- Email: [email protected]
ALVEOLI AND ABNORMAL SURFACTANT
1329
by abdominal discomfort and, in two cases, increases in pancreatic enzymes (all reproducible on re-challenge). In one published case of suspected alveolitis after nomifensine chest X-rays did not suggest altered lung structure, and lung function studies and biopsy were not done.2Two cases are mentioned in another study but without any details. 10 We conclude that nomifensine is a drug capable of inducing hypersensitivity alveolitis. Progression towards lung fibrosis cannot yet be excluded.
,
H. HAMM 1st Medical
Department,
J. AUMILLER
Marienkrankenhaus Hamburg, 2 Hamburg 76, West Germany
R. BÖHMER H. P. MISSMAHL
Israelitisches Krankenhaus Hamburg
U. FÜLLBRANDT H. FRENZEL
1. Dankbaar
H, Mudde AH. Fever and liver function disturbances as a result oftherapy with nomifensine. Net T Geneesk 1980; 124: 2184-86. 2. Hunziker T, Fehlmann U, Kummer H, et al. Arzneifieber auf das Antidepressivum Nomifensin (Alival). Schweiz Med Wschr 1980; 110: 1295-300. 3. Nielsen JL, Lund NO. Drug fever due to nomifensine treatment in patients with endogenous depression. Int Pharmacopsychiat 1981; 16: 66-68. 4. Brandes JW, Körst HA, Littmann KP. Gelbsucht nach Nomifensin. Med Welt 1980; 31: 1607-08. 5. Eckstein R, Riess H, Sauer H, Mempel W. Nomifensine-induced immune haemolytic anaemias. Klin Wschr 1981; 59: 567-69. 6. Bournerias F, Habibi B. Nomifensine-induced immune haemolytic anaemia and impaired renal function. Lancet 1979; ii: 95-96. 7. Lyloff K, Jersild C, Bacher T, Slot O. Massive intravascular haemolysis during treatment with nomifensine. Lancet 1982; ii: 41. 8. Prescott LF, Illingworth RN, Critchley JAJH, et al. Acute haemolysis and renal failure after nomifensine overdosage. Br Med J 1980; 281: 1392-93. 9. Garcia-Morteo O, Maldonado-Cocco JA. Lupus-like syndrome during treatment with nomifensine. Arthritis Rheum 1983; 26: 936. 10. Wälti M, Neftel K, Cohen M, De Weck AL, Perisic M. Nachweis von arzneimittelspezifischen IgE- und IgG-Antiköpern mittels RIA: klinische Bedeutung am Beispiel Nomifensin (Alival). Schweiz Med Wschr 1983; 113: 1865-67.
LEGIONNAIRES’ DISEASE IN STAFFORDSHIRE
SIR,-A 66-year-old man was admitted to Stafford General Infirmary on April 6, 1985. After 4 days as an inpatient on the top floor of the hospital he went to his son’s house in Huntingdon to convalesce (from a fractured sternum). He returned to Bradford on April 18, but on the journey home became delirious and had He was admitted to a local hospital and transferred the following day where the triad of mental confusion, gastroenteritis, and pneumonia suggested a diagnosis of legionnaires’ disease and erythromycin was started. The patient made an uneventful recovery. The initial legionella titre was below 1:8 but by May 8 the titre had risen three-fold. Any patient with atypical pneumonia should be treated with erythromycin without waiting for serological confirmation. Adherence to this policy led to the correct treatment of another case of legionnaires’ disease in this hospital, this one having no link with the Staffordshire epidemic. Talk of mystery viruses and undiscovered diseases misleads.
gastroenteritis. to
St Luke’s
Medical Unit, St Luke’s Hospital, Bradford BD5 0NA
on
J. R. STANILAND C. GLEW
J. PECHAN
ALVEOLI AND ABNORMAL SURFACTANT
SIR,-Dr Talbert and Dr Southall (March 30, p 727) suggest that alveoli lined with abnormal surfactant may collapse if their size is reduced below a critical radius determined by the minimum surface tension of the surfactant film. Their mathematical model is based on the assumption that alveoli are spheres lined with surfactant. However, alveoli are neither closed nor spherical, and during breathing little is known of how their area and shape change. They may shrink or convolute like a plastic bag, and probably they do both. The radius of the alveoli and the way in which this changes with volume will critically affect any mathematical model. Without details of alveolar shape and area it is not possible to construct an accurate mathematical model to explain
Fig I-Surface tensionlarea loop for surfactant at 37OC. Upper: lipid extract from human amniotic fluid (normal). Lower: lipid extracts of surfactant from five babies who died from cot death on 0 9% saline, spread dry.
