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EFFECT OF THYROXINE ON BACTERIAL GROWTH IN VITRO
716
pheral lymphocyte immunoglobulin surface-markers revealed 3’r T cells and 2’!r, B cells. The remaining 95% of the lymphocytes were unmarked "null" cells (performed by Ms Yehudit Stup of the Hebrew University Medical School). The patient subsequently did not relpond satisfactorily to combined chlorambucil-prednisone therapy and died
MALIGNANCY IN CHRONIC RENAL FAILURE SIR,--Dr Matas and his colleagues’ reported an increased incidence of malignancy in the 646 dialysis and transplant patients treated in their department since 1963, both during progressive urxmia and after transplantation. We wish to report that two of the eleven patients admitted thusfar to the Shaare Zedek Hospital dialysis unit have developed fatal malignancies of an unusual nature.
about
a
year and
a
half after clinical
onset
of the disease with
over-
whelming sepsis probably due to bowel perforation. These cases seem unique. Squamous-cell carcinoma was prein only 3% of the 2861 cases of bladder cancer reviewed by Sarma2and none has been reported in dialysis or transplant patients. Since the tumour was found three years after bsmodialysis was begun, it is unlikely that it was present before the patient was uraemic. The two-year survival after the diagnosis of stage-iv cancer suggests that patients with such growths be treated with urinary diversion procedures and/or dialysis, as the likelihood of distant metastases and early death is less than in transitional-cell carcinoma of the bladder.2 The lack of response of the patient with leukaemia to chemotherapy was discouraging. Treatment had been started only after anaemia, a rapidly rising white-blood-cell count and progressive hepatosplenomegaly developed. The meaning of the "null" cell finding is unknown, but it may presage disease resistant to chemotherapy.
sent
CASF 1.--After 39 months of bi-weekly hsemodialysis using the ’Travenol RSP’ machine, a 46-year-old man with chronic pyelonephritis complained of urgency and pelvic pressure. Cystoscopy and cystourethrography (fig. 1) revealed a bladder tumour. On cystostomy an
Department of Surgery, Radiology and Pathology Institutes, Shaare Zedek Hospital, Jerusalem, Israel. Renal Unit,
BARAUCH J. HURWICH ALEXANDER CHAIT MARCEL DOLLBERG LEAH DOLLBERG
EFFECT OF THYROXINE ON BACTERIAL GROWTH IN VITRO
SIR,-I have used 0-01% solution of thyroxine sodium at pH
Fig. I.-Cast
1: appearance
on
7.4 as a growth stimulant for Escherichia coli. Before inoculation 1 ml of thyroxine solution was layered on the surface of nutrient agar plate and the same amount was added to 9 ml nutrient broth. One loopful of a 2h growth of E.coli in nutrient broth was used for inoculation of both thyroxine treated and control agar plates. The same amount of inoculum was also added to thyroxine treated and control broth tubes containing 10 ml of medium. After incubation for overnight at 37°C, the growth on the thyroxine-treated agar medium was luxuriant and the col-
cystourethrography.
E. coli colonies in control
Fig. 2.--Case 1: bladder.
microscopic
appearance of
invasive, stage tv, inoperable cancer was discovered. Histologically, it fulfilled the criteria for squamous-cell carcinoma of the bladder in that there was keratinisation and no transitional-cell epithelium (fig. 2). No special therapy was attempted. For 18 months the patient functioned normally. He died 23 months after diagnosis in a cachetic state with signs of local invasion but no distant metastases. CASt 2.---A 48-year-old woman developed chronic lymphatic leukxmia three years after beginning on haemodialysis for chronic renal failure of undetermined xtiology. Immunoglobulin levels were low. Peri1. Matas, A
J.,
Simmons,
R. L.,
Kjellstrand,
Wajarian, J. S. Lancet, 1975,i, 883.
(left)
and
thyroxine-treated (right) media,
squamous-cell carcinoma of
C. M., Buselmeier, T.
onies were more confluent. Colony diameters were about twice the size of those on the control plate (see figure), and the .urbidity was eight times that of the control one, when compared in a photoelectric colorimeter using an uninoculated nutrient broth medium as a blank. The morphological characteristic and staining reaction of the organisms were the same as those of organisms grownm the control media, and the biochemical properties, antibiotic sensitivity, and serological reactions were also similar. There is no alteration of animal pathogenecity with the hormonetreated organisms.
