886
No indication of a protective effect of adjuvant chemotherapy was in this study with combined chemoLherapy and radiotherapy, although the number of patients, the treatment schedule, and the design and quality of follow-up were presumably similar to that of the Swedish study, but in which chemotherapy was combined with seen
radiotherapy. Danish Cancer Registry, Institute of Cancer Epidemiology, 2100 Copenhagen, Denmark
MICHAEL ANDERSSON HANS H. STORM
possibility that injecting 60 mg papaverine to men with non-organic impotence might itself induce a prolonged erection. This complication was reported in 27% of patients when 80 mg doses were used early in our experience with this drug.2 We recommend the avoidance of such high doses of papaverine in screening tests for impotence. 8 mg, which does not carry the risk of prolonged erection, is enough to study the penile arteries,3 and to study erectile capacity this test with low-dose of papaverine can be accompanied by visual sexual stimulation and, if necessary, artificial the
’
Danish Breast Cancer
Cooperative Group,
Copenhagen
HENNING T. MOURIDSEN
Rapid identification of Staphylococcus strains without clumping factor, protein A, or DNAse
aureus
SIR,-Dr Neville and colleagues (Aug 24, p 518) report a delay in recognition of infection with methicillin-resistant Staphylococcus aureus because the particular strains involved did not produce clumping factor, protein A, or DNAse, and they advocate the use of the tube coagulase test to detect similar strains. There are several disadvantages of this test in routine practice in that it requires reading at 4 and 24 h and it may sometimes give false-positive and false-negative results, depending on the source of plasma used.We have evaluated2 a new commercial kit needing only 2 h incubation and including a test that provides results equivalent to the tube coagulase test with substantial methodological advantages. The ’Rapidec Staph’ (bioMerieux, Basingstoke, UK) is a micromethod designed to identify isolates of clinically important staphylococci. It includes
a
test
for
an
enzyme called
aurease
that in
our
hands
was
highly sensitive and specific for tube-coagulase-positive strains of S aureus. All 79 tube-coagulase-positive clinical isolates of S aureus (including 17 clumping-factor-negative strains) were aureasepositive and 8 previously described rare tube-coagulase-negative, DNAse-positive variants3 were aurease-negative. Additionally, we were able to adapt this assay for direct use on blood culture broths containing gram-positive cocci.4 This technique, which is now part of our routine blood culture practice, allows rapid detection of tube-coagulase-positive S aureus strains at the time of subculture onto solid media, at least 24 h earlier than conventional methods. There is an alternative method for rapid identification of S aureus from blood culture which uses the thermonuclease reaction.s Neville and colleagues do not mention this reaction with their strains, but since they were DNAse negative they may also have been thermonuclease negative, thus limiting the usefulness of this test. The rapidec method applied to blood culture would have been of use in at least two of the four patients Neville and colleagues describe, providing an early indication of the presence of S aureus and emphasising the importance of the methicillin resistance subsequently found on subculture. M. B. PRENTICE Public Health Laboratory, C. GEARY Leicester Royal Infirmary, Leicester LE1 5WW, UK C. J. MITCHELL Sperber WH, Tatini SR. Interpretation of the tube coagulase test for identification of Staphylococcus aureus. Appl Microbiol 1975; 29: 502-05. 2. Geary C, Stevens M. A rapid test to detect the most clinically significant Staphylococcus species. Med Lab Sci 1991; 48: 99-105 3. Stevens M, Geary C. Comparative evaluation of a latex test for the identification of Staphylococcus aureus. Eur J Clin Microbiol Infect Dis 1989; 8: 153-56. 4. Mitchell CJ, Geary C, Stevens M. Detection of Staphylococcus aureus in blood 1.
cultures: evaluation of a two hour method. Med Lab Sci 1991; 48: 106-09. 5. Madison BM, Baselski VS. Rapid identification of Staphylococcus aureus in blood culture by thermonuclease testing. J Clin Microbiol 1983; 18: 722-24.
