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TORULOPSIS GLABRATA SEPTICÆMIA TREATED WITH 5-FLUOROCYTOSINE
839 parents stop having children as soon as a boy is born, completed families of size one will have predominantly male offspring, while the first two children in families of three or more will be females. Clearly this will not alter the sexratio in the population, but will alter the distribution of sex in relation to family size which is the gist of Mr. Mussalli’s letter (Jan. 3, p. 42). That this idea is not new was kindly pointed out to me by Professor Bell.1 Section of Medical Genetics,
University Hospital, Saskatoon, Canada.
M. H. K. SHOKEIR.
EDUCATION PROBLEMS IN THE U.S.A.
SIR,-Your U.S.A. correspondent (March 21, p. 609), discussing the American urban problems of education, asks, Why not rebuild the ghetto schools and make them so good, with Federal money, that they will be schools to resort to rather than to be repelled from ?" Why not, "
indeed ? Has he forgotten that it is not the physical buildings that make the school but the students and the people within ? Yes, a massive infusion of funds is necessary to establish high-quality schools throughout the U.S.A. But the funds must be spent on early supplementation of education such as Project Headstart, and on continuance funding, so that adequately salaried and imaginative faculty can set up good programmes and teach. Your correspondent is right when he says " No solutions are going to be
easv Los Angeles, California.
STEVEN H. LAMM.
ABSENCE OF FRUCTOSE-INDUCED HYPERURICÆMIA IN MEN
SIR,-In 1967, Perheentupa and Raivio2 described fructose-induced hyperuricsemia in children with hereditary fructose intolerance and in control pxdiatric patients. These investigators believed that the hyperuricxmia resulted from increased uric-acid production following fructose administration. Fructose solutions are often used for intravenous calorie and fluid administration. Resultant hyperuricoemia may accentuate the symptoms of gout or accelerate the formation of renal calculi. We have administered 100 g. of fructose intravenously (as a 10% solution) to ten adult male patients (average age 25 years) who had recovered completely from extensive thermal injury. Five patients were given the fructose in 2 hours at a rate of 500 ml. per hour, and the remaining five received a constant intravenous infusion during the 5-hour test period, at a rate of 200 ml. per hour. Blood for uric-acid assay was obtained at 0, 1/2, 1, 2, 3, 4, and 5 hours following commencement of the intravenous infusion. One patient had mild hyperuricxmia before the infusion, with a serum-uric-acid of 6-68 mg. per 100 ml. (normal range 4-09-6-07 mg. per 100 ml.). However, none of the patients demonstrated any significant rise in uric acid during the test period (see below).
This of
study in young adults does not confirm the findings Perheentupa and Raivio in pasdiatric patients, and 1.
2.
Thomas, M. H. Br. med. J. 1951, i, 733. Perheentupa, J., Raivio, K. Lancet, 1967, ii, 528.
indicates that 10% fructose solutions may be administered intravenously to adults without resultant hyperuricaemia. U.S. Army Institute of Surgical Research, Brooke Army Medical Center P. WILLIAM CURRERI Fort Sam Houston, BASIL A. PRUITT, JR. Texas 78234.
CORYNEBACTERIUM ULCERANS INFECTIONS SiR,-In their letter of Feb. 7 (p. 298), Dr. Fakes and Dr. Downham describe a case of Corynebacterium infection with unusually severe toxic manifestations. The Public Health Laboratory at Bath serves a predominantly rural population with ready access to, and often a predilection for, raw milk. Cases of C. ulcerans infection are encountered in small numbers in most years, but none has so far been so severely affected as Fakes and Downham’s case. It might be relevant that this patient was treated with penicillin rather than erythromycin. For several years erythromycin has been suggested as the drug of choice for cases diagnosed in Bath, and the response has been uniformly satisfactory. Prompt relief of symptoms is matched, by bacteriological clearance, from the nose as well as from the throat. On several occasions positive cultures have been obtained from patients who had already been treated for several days with penicillin. A change to erythromycin has invariably been followed by elimination of the infection. Erythromycin has been regarded as the drug of choice for diphtheria,’ and in a small group of infections seen during 1968 the same prompt response to erythromycin was noted, as well as clearance of one patient whose throat swab still yielded C. diphtheriae after several days’ penicillin treatment. It seems fair to suggest that erythromycin has distinct advantages over penicillin for the treatment of infections due to C. ulcerans as well as C. diphtheria, since in both cases the persistence of viable organisms in the nasopharynx may be associated with continued production of diffusible toxins. Public Health Laboratory, Bath.