the role of a defective surfactant in alveolar mechanics. It is also necessary to understand the surface properties during compression of "defective" surfactant. We present below some surface tension data collected on surfactant obtained from infants who have died suddenly and unexpectedly (cot death). When rapidly compressed at body temperature, normal surfactant will always reduce surface tension below 10 mN/m (fig 1). Often the film will solidify and appear to have a surface tension of zero. The minimum surface tension of compressed surfactant is accepted as a major determinant of alveolar stability. The dynamic surface tension properties of surfactant obtained by saline lavage from the lungs of five babies who had died of cot death are shown in the lower part offig 1. When compressed the minimum surface tension of this surfactant was above 20 mN/m. This is very abnormal. Normal surfactant can produce low surface tensions when compressed by more than 30% of its area because it contains about 50% w/w dipalmitoylphosphatidylcholine (DPPC). If surfactant, in an alveolus, had a lower proportion of DPPC the surface area would need to be reduced proportionally more before it produced a surface tension low enough to stabilise the alveoli. As a consequence the alveolar volume at end expiration would probably be smaller. In some situations the composition of the surfactant may be so abnormal that it does not produce low surface tensions when compressed. Under such circumstances, a reduction in the size of the alveolus may precipitate rapid alveolar collapse. However,
1330 examination. The wound was irrigated with hydrogen peroxide and antibiotics and left exposed. There was no exudate and the muscles looked healthy. Microscopy and culture did not reveal clostridia. The patient’s temperature, pulse, and respiratory rate returned to normal within 24 hours and he was discharged from intensive care
the 6th postoperative day. The rapid recovery of this patient and the negative bacteriological examinations make a diagnosis of gas gangrene unlikely. However, retrograde air injection from the suction unit could explain the surgical emphysema. The drain used is a 775 ml graduated suction drainage unit, fitted with a non-return valve which closes automatically during compression of the container. However the valve in the unit used was defective and there was retrograde air flow during compression of the container. This hazard can be avoided by completely occluding the tube manually with the side clamp before compression of the suction unit.
on
tension/area
2-Surface Fig phosphatidylcholines.
loops
for
mixtures
of
DPPC-dipalmitoylphosphatidylcholine; EggPC =unsaturated phosphatidylcholine. subphase
at
Traces superimposed. Experiments done separately 37 °C. Lipid mixtures were spread from solvents.
on
saline
alveoli are supported by other mechanisms (ie, tissue forces) so that large, contractile forces across the alveolar wall would predispose to alveolar oedema. The surfactant obtained from the lungs of infants dying a cot death has levels of DPPC lower than normal. Fig 2 illustrates the effect of reducing the amount of DPPC in an artificial surfactant system. Clearly, the lower the proportion of DPPC the higher the minimum surface tension of the compressed film. These results show that babies who have died from cot death and had abnormal surfactant were vulnerable to a sudden reduction in alveolar volume and alveolar oedema.
In respiratory diseases where alveoli are- likely to collapse, expiration becomes prolonged and active against a partly closed glottis. This maintains a positive pressure in the airways which
preventsreduction in the alveolar size. If, during
an
active
expiration, the surfactant was abnormal and the larynx relaxed the alveolar volume would fall, resulting in sudden hypoxia. The only mechanism which could prevent sudden death would be gasping and a restoration of laryngeal function. Perhaps babies with abnormal surfactant who die suddenly are unable to do this. Department of Paediatrics, University of Cambridge Clinical School, Addenbrooke’s Hospital, Cambridge CB2 2QQ
C. J. MORLEY R. J. DAVIES C. M. HILL
Department of Veterinary Medicine, Addenbrooke’s Hospital, Cambridge CB2 2QQ
M. E. HEATH
1.
Morley CJ, Hill CM, Brown BD, Barson AJ, Davis JA. Surfactant abnormalities in babies dying from sudden infant death syndrome. Lancet 1982; i: 1320-23.