latrogenic priapism SIR,-Mr Vale and his colleagues (June 22, p 1991) discuss a possible link between intracavemous papaverine and intracavemous benzodiazepine, which could carry the risk of iatrogenic priapism. Anxiety is an important feature of impotence, both during sexual performance and in the clinic; the excessive release of adrenaline prevents relaxation of penile smooth muscled Although it is logical to think that decreasing anxiety with diazepam might enhance the local action of papaverine, one cannot exclude
erection. In rare cases when excessive anxiety might impede investigations, we prefer to use a beta-blocker (acebutolol 200 mg, 1 h before examination); this does not interfere locally with the erectile process.1,4 Patients should not be allowed to leave the clinic before detumescence. If this has not happened within 2 h an intracavemous injection of phenylephrine 1 mg should be given, followed, if necessary, by drainage from the cavernous bodies via a 19F catheter. When done within 3 h of an erection this approach prevents local complications.s Centre d’Etudes et de Recherches de l’Impuissance, Paris 75016, France
RONALD VIRAG
1.
Virag R. Papaverine et impuissance: la voie pharmacologique. Paris: Editions CERI,
2.
Virag R, Bouilly P, Daniel C, Virag H. Intracavernous injection of papaverine and other vasoactive drugs: a new era in the diagnosis and treatment of impotence. In: Proceedings of the First World Meeting on Impotence. Paris: Editions CERI,
1987.
1985. 187-94.
Virag R, Bouilly P, Daniel C. Signification de l’indice depression et intérêt du Minitest à la papaverine J Mal Vasc 1987; 12: 40-55. 4. Virag R. Human penile erection: an extensive study of vasoactive drugs. J Urol 1985; 133 (part 2): 311. 5. Virag R. About pharmacologically induced prolonged erection Lancet 1985; ii: 519. 3.
Juvenile
gigantism plus polyostotic fibrous dysplasia in the Tegernsee giant
SIR,-In 1876 25-year-old Thomas Hasler, the "Tegemsee giant", died. His height was 2-35 m (fig 1). His skeleton is in the Institute of Pathology at Munich University. Radiological and histological examination provides evidence of two possibly associated disorders. The Tegemsee giant is reported to have been a normally developing boy till the age of 9, when he started to grow very rapidly, being 1 ’62 m tall by the age of 12 years. Left-sided fractures of the fibula and femoral head (due to minor inury) at age 14 healed well. With advancing age, his skull enlarged enormously (fig 2). His skin was reported to be exceptionally pale. At the age of 25 he suddenly died with clinical features of acute cerebral distress (a detailed description of his life will be published elsewhere). On radiological examination all bones of the skull were extensively multicystic and transformed (fig 3), the most prominent alterations involving the left mandibula and the left forehead. The left frontal bone was 7 cm thick. Radiographs and inspection of the skull revealed the sella turcica as being much enlarged and partly excavated by a cystic defect. Roentgenograms of arms and legs disclosed open growth plates on both sides. On the left side, multiple well-delineated cystic osteolyses were present in tibia, fibula, femur, humerus, metacarpal IV, and the iliac bones while the right side showed unremarkable bone structures. Histological examination of a bone tissue specimen from the skull revealed trabecular bone made up exclusively of immature, woven bone, a typical feature of fibrous dysplasia.! These radiological and histological findings suggest that the Tegemsee giant had juvenile gigantism caused by a growthhormone-producing tumour of the hypophysis (as evidenced by the enlarged sella turcica). The open epiphyseal growth plates seem to be due to a lack of gonadotropins and the pale skin to reduced melanotropin production, both probably attributable to the expansive tumour growth. He also had polyostotic fibrous dysplasia of the skull and several other bones on the left side. To the best of our knowledge this association has not been described previously. Despite some similarities, this case does not fit the classic pattern of Albright’s syndrome, with fibrous dysplasia and multiple
887
Fig 1-Tegernsee giant’s skeleton compared with that of
a
normal individual.