J., 2
Sarma, K P. Int. Surg. 1970, 53, 313.
717
simple technique warrants a slo«-groveing aerobic organisms such This
trial in the culture of M. tuberculosis and
as
.tf.M. Department of Pathology and Bacteriology, B.
treated with 14 days of pentamidine isothionate (4 mg/kg), and then a short course of sulphadiazine and pyrimethamine. He made an uneventful recovery. Renal function was unaffected.
P. carinii infections have a reputation of being discovered all often at necropsy. The outcome of this case illustrates that this need not be so if clinicians responsible for the care of immunosuppressed patients maintain a high index of suspicion.
too
S. Medical College,
S. K. BISWAS.
Bankura, West Bengal, India.
We thank Mr H. a
VENTRICULAR FIBRILLATION AFTER NARCOTIC WITHDRAWAL
Department of Nephrology, Southmead Hospital,
firmed that she had taken an unknown quantity of diamorphme by subcutaneous injection some 12 hours previously. At endotracheal intubation mucopus was found in the hypopharynx. She was ventilated with high-concentration oxygen and nalorphine 10 mg was administered slowly intravenously (naloxone was not readily available). This resulted in pupillary dilatation and improvement in her respiratory effort, with clearing of central cyanosis. Some 10 minutes later, however, ventricular fibrillation occurred. Defibrillation was necessary on two occasions, and after the second time extreme sinus bradycardia 10 beats per minute) was evident. Isoprenaline 2 mg t.v., administered as a bolus injection, resulted in persistent supraventricular tachycardia. Progressively severe bronchospasm developed in association with hypotension and a right-ventricular strain pattern on the electrocardiogram. Pupillary constriction, 30 min after ventricular fibrillation, responded to naloxone 0.4 mg t.v., but respiration did not improve. Chest X-ray showed bilateral patchy consolidation. Hypercapnia and metabolic acidosis were present. Treatment with ampicillin and hydrocortisone was started, but 45 minutes later the blood-gases had deteriorated further, and intermittent positive-pressure respiration became necessary. This clinical picture was compatible with the so-called adult respiratory-distress syndrome previously described in diamorphme overdose and inhalational pneumonia.2 Atter 14 hours of artificial ventilation the patient was extubated and spontaneous respiration readily established, with mild bronchospasm persisting for a few days. case
shows
a
hazard of the
use
of the narcotic
us to
publish details
of
DAVID KNIGHT
Bristol BS10 5NB.
SIR.—The dangers of the use of the narcotic antagonist, naloxone, have been emphasised.l We should like to draw attention to a case of ventricular fibrillation following the use of a narcotic antagonist. A 21-year-old woman presented at the casualty department with typical signs of severe opiate poisoning-deep coma, flaccidity with pin-point pupils, and severely depressed respiration. Later, she con-
This
J. 0. White for allowing
patient under his care. DAVID PUGSLEY
ALPHA-FETOPROTEIN IN URINE OF HEPATOMA PATIENTS
SIR,-Although the presence of a-fetoprotein (A.F.P.) has been reported in human fetal urinel2 and the urine of rats with chemically induced hepatoma,3 we could find no such record for the presence of A.F.P. in the urine of hepatoma patients. Recently we had the opportunity of examining 20 urine samples from 9 patients with clinically confirmed hepatoma and found significant amounts of A.F.P. in the majority of these samples. A.F.P. analyses were performed by counterimmunoelectrophoresis (sensitivity: 200 ng/ml) and radioimmunoassay using pure A.F.P. labelled with 125I, and a monospecific antibody to the purified A.F.P. (sensitivity: 5 ng/ml). Our results are shown in the accompanying table. OCCURRENCE OF A.F.P. IN URINE OF PATIENTS WITH HEPATOCELLULAR CARCINOMA
anta-
gonist, nalorphine. Narcotic withdrawal may have precipitated ventricular fibrillation. Such a reaction might also occur with the otherwise "safe" narcotic antagonist, naloxone. We would emphasise the need for full resuscitation facilities when such agents are used in severe narcotic poisoning. Department of Materia Medica and Department of Anæsthetics, Stobhill General Hospital, Glasgow, G21 3UW.
R. LAWRENCE F. R. LEE
J.
