solute* (mDsm/kg)

Study

DEFECT

IN

(m &IL)

(m Z/L)

(mg/lOO ml)

3.1

3.3

34

3.1

7.1

r During urea infusion.

each

kidney,

potassium, nearly

as

and an

then

equal

for

right

kidney.

of the

right

kidney

48,

March

both

after

index

the

inorganic

eased

Volume

comparison

before

is taken

of

the

functional

chemotherapy.

of

the

If

functioning

excretion

rates

per

phosphate

and

urate

organs

In addition, increased

1970

AL.

Uric Acid

Inorganic Phosphorus (mg/lOO ml)

may be in error due to an indeterminate amount of leakage around the solitary right ureteral catheter. The extent of agreement of the values of GFR, for each side, on two separate occasions, does militate somewhat against the possibility of a significant leak. A modest amount of leakage would not invalidate the principal conclusions of this study, since all the parameters in Table I, except GFR, C,,, and V, would be unaffected in measurements of right-sided function. Large contributions of urine from the right kidney to bladder specimens would have tended to minimize apparent functional differences between kidneys. However, urine concentrations of sodium and inorganic phosphate were far greater on the left side during the first study (Table Ill). The diminished concentrating ability of the right kidney during the first study was probably not a result of altered solute excretion, since C,,,:GFR was only 30 per cent greater on that side. Likewise, filtration fractions agreed within 10 per cent, although the intrarenal distribution of blood flow might have differed bilaterally. The concentrating abnormality appears to correlate with diminished over-all volume reduction of glomerular filtrate on the right side, since V:GFR was more than twice as great on that side, even though V was still less than 5 per cent of GFR. During the first study, the fractional excretion values of both sodium and phosphate did not differ greatly between the two sides; whereas the excretion rates of potassium and urate, relative to GFR, were far greater on the right. Since urine concentrations of potassium and uric acid were essentially equal for the two sides, similar over-all concentration gradients for each of these two substances, between tubular fluid and plasma, were maintained by both kidneys. Tm,.,,:GFR was 32 per cent greater on the right. Some degree of flow dependence of PAH secretion has been demonstrated in perfused segments of the rat nephron [25]. In addition, radioactive PAH injected intratubularly has been shown to exchange rapidly with PAH in the extracellular space [26]. Since some degree of flow dependence, for both potassium

III

Data

kidneys

ET

Ureat Nitrogen (mg/lOO ml) 30

TABLE

(Cl,,)

STEELE

3.5

Since there is no reason to suspect that the mean GFR per nephron of either kidney changed significantly during the time interval encompassed by these studies, the number of functioning nephrons presumably remained approximately constant. The length of the large right kidney decreased 10 cm during therapy, whereas that of the smaller left kidney decreased only 1.5 cm. Thus, both organs were apparently involved by Hodgkin’s disease, but the degree of infiltration of the right was far greater. Although renal lymphoma is usually an asymptomatic process, often diagnosed roentgenographically and causing little apparent disturbance in kidney function [20221, renal involvement by Hodgkin’s disease or reticulum cell sarcoma has occasionally been sufficiently severe to cause acute renal failure [23,24]. If involvement similar to that of the right kidney had occurred bilaterally in our patient, advanced renal insufficiency would have resulted. The values of urine flow and GFR reported in Table I

two

-

4.1

COMMENTS

Diagrammatic

DISEASE

141

trast, the urine concentrations of sodium and inorganic phosphate were far less on the right than on the left, thus nearly compensating for the disparity in V:GFR. During the repeat study, after V:GFR on the right had decreased, the concentrations of potassium and urate in the urine again were similar bilaterally. The patterns of potassium and urate excretion appeared to reflect the extent of reabsorption of tubular fluid, whereas those of sodium and inorganic phosphate did not. The disparities between the two kidneys in the relative excretion rates of potassium and urate, as well as urinary concentrating ability, had essentially disappeared (Fig. 4).

4.

HODGKIN’S

138

* Plasma osmolality.

Fig.

RENAL

in Plasma

289 299

I II

CONCENTRATING

following the during

urine

patterns

the

inulin

nephron nephron

shrinkage osmolality

Pitressinm

of

tended

to of

clearance

water,

of

(mE:/L) Study

Right kidney Left kidney

86 142

Right kidney Left kidney

159 179

Inorganic Phosphorus (mg/lOO ml)

17 16

Uric

’ (mg;Z

ml)

I 4.6 13

22 21

15 17

19 23

sodium,

become

(Uosm)

(mF:/L)

the

population

the

infusion.