Fig 2-Skull (photograph taken in 1876).
Fig 3-Sagittal computed tomographic scan demonstrating extensive multicystic transformation of bone. endocrine dysfunction, usually in young females.2 The late onset of continuing growth contrasts strikingly with the well-known syndrome, which usually presents with early onset of rapid growth and typically terminates by premature closure of the growth plates. The Tegemsee giant may have had a hitherto unreported syndrome-or the two disorders may have developed fortuitously. It may be more reasonable to conclude that continuous excessive growth hormone production stimulated fibrous dysplastic bone
growth. Institute of Pathology, University of Munich, 8000 Munich 2, Germany
ANDREAS NERLICH OLIVER PESCHEL UDO LÖHRS
Institute for Anthropology, University of Munich
FRANZ PARSCHE
Institute for Legal Medicine, University of Munich
PETER BETZ
after for multiple pituitary insufficiency surgery craniopharyngioma in childhood and a history of heat intolerance had his temperature measured twice a day at home for 16 days, during which there was a heatwave (July, 1991). He received replacement with hydrocortisone and thyroxine. As the figure
shows, his rectal temperature in the afternoon correlated
very
strongly with air temperature (Danish Meteorological Institute). Morning temperatures were all below 32-7°C (not shown). He had no signs of infection.
1. Harris WH, Dudley H Jr, Barry RJ. The natural history of fibrous dysplasia. J Bone Jt Surg 1962; 44A: 207-33. 2. Albright FA, Hampton AO, Smith P. Syndrome characterized by osteitis fibrosa, disseminate areas of pigmentation and endocrine dysfunction, with precocious puberty in females. N Engl JMed 1937; 216: 727-46.
Growth hormone deficiency and
hyperthermia SiR,—Patients with growth hormone (GH) insufficiency may have reduced sweating.l,2 Evaporation of sweat from the skin contributes to thermoregulation but we are not aware of reports on impaired regulation of body temperature in GH-deficient patients. Here, we report on three GH-deficient patients with unexplained hyperthermia. Reduced sweating capacity was demonstrated by pilocarpine iontophoresis, the values being 60-5, 18 5, and 9-2 mg over 30 min (for men, normal values range from 59 to 260 mg [median 135]). A 25-year-old
man with multiple pituitary insufficiency of origin had received replacement therapy with hydrocortisone, thyroxine, and testosterone. He had been admitted to hospital three times with unexplained hyperthermia (41 -1,40-8,
unknown
and 411 °C) and no infectious foci had been detected. In a similar case, a 19-year-old man with a history of problems in regulating body temperature since early childhood was admitted to hospital because of hyperthermia. He had no signs of infection and there was no leucocytosis. His temperature rose to 38-7°C on the first day but returned to normal within 2 days. A 65-year-old man with
Daily rectal temperatures
at 1700
hours,
at home after 30 min
rest.
to
Air temperatures are means of continuous measurements during 3 h up 1500 hours. Humidity was 50-95%.
We think that reduced sweating capacity caused hyperthermia in these non-GH-treated patients with GH deficiency. However, we cannot exclude other factors. A role for GH in sweating and thermoregulation should be explored. Department of Growth and Reproduction,
Rigshospitalet, Univerity of Copenhagen, DK-2100 Copenhagen, Denmark
ANDERS JUUL NIELS E. SKAKKEBAEK
1. Pedersen SA, Welling J, Michaelsen KF, Jørgensen JO, Christiansen J S, Skakkebaek NE. Reduced sweating in adults with growth hormone deficiency. Lancet 1989; ii: 681-82. 2. Main K, Nilsson KO, Skakkebaek NE. Influence of sex and growth hormone deficiency on sweating. Scand J Clin Lab Invest (in press).