P. G. MANN.
TORULOPSIS GLABRATA SEPTICÆMIA TREATED WITH 5-FLUOROCYTOSINE SIR,-We should like to report a case of Torulopsis glabrata septicaemia, successfully treated with the antifungal agent, 5-fluorocytosine. The patient was a woman of 35 years with poorly controlled diabetes, she was admitted to hospital on Dec. 13, 1969, with a clinical diagnosis of diabetic precoma. Following stabilisation of her diabetes she became profoundly shocked, with a clinical picture suggestive of gram-negative septicaemia. The abdomen was somewhat distended and bowel sounds were diminished. The shock was partially controlled by rehydration and antibiotics, but her abdominal distension increased. On Dec. 16, bilateral grid-iron incisions were made under local anxsthesia, and approximately half a litre of seropurulent sterile fluid was drained; no cause for this was discovered. Thereafter she had a series of severe electrolyte crises. Subsequently she developed peritoneal infection, septicaemia due to an Escherichia strain, and a urinary-tract infection with E. coli. She was treated with adrenocorticosteroids and a number of antibiotics, including chloramphenicol ; she had many intravenous infusions and an indwelling bladder catheter. Yeasts were isolated in heavy growth from urine specimens from the fourth day of her admission, and from four blood specimens taken on separate days. These "
1.
"
Garrod, L. P., O’Grady, F. Antibiotics and Chemotherapy; p. 169. London, 1968.
840 isolates
were
identified by Dr. 1. G.
Murray
as
Torulopsi
glabrata. On Dec. 21 a full laparotomy was carried out, but, apart from the seroturbid fluid, showed no abnormality othe] than a small pancreatic pseudocyst. There was no evidence of fat necrosis. Since few superficial veins were by this time available foi administration of amphotericin B, and since there was some suggestion of diabetic nephropathy (previous history of lefl renal carbuncle in 1956), treatment was started with 5fluorocytosine (minimum inhibitory concentration for the yeast, 0-25 g. per ml.). The dose was of 9 g. daily (200 mg. per kg.) by mouth. Serum concentrations of 5-fluorocytosine were estimated on two occasions as 20 g. per ml. and 10 g. per ml. In addition, 100 mg. of amphotericin B was instilled into the bladder daily. Treatment was continued for ten days, and at the end of this time the patient was well enough to return home. Blood and urine cultures yielded no further growth of yeasts. No depression of the blood-count or impairment of liver-function tests was observed. Torulopsis glabrata is a common vaginal commensal which occasionally causes urinary-tract infection and rarely septicaemia in debilitated patients. Successful treatment with amphotericin B has been reported. 5-fluorocytosine, which can be administered orally, has been used with good results in Candida septicaemia and in cryptococcal meningitis 2,3; and it appears to have eradicated the blood infection with Torulopsis in the present case, though it is possible that clearing of the bladder infection, in which urinary 5-fluorocytosine was assisted by amphotericin B, contributed to this. Toxic effects4 were not observed during this short ("0111’<::1"
with mnc1f’1’tf’ h)f)nf-1<*vpt<:
Departments of Surgery and Bacteriology, Royal Infirmary, Bristol.
A. J. WEBB D. C. E. SPELLER K. G. BUCKLER.
A NEW MALFORMATION SYNDROME? a sibship of five males and three females, three boys and one girl were born with a syndrome which has apparently not been described before. Only two of the affected children and two of the normal sibs (one boy and one girl in each case) are still alive and have been examined. The clinical features (see accompanying figure) were as follows:
SIR,-In
(1) Extensive bone deficiencies in all limbs ; (2) scarcity of hair the whole body; (3) large, thin, protruding, and deformed pinnas (helix partly unrolled); (4) abnormal dentition (widely spaced teeth, most of them small and conical; permanence of some deciduous teeth and absence of some permanent ones); (5) hypoplastic nipples and areolas; (6) discrete simple goitre; (7) impaired mental performance; (8) sexual underdevelopment; (9) hypoplastic nails; (10) gynaecomastia (discrete); (11) growth retardation; (12) unilateral (right) incomplete hare-lip; (13) electroencephalographic abnormalities; (14) electrocardiographic abnormalities; (15) metabolic abnormalities. Signs 8-13 were only present in the boy. (The girl has over
or toes at all.) Only the girl had electrocardioabnormalities. Both had simple goitres, but this graphic may have been fortuitous. Mental impairment, which was found in both, may have been of cultural origin. It is thus doubtful whether these signs (8-14) are all components of the syndrome. It is postulated that this syndrome is due to the homozygosity of a rare autosomal-recessive gene. no
syndrome.