EARLY DIAGNOSIS OF PNEUMOCYSTIS CARINII INFECTION
* with
SIR,—The letter by Dr Yates and others (Sept. 27, p. 610) the need for clinical awareness of carinii in susceptible patients. Rapid infections Pneumocystis diagnosis is one of the few factors influencing the outcome.’ prompts
us to
emphasise
A 36-year-old man, who had received a renal allograft 2tyears previously was admitted complaining of 3 weeks’ increasing breathlessnes’) and non-productive cough, night sweats, and weight-loss, which had not responded to conventional antimicrobial therapy. He had been n good health and was on a constant dose of prednisolone (7.5 mg/d) and azothiaprine (125 mg/d). Physical examination revealed only , tachypnœa, and fever. Chest X-ray showed patchy shadowof both bases. The clinical diagnosis of P. carinii pneumonia was confirmed bv identification of the organism in one of the specimens a bronchial brush biopsy done on the day of admission. He was S. C. Br. med. J. 1975, iii, 434. Robin E. D. , et al. New Engl. J. Med. 1973, 288, 292. 1. Walzer, P. D., Perl D. P., Krogstad, D. J., Rawson, P. G., Schultz, Ann intern Med 1974, 80, 83.
2.
It will be noted that there seems to be no relationship between the albumin and A.F.P. content of urine inasmuch as, in a given patient, samples of urine containing either 370 or 3600 ng/ml A.F.P. show approximately 30 mg/dl albumin, and conversely, in another patient, urines with either 30 or 300 mg/dl albumin contain 90-120 ng/ml A.F.P. However, there does seem to be a relationship between blood level and urinary level of A.F.P. as manifested in Ma. (blood 640 000 ng/ml, urine 1500 ng/ml), Mu. (blood 350 000 ng/ml, urine 300-3600 ng/ml) and Bu. (blood 54-104 000 ng/ml urine 110-165 ng/ml), but not in patients Kam. and Be. Purves. has also noted the presence of A.F.P. in urine of hepatoma patients 1. 2. 3.
1. Allen
M
G.,
’Labstix’, Ames Company, Elkhart, Indiana, U.S.A.
Gitlin, D. Boesman, M. J. clin. Invest. 1966, 45, 1826. Linder, E., Seppälä, M. Acta path. microbiol. scand. 1968, 73, 565. Okon, E., Rosenmann, T., Dishon, T., Boss, J. H. Br. J. Cancer, 1973, 27, 362.
4. Purves, L. R. Personal communication.
pheral lymphocyte immunoglobulin surface-markers revealed 3’r T cells and 2’!r, B cells. The remaining 95% of the lymphocytes were unmarked "null" cells (performed by Ms Yehudit Stup of the Hebrew University Medical School). The patient subsequently did not relpond satisfactorily to combined chlorambucil-prednisone therapy and died
MALIGNANCY IN CHRONIC RENAL FAILURE SIR,--Dr Matas and his colleagues’ reported an increased incidence of malignancy in the 646 dialysis and transplant patients treated in their department since 1963, both during progressive urxmia and after transplantation. We wish to report that two of the eleven patients admitted thusfar to the Shaare Zedek Hospital dialysis unit have developed fatal malignancies of an unusual nature.
about
a
year and
a
half after clinical
onset
of the disease with
over-
whelming sepsis probably due to bowel perforation. These cases seem unique. Squamous-cell carcinoma was prein only 3% of the 2861 cases of bladder cancer reviewed by Sarma2and none has been reported in dialysis or transplant patients. Since the tumour was found three years after bsmodialysis was begun, it is unlikely that it was present before the patient was uraemic. The two-year survival after the diagnosis of stage-iv cancer suggests that patients with such growths be treated with urinary diversion procedures and/or dialysis, as the likelihood of distant metastases and early death is less than in transitional-cell carcinoma of the bladder.2 The lack of response of the patient with leukaemia to chemotherapy was discouraging. Treatment had been started only after anaemia, a rapidly rising white-blood-cell count and progressive hepatosplenomegaly developed. The meaning of the "null" cell finding is unknown, but it may presage disease resistant to chemotherapy.
