TABLE III (Continued)
Case ‘%umber
Attack
Number
1irus isolation Need ralizing Antibod y Titer
, ‘
I rom tl SF From feces Virus. Acute Convalescent
6
?
Coxsackie B5
-NT.
ECHO25
Coxsackie B5
NT.
1 : 4 (12) 1 : 16 (19)
7 1
‘2
Coxsackie B5
Ni’.
-Polio III
Coxsackie B5
Polio III
1 : 16 (2) 1 : 64 (3)
1 : 64 (5) 1 : 64 (12)
8
2
NT.
Coxsackie B5
Coxsackie B5
Coxsackie B5
Coxsackie B5
Coxsackie B5
1 : <4 (7)
1 : 4 (3)
1 : <4 (32)
1 : 16 (10)
4)
. 2
Coxsackie B5
-NT. Coxsackie B5
N.T.
Coxsackie B5 1 : 16 (1) 1 : 16 (34)
10
2
NT.
-Coxsackie A9
CoxsackieB5
Coxsackie A9
CoxsackieB5
1 : 64 (5)
1:<4 (1)
1 : 64 (18) 1:<4 (8)
1 1
2
N.’!’. ECIIO6
Coxsackie B3
NT.
N.T.
NT.
NT. =not tested.
S Nummiber II) 1)slrellthleses iIl(hiCiItes (lays after Oliset of illness.
SUMMARY
Seventy-one patients with two or three
at-tacks of aseptic meningitis were seen during
the 16-year period, 1953-1968, when a total of
1,956 patients with that disease were observed.
All were under 15 years of age. The interval
between attacks ranged from a month to 4
years. Clinical and laboratory findings of
sequential attacks did not differ. Virological
data were available from both of two attacks
in 1 1 patients. These data indicate that a
per-son may be attacked with aseptic meningitis
more than once; usually the causative virus is
different in subsequent attacks.
TOORU NAKAO, M.D.
Roicm Miun, M.D.
Department of Pediatrics
Sapporo Medical College
s.1 W.16, Sapporo, Japan
REFERENCES
1. Klemola, E., and Lapinleumu, K. : Multiple
at-tacks of aseptic meningitis in the same
mdi-vidual. Brit. Med. J., 1: 1087, 1964.
2. Anderson, J. P. : Recurrent virus meningitis.
Brit. Med. J., 4:786, 1969.
3. Hinuma, Y., Murai, Y., Fukuda, M., Numazaki, Y., Ishida, N., and Nakao, T. : An outbreak of
aseptic meningitis associated with Coxsackie B5 and A9 viruses in northern Japan, 1961. Virological and serological studies. J. Hyg., 62:159, 1964.
4. Hinuma, Y., Uruno, K., Morita, M., Ishida, N., and Nakao, T. : Virological and epiderniologi-cal studies on an outbreak of aseptic meningi-tis caused by echovirus 4 in northern Japan in
1964. J. Hyg., 64:53, 1966.
5. Hinuma, Y., Murai, Y., and Nakao, T. : Two outbreaks of echovirus 14 infection : A possi-ble interference with oral poliovirus vaccine
and a possible association with aseptic
menin-gitis. J. Hyg., 63:277, 1965.
6. Nakao, T., Nitta, T., Miura, R., Ogata, K., Kume, T., Nobuta, K., and Hinuma, Y. : Clini-cal and epidemiological studies on an out-break of aseptic meningitis caused by Cox-sackie B5 and A9 viruses in Aomori in 1961. Tohoku J. Exp. Med., 83:94, 1964.
Hyperlipidemia
in the
Hemolytic-Uremic
Syndrome
Campbell and Carr#{233}’recorded the
occur-rence of hypertriglyceridemia in association
TABLE I
FASTING LIrID LEVELS IN TIlE PARENTS
OF Two OF THE PATIENTS
Case 1 Case 2
Data
-Father Mother Father Mother
Triglyceride
(mg/100 ml) 103 127 91 102
Cholesterol
(mg/100 ml) 173 208 207 229
Phospholipid
(mg/100 ml) 240 200 250 296
TABLE II
FASTING LIPID LEVELS IN 10 CONTROL SUBJECTS AGED 8 TO 24 MoN-ms
EXPERIENCE AND REASON-BRIEFLY RECORDED 777
of monozygotic twins and suggested that the
hypertriglyceridemia was present as an
in-herited disease.
The purpose of this paper is to describe the
finding of elevated triglyceride, cholesterol and
phospholipid levels in six children with
hemo-lytic-uremic syndrome.
MATERIALS AND METHODS
Serum triglyceride, cholesterol, and
phos-pholipid levels were measured in six out of
seven consecutive patients with
hemolytic-uremic syndome admitted to the Transvaal
Memorial Hospital for Children, Johannesburg.
The criteria for diagnosis were hemolytic
anemia with fragmentation of the red cells, a
platelet count below 140,000 per cmm, and
evidence of renal involvement.