Metabolic Abnormalities
Paper chromatography of the urine of the two patients an excess (larger in the boy than in the girl) of tryptophan and/or tyrosine. This may be a characteristic of the syndrome. The patients, and their parents, refused revealed
to
aHow blood
to
be taken for further studies.
Dermatoglyphics Dermatoglyphic analysis two
of the upper extremities of the
patients revealed the following:
In the boy the left hand had only two metacarpals and two fingers. One of the fingers had a tented arch and the other a radial loop (RC7). The remainder of the palm showed unusual lines, without the normal flexion creases, and with only one digital triradius. Near the most distal bracelet crease there was a simple whorl with an atypical core. The distal part of the right limb was represented only by an elongated appendage (without fingers). On this there were two areas with atypical lines (some of them interrupted), surrounded by non-ridged skin. In the girl the terminal appendage on the left upper limb had no fingers, but showed palm-like interrupted lines. At the end of the appendage there was a pattern resembling a double whorl without triradii. On the right side there was a ball-like appendage with interrupted and dissociated ridges.
These data represent extensive dermatoglyphic disturbThe parents, however, had normal dermatoglyphics.
ances.
Chromosomes Chromosome analysis was performed on cultured leucocytes from the venous blood of three members of the family, using a slight modification of a widely used tech-
nique.1 All the cells selected for analysis were photographed for chromosome counting and karyotyping. Patau’s counting procedure was used when possible. The three individuals investigated had normal karyotypes.
fingers
English, M. P. Rev. med. vet. Myc. 1967, 6, 103. Tassel, D., Madoff, M. A. J. Am. med. Ass. 1968, 206, 830. Watkins, J. S., Campbell, M. J., Gardner-Medwin, D., Ingham, H. R., Murray, I. G. Br. med. J. 1969, iii, 29. 4. Grunberg, E., Prince, H. N., Utz, J. P. Proceedings of Fifth International Congress of Chemotherapy (edited by K. H. Spitzy and H. Haschek); vol. IV, p. 69. Vienna, 1967. 1. 2. 3.
Brother and sister with the malformation
Unfortunately technical difficulties made it impossible to more cells from the father, or the cells of the boy. The patients and their parents did not
examine affected allow us
to
take any
more
blood.
A full
description of this syndrome will appear in the American _7ournal of Human Genetics. This work was sponsored by the Fund for Overseas Research Grants and Education Inc., the Rockefeller Foundation, the National Research Council of Brazil, the Calouste Gulbenkian 1. Moorhead, P.
Hungerford,
S., Nowell, P. C., Mellman, W. J., Battips, D. M., Expl Cell Res. 1960, 20, 613.
D. A.
University Hospital, Saskatoon, Canada.
M. H. K. SHOKEIR.
EDUCATION PROBLEMS IN THE U.S.A.
SIR,-Your U.S.A. correspondent (March 21, p. 609), discussing the American urban problems of education, asks, Why not rebuild the ghetto schools and make them so good, with Federal money, that they will be schools to resort to rather than to be repelled from ?" Why not, "
indeed ? Has he forgotten that it is not the physical buildings that make the school but the students and the people within ? Yes, a massive infusion of funds is necessary to establish high-quality schools throughout the U.S.A. But the funds must be spent on early supplementation of education such as Project Headstart, and on continuance funding, so that adequately salaried and imaginative faculty can set up good programmes and teach. Your correspondent is right when he says " No solutions are going to be
easv Los Angeles, California.
STEVEN H. LAMM.
ABSENCE OF FRUCTOSE-INDUCED HYPERURICÆMIA IN MEN
SIR,-In 1967, Perheentupa and Raivio2 described fructose-induced hyperuricsemia in children with hereditary fructose intolerance and in control pxdiatric patients. These investigators believed that the hyperuricxmia resulted from increased uric-acid production following fructose administration. Fructose solutions are often used for intravenous calorie and fluid administration. Resultant hyperuricoemia may accentuate the symptoms of gout or accelerate the formation of renal calculi. We have administered 100 g. of fructose intravenously (as a 10% solution) to ten adult male patients (average age 25 years) who had recovered completely from extensive thermal injury. Five patients were given the fructose in 2 hours at a rate of 500 ml. per hour, and the remaining five received a constant intravenous infusion during the 5-hour test period, at a rate of 200 ml. per hour. Blood for uric-acid assay was obtained at 0, 1/2, 1, 2, 3, 4, and 5 hours following commencement of the intravenous infusion. One patient had mild hyperuricxmia before the infusion, with a serum-uric-acid of 6-68 mg. per 100 ml. (normal range 4-09-6-07 mg. per 100 ml.). However, none of the patients demonstrated any significant rise in uric acid during the test period (see below).