SURGICAL EMPHYSEMA FROM WOUND DRAINAGE SUCTION UNIT
SIR,-A 25-year-old man injured in a road-traffic accident bad signs of internal haemorrhage with a fracture of the left femur and compound fractures of the right tibia and fibula. Laparotomy revealed a huge retroperitoneal haematoma which was drained. The left femur was fixed with an intramedullary nail. Three units of cross-matched blood were given during the operation. Two suction drains (’Red-O-Pak’; Vygon) were inserted in the left thigh. General anaesthesia was uneventful and the patient was transferred to intensive care in a stable condition. 14 hours after surgery the patient became irritable, with tachypnoea and tachycardia, and his temperature rose from normal to 38-5° C. Surgical emphysema of the left thigh was detected by palpation and by X-ray. The sudden change in the patient’s condition and the presence of gas in traumatised tissue suggested gas gangrene, and 2 megaunits of crystalline penicillin and 50 000 IU gas gangrene antitoxin were given intravenously. The left thigh wound was reopened and swabs were taken for bacteriological
King Faisal University, King Fahd Hospital, PO Box 2208, Al-Khobar 31952, Saudi Arabia
MOHAMED NAGUIB MOHAMED ABDULLATIF HENRY K. GYASI
ANTIBODIES TO SIMIAN T-LYMPHOTROPIC RETROVIRUS TYPE III IN AFRICAN GREEN MONKEYS AND RECOGNITION OF STLV-III VIRAL PROTEINS BY AIDS AND RELATED SERA
SIR,-Unlike AIDS in the Western world, the disease in central Africa does not seem preferentially to afflict previously defined high-risk groups. HTLV-III/LAV is thought to play a role in the causation of AIDS. Retrospective studies indicate the presence of HTLV-III or a related agent in Uganda as early as 19721 and HTLV-I may also have come from Africa.2 One theory is that the agent causing AIDS originated in Africa. An HTLV-I related virus found in African and Asian Old World primates3,4 has in-vitro characteristics, viral proteins, and genetic structure resembling those of HTLV-1 and has been associated with spontaneous lymphoma in three species of macaque, paralleling clinical reports of a link between HTLV-I and adult T-cell leukaemia/lymphoma.We have isolated, serologically identified, and characterised another type C retrovirus of rhesus macaques, this one more closely related to HTLV-III.6,7 This virus (simian T-lymphotropic virus type III, STLV-III) possesses growth characteristics, ultrastructural morphology, and viral proteins similar to those of HTLV-III. STLV-III was isolated from four diseased macaques, three with immunodeficiency syndrome and one with transmitted lymphoma. Rhesus macaques are indigenous to areas of Asia where few cases of AIDS have been reported so, as a preliminary test of the possibility that an HTLV-III related virus in Old World primates might have been transmitted to man, we sought evidence for an HTLV-III related virus in Old World primates from areas of Africa associated with human AIDS. We studied sera from three non-human primates known to inhabit central Africa-namely, wild-caught African green monkeys (Cercopithecus aethiops) and captive chimpanzees (Pan troglodytes) and baboons (Papio anubis, P cynocephalus, and P hamadryas). Human sera positive for HTLV-III antibodies were collected from patients with AIDS or AIDS-related complex and from healthy homosexuals. HTLV-III seronegative cancer patients served as controls. Sera were subjected to (RIP) and gel electrophoresis (see legend to figure)7, with 35S-cysteine whole cell lysate prepared from Hut 78/STLV-III, a stable producer of STLV-III. Uninfected Hut 78 cells were similarly prepared, this being a well characterised human mature T cell line. Sera were prescreened for antibodies to STLV-III by membrane immunofluorescence (MIF).8,9 The 160, 120, 55, and 24 kD viral antigens of STLV-III (figure) were immunoprecipitated by both MIF-positive macaque sera and by HTLV-III positive sera from patients with AIDS or AIDSrelated complex. Monoclonal antibody directed to p24 (the major core antigen of HTLV-III) recognised a 24 kD species on STLV-III infected Hut 78 but not on uninfected Hut 78. MIF-positive African green monkey sera recognised the same STLV-III proteins but chimpanzee or baboon MIF-negative sera did not.
radioimmunoprecipitation
by abdominal discomfort and, in two cases, increases in pancreatic enzymes (all reproducible on re-challenge). In one published case of suspected alveolitis after nomifensine chest X-rays did not suggest altered lung structure, and lung function studies and biopsy were not done.2Two cases are mentioned in another study but without any details. 10 We conclude that nomifensine is a drug capable of inducing hypersensitivity alveolitis. Progression towards lung fibrosis cannot yet be excluded.