Except where indicated, the serum lipid
levels were measured after a 12-hour fast.
Intravenous or oral fluids were not withheld during the fast and consisted of adequate fluid
and electrolytes, but no calories. During the
oliguric phase of the acute renal failure the
infants received a low-protein diet; the main
source of calories was glucose.
Fasting lipid levels of the parents of two of
the patients were measured after 12-hour fasts
(Table I) . The fasting serum lipid levels of 10
control subjects aged 8 to 24 months are shown in Table II.
Phospholipids were measured by the method
of Fiske and Subbarow,2 triglycerides by the
method of Van Handel and Zilversmit,3
modi-fled by Young and Eastman,4 and cholesterol
by the method of Sperry and Webb.5
CLINICAL FEATURES
The patients’ ages ranged from 6 to 13
months. There were five boys and one girl. All
the patients were of Caucasian origin. A history
of antecedent diarrhea was obtained in five
patients. The onset of diarrhea occurred from
2 to 12 days before the appearance of pallor.
On admission, all the babies were very pale,
four infants had purpuric spots, and all were
mildly to moderately edematous. During the
course of the illness all patients were oliguric or anuric for 1 to 7 days, all were hypertensive, and four of the infants had convulsions.
Cases IV, V, and VI underwent peritoneal dialysis. Heparin was administered to Cases I,
II, and III for periods of 5 to 11 days. Case
III also received prednisone in a dose of 3
mg/kg/day for 40 days. Reserpine and
di-hydralazine hydrochloride were administered
to two infants for varying periods.
RESULTS
The hemoglobin levels, platelet counts, blood urea, serum albumin, and lipid levels measured
in the six patients with a diagnosis of the
hemolytic-uremic syndrome are shown in Table
III. On admission, the hemoglobin levels
ranged from 3.4 to 8.4 gm/100 ml, the platelet
counts were from 18,000 to 70,000 per cmm,
and the blood urea levels were between 102
and 284 mg/100 ml. Fragmented red cells and
an elevated reticulocyte count were noted in
each patient.
Elevated triglyceride, cholesterol, and phos-pholipid levels were found in all six of the patients at some stage during the course of their disease.
Normal lipid values were found in the four
parents who were investigated (Table I).
Data Triglyceride Cholesterol Plzospholipid
Range
mg/100 ml 62-122 90-191 151-217
Mean
TABLE III
hemoglobin Platelets Blood Urea Serum Albumin Triglyceride Cholesterol
gm/iLk) ml (1,000’s) (mg/100 ml) (gm/100 ml) (mg/100 ml) (mg/1tX. ml)
CL.) 8.4 8.8 11.2 Case i)ays 1\umber oti adhIlissiOll 8 15 3.5 67
‘2 0,1 Inlnlissiohl
4
13
16
22
27
3 on 8(lIfliSSiOhL
17
29
36
49
4 oh adiiiissi#{248}mi
3
14
27
117
5 OIl 8(hlhliSsiOhl
8
19
33
77
6 ohi Il(lhhliSsiOhl
.5
17
23
40
62 102 3.00
120 55 3.18
160 35 3.00
700 47
-(;.8 18 172 2.90
- - 182 1.69
.5.0 115 148 1.74
8.2 - 164
-5.0 170 172
-8.5 140 180
-7.8 325 220
-44 284
-64 315
-32 91 2.70
263 117 2.21
20 150
-228 156 2.15
60 188 1.85
88 132 1.61
66 93
-53 120 1.98
100 52 2.03
970 26 3.25
- 28 3.23
70 252 2.90
208 45 1.84
345 19 2.85
240 34
-- 48
-Phospholipid (mg/100 ml) 220 350 175 248 133 182 136 190 168 255 339 392 672 466 594 387 544 476 513 436 450 286 360 170 282 170 280 208 -166 263 198 242 ‘218 -159 252 139 227 227 400 156 184 151 208 3.4 13.2 9.3 15.2 It) .4 3.0 4.5 4.4 11.0 8.7 9.4 9.4 5.3 9.1 8.5 10.0 11.6 906 290 136 103 225* 492 710 2520 1500 .550 373 1480 1460 655 390 810 572* .565 520 188 264 187 119 355* 211 288 240 197 312* 378 740 340 238
* Not Ufull 12-hour fast.
778 HEMOLYTIC-UREMIC SYNDROME
DISCUSSION
The finding of hypertriglyceridemia in six
patients with the hemolytic-uremic syndrome
together with normal serum triglyceride levels
in the four parents investigated, suggests that
an inherited process is unlikely. The lipids
reached their highest levels early in the disease.
In one patient, an initial decline of the lipid
levels was followed by an increase in the
tn-glyceride values coincident with a
recrudes-cence of the disease.
Bagdade, et al.