No indication of a protective effect of adjuvant chemotherapy was in this study with combined chemoLherapy and radiotherapy, although the number of patients, the treatment schedule, and the design and quality of follow-up were presumably similar to that of the Swedish study, but in which chemotherapy was combined with seen
radiotherapy. Danish Cancer Registry, Institute of Cancer Epidemiology, 2100 Copenhagen, Denmark
MICHAEL ANDERSSON HANS H. STORM
possibility that injecting 60 mg papaverine to men with non-organic impotence might itself induce a prolonged erection. This complication was reported in 27% of patients when 80 mg doses were used early in our experience with this drug.2 We recommend the avoidance of such high doses of papaverine in screening tests for impotence. 8 mg, which does not carry the risk of prolonged erection, is enough to study the penile arteries,3 and to study erectile capacity this test with low-dose of papaverine can be accompanied by visual sexual stimulation and, if necessary, artificial the
’
Danish Breast Cancer
Cooperative Group,
Copenhagen
HENNING T. MOURIDSEN
Rapid identification of Staphylococcus strains without clumping factor, protein A, or DNAse
aureus
SIR,-Dr Neville and colleagues (Aug 24, p 518) report a delay in recognition of infection with methicillin-resistant Staphylococcus aureus because the particular strains involved did not produce clumping factor, protein A, or DNAse, and they advocate the use of the tube coagulase test to detect similar strains. There are several disadvantages of this test in routine practice in that it requires reading at 4 and 24 h and it may sometimes give false-positive and false-negative results, depending on the source of plasma used.We have evaluated2 a new commercial kit needing only 2 h incubation and including a test that provides results equivalent to the tube coagulase test with substantial methodological advantages. The ’Rapidec Staph’ (bioMerieux, Basingstoke, UK) is a micromethod designed to identify isolates of clinically important staphylococci. It includes
a
test
for
an
enzyme called
aurease
that in
our
hands
was
highly sensitive and specific for tube-coagulase-positive strains of S aureus. All 79 tube-coagulase-positive clinical isolates of S aureus (including 17 clumping-factor-negative strains) were aureasepositive and 8 previously described rare tube-coagulase-negative, DNAse-positive variants3 were aurease-negative. Additionally, we were able to adapt this assay for direct use on blood culture broths containing gram-positive cocci.4 This technique, which is now part of our routine blood culture practice, allows rapid detection of tube-coagulase-positive S aureus strains at the time of subculture onto solid media, at least 24 h earlier than conventional methods. There is an alternative method for rapid identification of S aureus from blood culture which uses the thermonuclease reaction.s Neville and colleagues do not mention this reaction with their strains, but since they were DNAse negative they may also have been thermonuclease negative, thus limiting the usefulness of this test. The rapidec method applied to blood culture would have been of use in at least two of the four patients Neville and colleagues describe, providing an early indication of the presence of S aureus and emphasising the importance of the methicillin resistance subsequently found on subculture. M. B. PRENTICE Public Health Laboratory, C. GEARY Leicester Royal Infirmary, Leicester LE1 5WW, UK C. J. MITCHELL Sperber WH, Tatini SR. Interpretation of the tube coagulase test for identification of Staphylococcus aureus. Appl Microbiol 1975; 29: 502-05. 2. Geary C, Stevens M. A rapid test to detect the most clinically significant Staphylococcus species. Med Lab Sci 1991; 48: 99-105 3. Stevens M, Geary C. Comparative evaluation of a latex test for the identification of Staphylococcus aureus. Eur J Clin Microbiol Infect Dis 1989; 8: 153-56. 4. Mitchell CJ, Geary C, Stevens M. Detection of Staphylococcus aureus in blood 1.
cultures: evaluation of a two hour method. Med Lab Sci 1991; 48: 106-09. 5. Madison BM, Baselski VS. Rapid identification of Staphylococcus aureus in blood culture by thermonuclease testing. J Clin Microbiol 1983; 18: 722-24.