,
H. HAMM 1st Medical
Department,
J. AUMILLER
Marienkrankenhaus Hamburg, 2 Hamburg 76, West Germany
R. BÖHMER H. P. MISSMAHL
Israelitisches Krankenhaus Hamburg
U. FÜLLBRANDT H. FRENZEL
1. Dankbaar
H, Mudde AH. Fever and liver function disturbances as a result oftherapy with nomifensine. Net T Geneesk 1980; 124: 2184-86. 2. Hunziker T, Fehlmann U, Kummer H, et al. Arzneifieber auf das Antidepressivum Nomifensin (Alival). Schweiz Med Wschr 1980; 110: 1295-300. 3. Nielsen JL, Lund NO. Drug fever due to nomifensine treatment in patients with endogenous depression. Int Pharmacopsychiat 1981; 16: 66-68. 4. Brandes JW, Körst HA, Littmann KP. Gelbsucht nach Nomifensin. Med Welt 1980; 31: 1607-08. 5. Eckstein R, Riess H, Sauer H, Mempel W. Nomifensine-induced immune haemolytic anaemias. Klin Wschr 1981; 59: 567-69. 6. Bournerias F, Habibi B. Nomifensine-induced immune haemolytic anaemia and impaired renal function. Lancet 1979; ii: 95-96. 7. Lyloff K, Jersild C, Bacher T, Slot O. Massive intravascular haemolysis during treatment with nomifensine. Lancet 1982; ii: 41. 8. Prescott LF, Illingworth RN, Critchley JAJH, et al. Acute haemolysis and renal failure after nomifensine overdosage. Br Med J 1980; 281: 1392-93. 9. Garcia-Morteo O, Maldonado-Cocco JA. Lupus-like syndrome during treatment with nomifensine. Arthritis Rheum 1983; 26: 936. 10. Wälti M, Neftel K, Cohen M, De Weck AL, Perisic M. Nachweis von arzneimittelspezifischen IgE- und IgG-Antiköpern mittels RIA: klinische Bedeutung am Beispiel Nomifensin (Alival). Schweiz Med Wschr 1983; 113: 1865-67.
LEGIONNAIRES’ DISEASE IN STAFFORDSHIRE
SIR,-A 66-year-old man was admitted to Stafford General Infirmary on April 6, 1985. After 4 days as an inpatient on the top floor of the hospital he went to his son’s house in Huntingdon to convalesce (from a fractured sternum). He returned to Bradford on April 18, but on the journey home became delirious and had He was admitted to a local hospital and transferred the following day where the triad of mental confusion, gastroenteritis, and pneumonia suggested a diagnosis of legionnaires’ disease and erythromycin was started. The patient made an uneventful recovery. The initial legionella titre was below 1:8 but by May 8 the titre had risen three-fold. Any patient with atypical pneumonia should be treated with erythromycin without waiting for serological confirmation. Adherence to this policy led to the correct treatment of another case of legionnaires’ disease in this hospital, this one having no link with the Staffordshire epidemic. Talk of mystery viruses and undiscovered diseases misleads.
gastroenteritis. to
St Luke’s
Medical Unit, St Luke’s Hospital, Bradford BD5 0NA
on
J. R. STANILAND C. GLEW
J. PECHAN
ALVEOLI AND ABNORMAL SURFACTANT
SIR,-Dr Talbert and Dr Southall (March 30, p 727) suggest that alveoli lined with abnormal surfactant may collapse if their size is reduced below a critical radius determined by the minimum surface tension of the surfactant film. Their mathematical model is based on the assumption that alveoli are spheres lined with surfactant. However, alveoli are neither closed nor spherical, and during breathing little is known of how their area and shape change. They may shrink or convolute like a plastic bag, and probably they do both. The radius of the alveoli and the way in which this changes with volume will critically affect any mathematical model. Without details of alveolar shape and area it is not possible to construct an accurate mathematical model to explain
Fig I-Surface tensionlarea loop for surfactant at 37OC. Upper: lipid extract from human amniotic fluid (normal). Lower: lipid extracts of surfactant from five babies who died from cot death on 0 9% saline, spread dry.