sent
CASF 1.--After 39 months of bi-weekly hsemodialysis using the ’Travenol RSP’ machine, a 46-year-old man with chronic pyelonephritis complained of urgency and pelvic pressure. Cystoscopy and cystourethrography (fig. 1) revealed a bladder tumour. On cystostomy an
Department of Surgery, Radiology and Pathology Institutes, Shaare Zedek Hospital, Jerusalem, Israel. Renal Unit,
BARAUCH J. HURWICH ALEXANDER CHAIT MARCEL DOLLBERG LEAH DOLLBERG
EFFECT OF THYROXINE ON BACTERIAL GROWTH IN VITRO
SIR,-I have used 0-01% solution of thyroxine sodium at pH
Fig. I.-Cast
1: appearance
on
7.4 as a growth stimulant for Escherichia coli. Before inoculation 1 ml of thyroxine solution was layered on the surface of nutrient agar plate and the same amount was added to 9 ml nutrient broth. One loopful of a 2h growth of E.coli in nutrient broth was used for inoculation of both thyroxine treated and control agar plates. The same amount of inoculum was also added to thyroxine treated and control broth tubes containing 10 ml of medium. After incubation for overnight at 37°C, the growth on the thyroxine-treated agar medium was luxuriant and the col-
cystourethrography.
E. coli colonies in control
Fig. 2.--Case 1: bladder.
microscopic
appearance of
invasive, stage tv, inoperable cancer was discovered. Histologically, it fulfilled the criteria for squamous-cell carcinoma of the bladder in that there was keratinisation and no transitional-cell epithelium (fig. 2). No special therapy was attempted. For 18 months the patient functioned normally. He died 23 months after diagnosis in a cachetic state with signs of local invasion but no distant metastases. CASt 2.---A 48-year-old woman developed chronic lymphatic leukxmia three years after beginning on haemodialysis for chronic renal failure of undetermined xtiology. Immunoglobulin levels were low. Peri1. Matas, A
J.,
Simmons,
R. L.,
Kjellstrand,
Wajarian, J. S. Lancet, 1975,i, 883.
(left)
and
thyroxine-treated (right) media,
squamous-cell carcinoma of
C. M., Buselmeier, T.
onies were more confluent. Colony diameters were about twice the size of those on the control plate (see figure), and the .urbidity was eight times that of the control one, when compared in a photoelectric colorimeter using an uninoculated nutrient broth medium as a blank. The morphological characteristic and staining reaction of the organisms were the same as those of organisms grownm the control media, and the biochemical properties, antibiotic sensitivity, and serological reactions were also similar. There is no alteration of animal pathogenecity with the hormonetreated organisms.
J., 2
Sarma, K P. Int. Surg. 1970, 53, 313.
717
simple technique warrants a slo«-groveing aerobic organisms such This
trial in the culture of M. tuberculosis and
as
.tf.M. Department of Pathology and Bacteriology, B.
treated with 14 days of pentamidine isothionate (4 mg/kg), and then a short course of sulphadiazine and pyrimethamine. He made an uneventful recovery. Renal function was unaffected.
P. carinii infections have a reputation of being discovered all often at necropsy. The outcome of this case illustrates that this need not be so if clinicians responsible for the care of immunosuppressed patients maintain a high index of suspicion.
too
S. Medical College,
S. K. BISWAS.
Bankura, West Bengal, India.
We thank Mr H. a
VENTRICULAR FIBRILLATION AFTER NARCOTIC WITHDRAWAL
Department of Nephrology, Southmead Hospital,
firmed that she had taken an unknown quantity of diamorphme by subcutaneous injection some 12 hours previously. At endotracheal intubation mucopus was found in the hypopharynx. She was ventilated with high-concentration oxygen and nalorphine 10 mg was administered slowly intravenously (naloxone was not readily available). This resulted in pupillary dilatation and improvement in her respiratory effort, with clearing of central cyanosis. Some 10 minutes later, however, ventricular fibrillation occurred. Defibrillation was necessary on two occasions, and after the second time extreme sinus bradycardia 10 beats per minute) was evident. Isoprenaline 2 mg t.v., administered as a bolus injection, resulted in persistent supraventricular tachycardia. Progressively severe bronchospasm developed in association with hypotension and a right-ventricular strain pattern on the electrocardiogram. Pupillary constriction, 30 min after ventricular fibrillation, responded to naloxone 0.4 mg t.v., but respiration did not improve. Chest X-ray showed bilateral patchy consolidation. Hypercapnia and metabolic acidosis were present. Treatment with ampicillin and hydrocortisone was started, but 45 minutes later the blood-gases had deteriorated further, and intermittent positive-pressure respiration became necessary. This clinical picture was compatible with the so-called adult respiratory-distress syndrome previously described in diamorphme overdose and inhalational pneumonia.2 Atter 14 hours of artificial ventilation the patient was extubated and spontaneous respiration readily established, with mild bronchospasm persisting for a few days. case
shows
a
hazard of the
use
of the narcotic
us to
publish details
of
DAVID KNIGHT
Bristol BS10 5NB.