of

Mean Urinary Solute Concentrations

greatly and

Study II

more disTc,,~

24 25

379

REVERSIBLE

CONCENTRATING

DEFECT

IN

RENAL

HODGKIN’S

DISEASE

[27,28] and urate [29] excretion, has been demonstrated at very low rates of urine flow, one could speculate that the discrepancies in potassium and urate excretion durrng the first study were related in large part to the difference in V:GFR between the two sides. The excretion of these two substances, predominantly through tubular secretion under normal circumstances, was enhanced when the over-all degree of tubular fluid reabsorption by the right kidney was diminished. In contrast, the settings of over-all glomerular-tubular balance for sodium and phosphate, substances generally considered to participate in a filtration-reabsorption type of excretion mechanism, were approximately the same bilaterally. There was no roentgenographic evidence of vascular obstruction, either arterial or venous, to explain the initial disparity in V:GFR. Acute urinary outflow obstruction during right ureteral catheterization seems unlikely; although the urine sodium concentration was less on the right during the first study, the elevated V:GFR on that side contrasts to the usual finding during acute obstruction [30]. There was no evidence of outflow obstruction on retrograde urography, but intrarenal obstruction to outflow, possibly on the basis of neoplastic infiltrate or increased interstitial tissue pressure, could have occurred. In chronic partial obstruction, although V:GFR is elevated, sodium excretion rates are usually increased [30.33]. However, the right kidney never exhibited a marked sodium-losing tendency, although its fractional sodium excretion values were somewhat higher. Diminished proximal sodium reabsorption, with subsequent augmentation of its distal delivery and exchange for potassium, might have occurred; but, then C,.,:GFR probably would have paralleled V:GFR. The collecting ducts might have been relatively impermeable to water as a consequence of neoplastic infiltration, resulting in insufficient osmotic equilibration between collecting duct fluid and the hyperosmotic medullary interstitium during antidiuresis. Some degree of equilibration did occur, for urine from the right kidney was invariably hyperosmolal to plasma. There was no histologic evidence of selective neoplastic involvement of periductal or medullary regions. Intrinsic disease of nephrons of the right kidney, either affecting sodium reabsorption in the ascending limb of the loop of Henle or the renal response to antidiuretic hormone, seems unlikely. However, if functional deficiencies within nephrons had been responsible for the concentrating defect, the abnormalities must have been corrected by chemotherapy. Likewise, unknown toxic substances liberated by neoplastic cells, with an effect on renal sodium transport or antidiuretic hormone action, have not been identified. The most striking feature during the patient’s response to therapy was the regression in size of the right kidney. Concurrently, its concentrating ability improved, and the patterns of renal solute excretion tended to equalize bilaterally. Likewise, the over-all extent of tubular fluid reabsorption by the right kidney was enhanced. Since the functioning nephron population presumably remained unchanged, the very marked decrease in size of the organ probably reflected diminished interstitial neoplastic infiltrate and possibly edema. Conceivably, an alteration of the renal interstitium, either through a diminished compartmental volume or a decrease in interstitial pressure, could have created a more favorable environment 380

-

STEELE

ET

AL

for medullary solute conservation by the countercurrent mechanism. With closer proximity of residual juxtamedullary nephrons, the same amount of solute might have been reabsorbed into a smaller Interstitial volume -a condition presumably more conducive to the development and maintenance of elevated medullary solute concentrations [34,35]. Enhanced medullar!/ osmolallty would have promoted additional reabsorption of tubular fluid during its passage along the descending limb of the loop of Henle prior to its arrival in the distal tubule [36]. In turn, this might have contributed to normalization of the pattern of any flow-dependent solute excretion by the right kidney, especially for substances excreted primarily through distal tubular secretion. In recent years, an hypothesis has been enunciated describing nephron function in stable chronic renal insufficiency in terms of the appropriately altered function of a relatively few residual nephrons [7,10-121. There is no reason to expect that nephrons within a kidney affected by Hodgkin’s disease would conform to the functional pattern exhibited by nephrons within the chronically diseased kidney, even though urine osmolality and intravenous urographic visualization improved after partial reversal of the disease process [37,38]. However, the present case might be viewed as a fortuitous instance in which an exaggerated therapeutic response to the treatment of predominantly interstitial renal involvement could be obtained. In patients with unilateral chronic pyelonephritis [57], urine osmolality and TC~d,:GFR of the diseased kidney have usually been somewhat less than for the contralateral organ. However, the overwhelming impression has been one of functional homogeneity of nephrons on the two sides-both with respect to the concentrating process and the excretion of other solutes [39]. In contrast, a patient of Stamey and Pfau [13] exhibited markedly diminished concentrating ability on the affected side, and the data of Ronald et al. [14] imply that maximum urine osmolality is reduced ipsilaterally, early in the course of unilateral renal parenchymal infection. The discrepancies between these studies probably reflect not only differences in methodology but also in the degree and duration of disease as well. One might speculate that in most of the recorded series the patients have had advanced unilateral disease because of the large differences in GFR usually observed between the two sides [5-71. However, GFR was reduced only 35 per cent in the infected kidney of Stamey’s patient, and histologic examination showed a dense interstitial inflammatory response [13]. The unilaterally bacteriuric patients with ipsilateral concentrating defects described by Ronald presumably had early stages of parenchymal involvement, probably with destruction of only limited numbers of nephrons [14]. Although the extent of morphologic change within their kidneys is unknown, reversible inflammatory cell infiltrates and edema in the medullary interstitium might have contributed to their reversible concentrating deficits. Thus, if the present case is considered in terms of the successful amelioration of predominantly interstitial renal disease, with an approximately constant nephron population, these data may be useful in resolving some of the apparent discrepancies in concentrating ability observed in unilateral chronic pyelonephritis in man. The

American

Journal

of Medicine

REVERSIBLE

CONCENTRATING

ACKNOWLEDGMENT We would

biopsy

like to express

Sutherland,

who

DEFECT

provided

our appreciation invaluable

aid

to Dr. John

C.

in interpreting

the

IN

RENAL

material.

Norman

HODGKIN’S

DISEASE

In addition,

Zimmerman

Dr. James

performed

for the first and second

-

the

studies,

STEELE

ET

Calhoun

ureteral

AL.

and

Dr.

catheterization

respectively.

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