the role of a defective surfactant in alveolar mechanics. It is also necessary to understand the surface properties during compression of "defective" surfactant. We present below some surface tension data collected on surfactant obtained from infants who have died suddenly and unexpectedly (cot death). When rapidly compressed at body temperature, normal surfactant will always reduce surface tension below 10 mN/m (fig 1). Often the film will solidify and appear to have a surface tension of zero. The minimum surface tension of compressed surfactant is accepted as a major determinant of alveolar stability. The dynamic surface tension properties of surfactant obtained by saline lavage from the lungs of five babies who had died of cot death are shown in the lower part offig 1. When compressed the minimum surface tension of this surfactant was above 20 mN/m. This is very abnormal. Normal surfactant can produce low surface tensions when compressed by more than 30% of its area because it contains about 50% w/w dipalmitoylphosphatidylcholine (DPPC). If surfactant, in an alveolus, had a lower proportion of DPPC the surface area would need to be reduced proportionally more before it produced a surface tension low enough to stabilise the alveoli. As a consequence the alveolar volume at end expiration would probably be smaller. In some situations the composition of the surfactant may be so abnormal that it does not produce low surface tensions when compressed. Under such circumstances, a reduction in the size of the alveolus may precipitate rapid alveolar collapse. However,
1330 examination. The wound was irrigated with hydrogen peroxide and antibiotics and left exposed. There was no exudate and the muscles looked healthy. Microscopy and culture did not reveal clostridia. The patient’s temperature, pulse, and respiratory rate returned to normal within 24 hours and he was discharged from intensive care
the 6th postoperative day. The rapid recovery of this patient and the negative bacteriological examinations make a diagnosis of gas gangrene unlikely. However, retrograde air injection from the suction unit could explain the surgical emphysema. The drain used is a 775 ml graduated suction drainage unit, fitted with a non-return valve which closes automatically during compression of the container. However the valve in the unit used was defective and there was retrograde air flow during compression of the container. This hazard can be avoided by completely occluding the tube manually with the side clamp before compression of the suction unit.
on
tension/area
2-Surface Fig phosphatidylcholines.
loops
for
mixtures
of
DPPC-dipalmitoylphosphatidylcholine; EggPC =unsaturated phosphatidylcholine. subphase
at
Traces superimposed. Experiments done separately 37 °C. Lipid mixtures were spread from solvents.
on
saline
alveoli are supported by other mechanisms (ie, tissue forces) so that large, contractile forces across the alveolar wall would predispose to alveolar oedema. The surfactant obtained from the lungs of infants dying a cot death has levels of DPPC lower than normal. Fig 2 illustrates the effect of reducing the amount of DPPC in an artificial surfactant system. Clearly, the lower the proportion of DPPC the higher the minimum surface tension of the compressed film. These results show that babies who have died from cot death and had abnormal surfactant were vulnerable to a sudden reduction in alveolar volume and alveolar oedema.
In respiratory diseases where alveoli are- likely to collapse, expiration becomes prolonged and active against a partly closed glottis. This maintains a positive pressure in the airways which
preventsreduction in the alveolar size. If, during
an
active
expiration, the surfactant was abnormal and the larynx relaxed the alveolar volume would fall, resulting in sudden hypoxia. The only mechanism which could prevent sudden death would be gasping and a restoration of laryngeal function. Perhaps babies with abnormal surfactant who die suddenly are unable to do this. Department of Paediatrics, University of Cambridge Clinical School, Addenbrooke’s Hospital, Cambridge CB2 2QQ
C. J. MORLEY R. J. DAVIES C. M. HILL
Department of Veterinary Medicine, Addenbrooke’s Hospital, Cambridge CB2 2QQ
M. E. HEATH
1.
Morley CJ, Hill CM, Brown BD, Barson AJ, Davis JA. Surfactant abnormalities in babies dying from sudden infant death syndrome. Lancet 1982; i: 1320-23.