SIR.—The dangers of the use of the narcotic antagonist, naloxone, have been emphasised.l We should like to draw attention to a case of ventricular fibrillation following the use of a narcotic antagonist. A 21-year-old woman presented at the casualty department with typical signs of severe opiate poisoning-deep coma, flaccidity with pin-point pupils, and severely depressed respiration. Later, she con-
This
J. 0. White for allowing
patient under his care. DAVID PUGSLEY
ALPHA-FETOPROTEIN IN URINE OF HEPATOMA PATIENTS
SIR,-Although the presence of a-fetoprotein (A.F.P.) has been reported in human fetal urinel2 and the urine of rats with chemically induced hepatoma,3 we could find no such record for the presence of A.F.P. in the urine of hepatoma patients. Recently we had the opportunity of examining 20 urine samples from 9 patients with clinically confirmed hepatoma and found significant amounts of A.F.P. in the majority of these samples. A.F.P. analyses were performed by counterimmunoelectrophoresis (sensitivity: 200 ng/ml) and radioimmunoassay using pure A.F.P. labelled with 125I, and a monospecific antibody to the purified A.F.P. (sensitivity: 5 ng/ml). Our results are shown in the accompanying table. OCCURRENCE OF A.F.P. IN URINE OF PATIENTS WITH HEPATOCELLULAR CARCINOMA
anta-
gonist, nalorphine. Narcotic withdrawal may have precipitated ventricular fibrillation. Such a reaction might also occur with the otherwise "safe" narcotic antagonist, naloxone. We would emphasise the need for full resuscitation facilities when such agents are used in severe narcotic poisoning. Department of Materia Medica and Department of Anæsthetics, Stobhill General Hospital, Glasgow, G21 3UW.
R. LAWRENCE F. R. LEE
J.
EARLY DIAGNOSIS OF PNEUMOCYSTIS CARINII INFECTION
* with
SIR,—The letter by Dr Yates and others (Sept. 27, p. 610) the need for clinical awareness of carinii in susceptible patients. Rapid infections Pneumocystis diagnosis is one of the few factors influencing the outcome.’ prompts
us to
emphasise
A 36-year-old man, who had received a renal allograft 2tyears previously was admitted complaining of 3 weeks’ increasing breathlessnes’) and non-productive cough, night sweats, and weight-loss, which had not responded to conventional antimicrobial therapy. He had been n good health and was on a constant dose of prednisolone (7.5 mg/d) and azothiaprine (125 mg/d). Physical examination revealed only , tachypnœa, and fever. Chest X-ray showed patchy shadowof both bases. The clinical diagnosis of P. carinii pneumonia was confirmed bv identification of the organism in one of the specimens a bronchial brush biopsy done on the day of admission. He was S. C. Br. med. J. 1975, iii, 434. Robin E. D. , et al. New Engl. J. Med. 1973, 288, 292. 1. Walzer, P. D., Perl D. P., Krogstad, D. J., Rawson, P. G., Schultz, Ann intern Med 1974, 80, 83.
2.
It will be noted that there seems to be no relationship between the albumin and A.F.P. content of urine inasmuch as, in a given patient, samples of urine containing either 370 or 3600 ng/ml A.F.P. show approximately 30 mg/dl albumin, and conversely, in another patient, urines with either 30 or 300 mg/dl albumin contain 90-120 ng/ml A.F.P. However, there does seem to be a relationship between blood level and urinary level of A.F.P. as manifested in Ma. (blood 640 000 ng/ml, urine 1500 ng/ml), Mu. (blood 350 000 ng/ml, urine 300-3600 ng/ml) and Bu. (blood 54-104 000 ng/ml urine 110-165 ng/ml), but not in patients Kam. and Be. Purves. has also noted the presence of A.F.P. in urine of hepatoma patients 1. 2. 3.
1. Allen
M
G.,
’Labstix’, Ames Company, Elkhart, Indiana, U.S.A.
Gitlin, D. Boesman, M. J. clin. Invest. 1966, 45, 1826. Linder, E., Seppälä, M. Acta path. microbiol. scand. 1968, 73, 565. Okon, E., Rosenmann, T., Dishon, T., Boss, J. H. Br. J. Cancer, 1973, 27, 362.
4. Purves, L. R. Personal communication.