latrogenic priapism SIR,-Mr Vale and his colleagues (June 22, p 1991) discuss a possible link between intracavemous papaverine and intracavemous benzodiazepine, which could carry the risk of iatrogenic priapism. Anxiety is an important feature of impotence, both during sexual performance and in the clinic; the excessive release of adrenaline prevents relaxation of penile smooth muscled Although it is logical to think that decreasing anxiety with diazepam might enhance the local action of papaverine, one cannot exclude
erection. In rare cases when excessive anxiety might impede investigations, we prefer to use a beta-blocker (acebutolol 200 mg, 1 h before examination); this does not interfere locally with the erectile process.1,4 Patients should not be allowed to leave the clinic before detumescence. If this has not happened within 2 h an intracavemous injection of phenylephrine 1 mg should be given, followed, if necessary, by drainage from the cavernous bodies via a 19F catheter. When done within 3 h of an erection this approach prevents local complications.s Centre d’Etudes et de Recherches de l’Impuissance, Paris 75016, France
RONALD VIRAG
1.
Virag R. Papaverine et impuissance: la voie pharmacologique. Paris: Editions CERI,
2.
Virag R, Bouilly P, Daniel C, Virag H. Intracavernous injection of papaverine and other vasoactive drugs: a new era in the diagnosis and treatment of impotence. In: Proceedings of the First World Meeting on Impotence. Paris: Editions CERI,
1987.
1985. 187-94.
Virag R, Bouilly P, Daniel C. Signification de l’indice depression et intérêt du Minitest à la papaverine J Mal Vasc 1987; 12: 40-55. 4. Virag R. Human penile erection: an extensive study of vasoactive drugs. J Urol 1985; 133 (part 2): 311. 5. Virag R. About pharmacologically induced prolonged erection Lancet 1985; ii: 519. 3.
Juvenile
gigantism plus polyostotic fibrous dysplasia in the Tegernsee giant
SIR,-In 1876 25-year-old Thomas Hasler, the "Tegemsee giant", died. His height was 2-35 m (fig 1). His skeleton is in the Institute of Pathology at Munich University. Radiological and histological examination provides evidence of two possibly associated disorders. The Tegemsee giant is reported to have been a normally developing boy till the age of 9, when he started to grow very rapidly, being 1 ’62 m tall by the age of 12 years. Left-sided fractures of the fibula and femoral head (due to minor inury) at age 14 healed well. With advancing age, his skull enlarged enormously (fig 2). His skin was reported to be exceptionally pale. At the age of 25 he suddenly died with clinical features of acute cerebral distress (a detailed description of his life will be published elsewhere). On radiological examination all bones of the skull were extensively multicystic and transformed (fig 3), the most prominent alterations involving the left mandibula and the left forehead. The left frontal bone was 7 cm thick. Radiographs and inspection of the skull revealed the sella turcica as being much enlarged and partly excavated by a cystic defect. Roentgenograms of arms and legs disclosed open growth plates on both sides. On the left side, multiple well-delineated cystic osteolyses were present in tibia, fibula, femur, humerus, metacarpal IV, and the iliac bones while the right side showed unremarkable bone structures. Histological examination of a bone tissue specimen from the skull revealed trabecular bone made up exclusively of immature, woven bone, a typical feature of fibrous dysplasia.! These radiological and histological findings suggest that the Tegemsee giant had juvenile gigantism caused by a growthhormone-producing tumour of the hypophysis (as evidenced by the enlarged sella turcica). The open epiphyseal growth plates seem to be due to a lack of gonadotropins and the pale skin to reduced melanotropin production, both probably attributable to the expansive tumour growth. He also had polyostotic fibrous dysplasia of the skull and several other bones on the left side. To the best of our knowledge this association has not been described previously. Despite some similarities, this case does not fit the classic pattern of Albright’s syndrome, with fibrous dysplasia and multiple
887
Fig 1-Tegernsee giant’s skeleton compared with that of
a
normal individual.