SURGICAL EMPHYSEMA FROM WOUND DRAINAGE SUCTION UNIT
SIR,-A 25-year-old man injured in a road-traffic accident bad signs of internal haemorrhage with a fracture of the left femur and compound fractures of the right tibia and fibula. Laparotomy revealed a huge retroperitoneal haematoma which was drained. The left femur was fixed with an intramedullary nail. Three units of cross-matched blood were given during the operation. Two suction drains (’Red-O-Pak’; Vygon) were inserted in the left thigh. General anaesthesia was uneventful and the patient was transferred to intensive care in a stable condition. 14 hours after surgery the patient became irritable, with tachypnoea and tachycardia, and his temperature rose from normal to 38-5° C. Surgical emphysema of the left thigh was detected by palpation and by X-ray. The sudden change in the patient’s condition and the presence of gas in traumatised tissue suggested gas gangrene, and 2 megaunits of crystalline penicillin and 50 000 IU gas gangrene antitoxin were given intravenously. The left thigh wound was reopened and swabs were taken for bacteriological
King Faisal University, King Fahd Hospital, PO Box 2208, Al-Khobar 31952, Saudi Arabia
MOHAMED NAGUIB MOHAMED ABDULLATIF HENRY K. GYASI
ANTIBODIES TO SIMIAN T-LYMPHOTROPIC RETROVIRUS TYPE III IN AFRICAN GREEN MONKEYS AND RECOGNITION OF STLV-III VIRAL PROTEINS BY AIDS AND RELATED SERA
SIR,-Unlike AIDS in the Western world, the disease in central Africa does not seem preferentially to afflict previously defined high-risk groups. HTLV-III/LAV is thought to play a role in the causation of AIDS. Retrospective studies indicate the presence of HTLV-III or a related agent in Uganda as early as 19721 and HTLV-I may also have come from Africa.2 One theory is that the agent causing AIDS originated in Africa. An HTLV-I related virus found in African and Asian Old World primates3,4 has in-vitro characteristics, viral proteins, and genetic structure resembling those of HTLV-1 and has been associated with spontaneous lymphoma in three species of macaque, paralleling clinical reports of a link between HTLV-I and adult T-cell leukaemia/lymphoma.We have isolated, serologically identified, and characterised another type C retrovirus of rhesus macaques, this one more closely related to HTLV-III.6,7 This virus (simian T-lymphotropic virus type III, STLV-III) possesses growth characteristics, ultrastructural morphology, and viral proteins similar to those of HTLV-III. STLV-III was isolated from four diseased macaques, three with immunodeficiency syndrome and one with transmitted lymphoma. Rhesus macaques are indigenous to areas of Asia where few cases of AIDS have been reported so, as a preliminary test of the possibility that an HTLV-III related virus in Old World primates might have been transmitted to man, we sought evidence for an HTLV-III related virus in Old World primates from areas of Africa associated with human AIDS. We studied sera from three non-human primates known to inhabit central Africa-namely, wild-caught African green monkeys (Cercopithecus aethiops) and captive chimpanzees (Pan troglodytes) and baboons (Papio anubis, P cynocephalus, and P hamadryas). Human sera positive for HTLV-III antibodies were collected from patients with AIDS or AIDS-related complex and from healthy homosexuals. HTLV-III seronegative cancer patients served as controls. Sera were subjected to (RIP) and gel electrophoresis (see legend to figure)7, with 35S-cysteine whole cell lysate prepared from Hut 78/STLV-III, a stable producer of STLV-III. Uninfected Hut 78 cells were similarly prepared, this being a well characterised human mature T cell line. Sera were prescreened for antibodies to STLV-III by membrane immunofluorescence (MIF).8,9 The 160, 120, 55, and 24 kD viral antigens of STLV-III (figure) were immunoprecipitated by both MIF-positive macaque sera and by HTLV-III positive sera from patients with AIDS or AIDSrelated complex. Monoclonal antibody directed to p24 (the major core antigen of HTLV-III) recognised a 24 kD species on STLV-III infected Hut 78 but not on uninfected Hut 78. MIF-positive African green monkey sera recognised the same STLV-III proteins but chimpanzee or baboon MIF-negative sera did not.
radioimmunoprecipitation