This of
study in young adults does not confirm the findings Perheentupa and Raivio in pasdiatric patients, and 1.
2.
Thomas, M. H. Br. med. J. 1951, i, 733. Perheentupa, J., Raivio, K. Lancet, 1967, ii, 528.
indicates that 10% fructose solutions may be administered intravenously to adults without resultant hyperuricaemia. U.S. Army Institute of Surgical Research, Brooke Army Medical Center P. WILLIAM CURRERI Fort Sam Houston, BASIL A. PRUITT, JR. Texas 78234.
CORYNEBACTERIUM ULCERANS INFECTIONS SiR,-In their letter of Feb. 7 (p. 298), Dr. Fakes and Dr. Downham describe a case of Corynebacterium infection with unusually severe toxic manifestations. The Public Health Laboratory at Bath serves a predominantly rural population with ready access to, and often a predilection for, raw milk. Cases of C. ulcerans infection are encountered in small numbers in most years, but none has so far been so severely affected as Fakes and Downham’s case. It might be relevant that this patient was treated with penicillin rather than erythromycin. For several years erythromycin has been suggested as the drug of choice for cases diagnosed in Bath, and the response has been uniformly satisfactory. Prompt relief of symptoms is matched, by bacteriological clearance, from the nose as well as from the throat. On several occasions positive cultures have been obtained from patients who had already been treated for several days with penicillin. A change to erythromycin has invariably been followed by elimination of the infection. Erythromycin has been regarded as the drug of choice for diphtheria,’ and in a small group of infections seen during 1968 the same prompt response to erythromycin was noted, as well as clearance of one patient whose throat swab still yielded C. diphtheriae after several days’ penicillin treatment. It seems fair to suggest that erythromycin has distinct advantages over penicillin for the treatment of infections due to C. ulcerans as well as C. diphtheria, since in both cases the persistence of viable organisms in the nasopharynx may be associated with continued production of diffusible toxins. Public Health Laboratory, Bath.
P. G. MANN.
TORULOPSIS GLABRATA SEPTICÆMIA TREATED WITH 5-FLUOROCYTOSINE SIR,-We should like to report a case of Torulopsis glabrata septicaemia, successfully treated with the antifungal agent, 5-fluorocytosine. The patient was a woman of 35 years with poorly controlled diabetes, she was admitted to hospital on Dec. 13, 1969, with a clinical diagnosis of diabetic precoma. Following stabilisation of her diabetes she became profoundly shocked, with a clinical picture suggestive of gram-negative septicaemia. The abdomen was somewhat distended and bowel sounds were diminished. The shock was partially controlled by rehydration and antibiotics, but her abdominal distension increased. On Dec. 16, bilateral grid-iron incisions were made under local anxsthesia, and approximately half a litre of seropurulent sterile fluid was drained; no cause for this was discovered. Thereafter she had a series of severe electrolyte crises. Subsequently she developed peritoneal infection, septicaemia due to an Escherichia strain, and a urinary-tract infection with E. coli. She was treated with adrenocorticosteroids and a number of antibiotics, including chloramphenicol ; she had many intravenous infusions and an indwelling bladder catheter. Yeasts were isolated in heavy growth from urine specimens from the fourth day of her admission, and from four blood specimens taken on separate days. These "
1.
"
Garrod, L. P., O’Grady, F. Antibiotics and Chemotherapy; p. 169. London, 1968.
840 isolates
were
identified by Dr. 1. G.
Murray
as
Torulopsi
glabrata. On Dec. 21 a full laparotomy was carried out, but, apart from the seroturbid fluid, showed no abnormality othe] than a small pancreatic pseudocyst. There was no evidence of fat necrosis. Since few superficial veins were by this time available foi administration of amphotericin B, and since there was some suggestion of diabetic nephropathy (previous history of lefl renal carbuncle in 1956), treatment was started with 5fluorocytosine (minimum inhibitory concentration for the yeast, 0-25 g. per ml.). The dose was of 9 g. daily (200 mg. per kg.) by mouth. Serum concentrations of 5-fluorocytosine were estimated on two occasions as 20 g. per ml. and 10 g. per ml. In addition, 100 mg. of amphotericin B was instilled into the bladder daily. Treatment was continued for ten days, and at the end of this time the patient was well enough to return home. Blood and urine cultures yielded no further growth of yeasts. No depression of the blood-count or impairment of liver-function tests was observed. Torulopsis glabrata is a common vaginal commensal which occasionally causes urinary-tract infection and rarely septicaemia in debilitated patients. Successful treatment with amphotericin B has been reported. 5-fluorocytosine, which can be administered orally, has been used with good results in Candida septicaemia and in cryptococcal meningitis 2,3; and it appears to have eradicated the blood infection with Torulopsis in the present case, though it is possible that clearing of the bladder infection, in which urinary 5-fluorocytosine was assisted by amphotericin B, contributed to this. Toxic effects4 were not observed during this short ("0111’<::1"
with mnc1f’1’tf’ h)f)nf-1<*vpt<:
Departments of Surgery and Bacteriology, Royal Infirmary, Bristol.