(
1968)
6 found a hypertri-glyceridemia in cases of nonnephrotic chronicrenal failure. Two possible mechanisms were
RESULTS OF LABORATORY INVmTIGATIONS
8.4 .50 187 3.09
7.8 60 124 1.86
9.4 318 109 3.04
8.5 270 124 3.38
131 214
158 211
276 358
201 242
EXPERIENCE AND REASON-BRIEFLY RECORDED 779
postulated: either, subnormal lipoprotein lipase activity or, depleted levels of tissue lipoprotein
lipase activity following prolonged heparin
ad-ministration. In the cases in the present report
the occurrence of hyperlipidemia was
inde-pendent of the administration of heparin.
The rise and fall in lipid levels was
inde-pendent of the serum albumin concentration
since both high and low levels were found with
similar serum albumin values (Table III).
There does not seem to be any correlation
be-tween the lipid levels and the hemoglobin, platelet, or urea levels.
Although the Shwartzman phenomenon has
never been proven to be the pathogenic
mech-anism for the development of the
hemolytic-iiremic syndrome, it has often been invoked as
such. It is thus of interest that Muller-Berg-haus, et al.
(
1964) found high cholesterol and Beta-lipoprotein levels during the generalizedShwartzman reaction in rabbits. It was their
opinion that elevated serum lipids might not
only directly accelerate intravascular coagula-tion but also blockade the phagocytic function of the reticuloendothelial system. Should these possibilities prove to be operative in the hemo-lytic uremic syndrome, therapeutic control of
the hvperlipidemia may well be indicated.
According to Frederickson
(
1968) , themechanisms for triglyceride removal are
un-certain. It is thought that the triglyceride is
hydrolyzed by lipase at the surface of capillary endothelial cells. A possible explanation for the hypertriglyceridemia in the hemolytic-uremic
syndrome may be decreased lipoprotein lipase
activity consequent upon widespread
destruc-tion of the endothelium of blood vessels in the kidney.
B. S. KAPLAN, MB., B. Cii., F.C.P. (S.A.),
Dn. PAED. (RAND). DIANA GALE, M.B., B.CII. Department of Pediatrics University of the Witwatersrand
TANIA IPP, MB., B.CH. School of Pathology
South African Institute for Medical Research University of the Witwatersrand
Johannesburg, South Africa
PRESENT ADDRESS: (B.S.K.) Renal
Labora-tory, Montreal Children’s Hospital, 2300 Tupper
Street, Montreal 108, Quebec, Canada.
\Ve thank Professor H. de v. Heese and Dr. R.
Drubin for permission to submit this paper for
publication; and Professor J. H. S. Gear, Professor
J. R. Murray, and Dr. I. Bersohn for facilities
pro-vided. Drs. J. Theron, J. Wolfsdorf, and C. M. Bakst allowed us to investigate their patients.
REFERENCES
1. Campbell, S., and Came, I. J.: Fatal
hemolytic-uraemic syndrome and idiopathic
livperlipi-daemia in monozygotic twins. Arch. Dis.
Child, 40:654, 1965.
2. Fiske, C. H., and Subbarow, Y. : The calori-metric determination of phosphorus. J. Biol. Chem., 68:375, 1925.
3. Van Handel, E., and Zilversmit, D. B. :
Micro-method for direct determination of serum tn-glycenides. J. Lab. Chin. Med., 50: 152, 1957. 4. Young, C., and Eastman, R. : A micromethod for
the determination of serum triglycerides. S. Afr. J. Lab. Clin. Med., 9:28, 1963.
5. Speny, W. M., and Webb, M. : Revision of
Schoenheimer-Sperry Method for cholesterol
determination. J. Biol. Chem., 187:97, 1950. 6. Bagdade, J. D., Porte, D. Jr., and Bierman,
E. L. : Hypertniglycenidaemia: A metabolic
consequence of chronic renal failure. New
Eng. J. Med., 279:181, 1968.
7. Muller-Berghaus, Von C., Huth, K., Krecke, H. J., and Lasche, H. C. : Blutlipide und
intra-vasale Geninnung in der Pathogenese des Sanarelli-Schwartzman-Phanomens. Schweiz. Med. Wschr., 94:1519, 1964.
8. Fredenickson, D. S. : Lipid metabolism :
Physio-logic. in Cooke, R. E., ed. Biologic Basis of
Pediatric Practice. New York: McGraw-lull,
p. 971, 1968.
Wilson-.Mikity
Syndrome
in
a
Full-Term
Male
Twin
In 1960 Wilson and Mikity’ reported a
syn-drome of chronic respiratory distress in prema-tune infants. Signs of hyperpnea, intercostal re-tractions, and cyanosis develop insidiously
dun-ing the first several weeks of life. Episodes of
apnea and rales on auscultation can occur.
Re-spiratory distress persists for the first month or two and slowly subsides in the infants who sur-vive. The chest radiographs show progressive
distinctive changes.2 During the acute phase,
the radiographs show a diffuse streaky
infil-trate, multiple small cyst-like foci, and often
hyperaeration. The intermediate stage is