Fig 2-Skull (photograph taken in 1876).
Fig 3-Sagittal computed tomographic scan demonstrating extensive multicystic transformation of bone. endocrine dysfunction, usually in young females.2 The late onset of continuing growth contrasts strikingly with the well-known syndrome, which usually presents with early onset of rapid growth and typically terminates by premature closure of the growth plates. The Tegemsee giant may have had a hitherto unreported syndrome-or the two disorders may have developed fortuitously. It may be more reasonable to conclude that continuous excessive growth hormone production stimulated fibrous dysplastic bone
growth. Institute of Pathology, University of Munich, 8000 Munich 2, Germany
ANDREAS NERLICH OLIVER PESCHEL UDO LÖHRS
Institute for Anthropology, University of Munich
FRANZ PARSCHE
Institute for Legal Medicine, University of Munich
PETER BETZ
after for multiple pituitary insufficiency surgery craniopharyngioma in childhood and a history of heat intolerance had his temperature measured twice a day at home for 16 days, during which there was a heatwave (July, 1991). He received replacement with hydrocortisone and thyroxine. As the figure
shows, his rectal temperature in the afternoon correlated
very
strongly with air temperature (Danish Meteorological Institute). Morning temperatures were all below 32-7°C (not shown). He had no signs of infection.
1. Harris WH, Dudley H Jr, Barry RJ. The natural history of fibrous dysplasia. J Bone Jt Surg 1962; 44A: 207-33. 2. Albright FA, Hampton AO, Smith P. Syndrome characterized by osteitis fibrosa, disseminate areas of pigmentation and endocrine dysfunction, with precocious puberty in females. N Engl JMed 1937; 216: 727-46.
Growth hormone deficiency and
hyperthermia SiR,—Patients with growth hormone (GH) insufficiency may have reduced sweating.l,2 Evaporation of sweat from the skin contributes to thermoregulation but we are not aware of reports on impaired regulation of body temperature in GH-deficient patients. Here, we report on three GH-deficient patients with unexplained hyperthermia. Reduced sweating capacity was demonstrated by pilocarpine iontophoresis, the values being 60-5, 18 5, and 9-2 mg over 30 min (for men, normal values range from 59 to 260 mg [median 135]). A 25-year-old
man with multiple pituitary insufficiency of origin had received replacement therapy with hydrocortisone, thyroxine, and testosterone. He had been admitted to hospital three times with unexplained hyperthermia (41 -1,40-8,
unknown
and 411 °C) and no infectious foci had been detected. In a similar case, a 19-year-old man with a history of problems in regulating body temperature since early childhood was admitted to hospital because of hyperthermia. He had no signs of infection and there was no leucocytosis. His temperature rose to 38-7°C on the first day but returned to normal within 2 days. A 65-year-old man with
Daily rectal temperatures
at 1700
hours,
at home after 30 min
rest.
to
Air temperatures are means of continuous measurements during 3 h up 1500 hours. Humidity was 50-95%.
We think that reduced sweating capacity caused hyperthermia in these non-GH-treated patients with GH deficiency. However, we cannot exclude other factors. A role for GH in sweating and thermoregulation should be explored. Department of Growth and Reproduction,
Rigshospitalet, Univerity of Copenhagen, DK-2100 Copenhagen, Denmark
ANDERS JUUL NIELS E. SKAKKEBAEK
1. Pedersen SA, Welling J, Michaelsen KF, Jørgensen JO, Christiansen J S, Skakkebaek NE. Reduced sweating in adults with growth hormone deficiency. Lancet 1989; ii: 681-82. 2. Main K, Nilsson KO, Skakkebaek NE. Influence of sex and growth hormone deficiency on sweating. Scand J Clin Lab Invest (in press).