A. J. WEBB D. C. E. SPELLER K. G. BUCKLER.
A NEW MALFORMATION SYNDROME? a sibship of five males and three females, three boys and one girl were born with a syndrome which has apparently not been described before. Only two of the affected children and two of the normal sibs (one boy and one girl in each case) are still alive and have been examined. The clinical features (see accompanying figure) were as follows:
SIR,-In
(1) Extensive bone deficiencies in all limbs ; (2) scarcity of hair the whole body; (3) large, thin, protruding, and deformed pinnas (helix partly unrolled); (4) abnormal dentition (widely spaced teeth, most of them small and conical; permanence of some deciduous teeth and absence of some permanent ones); (5) hypoplastic nipples and areolas; (6) discrete simple goitre; (7) impaired mental performance; (8) sexual underdevelopment; (9) hypoplastic nails; (10) gynaecomastia (discrete); (11) growth retardation; (12) unilateral (right) incomplete hare-lip; (13) electroencephalographic abnormalities; (14) electrocardiographic abnormalities; (15) metabolic abnormalities. Signs 8-13 were only present in the boy. (The girl has over
or toes at all.) Only the girl had electrocardioabnormalities. Both had simple goitres, but this graphic may have been fortuitous. Mental impairment, which was found in both, may have been of cultural origin. It is thus doubtful whether these signs (8-14) are all components of the syndrome. It is postulated that this syndrome is due to the homozygosity of a rare autosomal-recessive gene. no
syndrome.
Metabolic Abnormalities
Paper chromatography of the urine of the two patients an excess (larger in the boy than in the girl) of tryptophan and/or tyrosine. This may be a characteristic of the syndrome. The patients, and their parents, refused revealed
to
aHow blood
to
be taken for further studies.
Dermatoglyphics Dermatoglyphic analysis two
of the upper extremities of the
patients revealed the following:
In the boy the left hand had only two metacarpals and two fingers. One of the fingers had a tented arch and the other a radial loop (RC7). The remainder of the palm showed unusual lines, without the normal flexion creases, and with only one digital triradius. Near the most distal bracelet crease there was a simple whorl with an atypical core. The distal part of the right limb was represented only by an elongated appendage (without fingers). On this there were two areas with atypical lines (some of them interrupted), surrounded by non-ridged skin. In the girl the terminal appendage on the left upper limb had no fingers, but showed palm-like interrupted lines. At the end of the appendage there was a pattern resembling a double whorl without triradii. On the right side there was a ball-like appendage with interrupted and dissociated ridges.
These data represent extensive dermatoglyphic disturbThe parents, however, had normal dermatoglyphics.
ances.
Chromosomes Chromosome analysis was performed on cultured leucocytes from the venous blood of three members of the family, using a slight modification of a widely used tech-
nique.1 All the cells selected for analysis were photographed for chromosome counting and karyotyping. Patau’s counting procedure was used when possible. The three individuals investigated had normal karyotypes.
fingers
English, M. P. Rev. med. vet. Myc. 1967, 6, 103. Tassel, D., Madoff, M. A. J. Am. med. Ass. 1968, 206, 830. Watkins, J. S., Campbell, M. J., Gardner-Medwin, D., Ingham, H. R., Murray, I. G. Br. med. J. 1969, iii, 29. 4. Grunberg, E., Prince, H. N., Utz, J. P. Proceedings of Fifth International Congress of Chemotherapy (edited by K. H. Spitzy and H. Haschek); vol. IV, p. 69. Vienna, 1967. 1. 2. 3.
Brother and sister with the malformation
Unfortunately technical difficulties made it impossible to more cells from the father, or the cells of the boy. The patients and their parents did not
examine affected allow us
to
take any
more
blood.
A full
description of this syndrome will appear in the American _7ournal of Human Genetics. This work was sponsored by the Fund for Overseas Research Grants and Education Inc., the Rockefeller Foundation, the National Research Council of Brazil, the Calouste Gulbenkian 1. Moorhead, P.
Hungerford,
S., Nowell, P. C., Mellman, W. J., Battips, D. M., Expl Cell Res. 1960, 20, 613.
D. A.